Peptide microparticle compositions and related methods

Abstract

The invention herein provides pharmaceutically acceptable, controlled-release particulate compositions and formulations comprising such compositions for the treatment of obesity, diabetes, or both. The compositions and formulations herein comprise particulates containing an API and a biodegradable polymer compound. The API of the compositions and formulations herein exhibits detectable or significant agonist activity against one or more of the following: melanocortin-1 receptor (MC1), melanocortin-2 receptor (MC2), melanocortin-3 receptor (MC3), melanocortin-4 receptor (MC4), and melanocortin-5 receptor (MC5), GLP-1 receptor, glucagon receptor, and GIP receptor, and generally has a molecular weight of at least about 1000 Da.

Description

TECHNICAL FIELD

[0001] The present invention relates generally to stable, long-acting, release microparticle (e.g., microsphere) formulations containing a melanocortin receptor agonist active pharmaceutical ingredient or (structurally, functionally, or both) analogous / related API molecule or an incretin hormone agonist active pharmaceutical ingredient or (structurally, functionally, or both) analogous / related API molecule, or a combination thereof, the melanocortin receptor agonist active pharmaceutical ingredient or analogous / related API molecule being an agonist of one or more of melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), or melanocortin-5 (MC5) receptors, the incretin hormone agonist active pharmaceutical ingredient or analogous / related API molecule being an agonist of one or more of glucagon-like peptide-1 (GLP-1), glucagon receptor, glucose-dependent insulinotropic polypeptide (GIP), and methods of use of the foregoing formulations in the treatment of obesity. BACKGROUND

[0002] Overweight ("excess weight") and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health. Body mass index (BMI) over 25 is considered overweight, and over 30 is considered obese. The problem of excess weight and obesity has developed to the extent of an epidemic worldwide, with over 4 million people dying each year from excess weight or obesity (2017 data). As of the filing of this application, in every region except Sub-Saharan Africa and Asia, the number of obese people exceeds the number of underweight people. Excess weight and obesity, once considered a problem only in high-income countries, are now rising sharply in low- and middle-income countries, especially in urban settings. The vast majority of overweight or obese children live in developing countries, with growth rates over 30% higher than in developed countries.

[0003] Excess weight and obesity are major risk factors for many chronic diseases, including cardiovascular disease (e.g., heart disease and stroke), which are leading causes of death globally. Excess weight can lead to musculoskeletal disorders, including osteoarthritis, and obesity is also associated with certain cancers, including endometrial, breast, ovarian, prostate, liver, gallbladder, kidney, and colon cancers.

[0004] While other factors are involved, the root cause of obesity is an imbalance between the calories consumed and the calories expended. With changes in global diets over the last few decades, there has been an increase in the consumption of energy-dense foods that are high in fat and free sugars. Physical activity has also decreased due to changes in the nature of many types of work, greater access to motorized transport, and an acceleration of the urbanization process.

[0005] Type 2 diabetes occurs primarily due to obesity and lack of exercise. Some people are genetically more at risk than others. Type 2 diabetes accounts for approximately 90% of diabetes cases, with the remaining 10% primarily attributed to Type 1 diabetes and gestational diabetes. Thus, being overweight can lead to diabetes and related conditions, including blindness, limb complications (often leading to amputation), and the need for dialysis. Since 1980, the incidence of diabetes worldwide has quadrupled. Even if an individual is only slightly overweight, the risk of the above diabetes and other non-communicable diseases increases and becomes more severe as the body mass index (BMI) climbs.

[0006] In addition to dietary changes and exercise, current such treatment regimens involve weekly subcutaneous administration of a pharmaceutical product, such as the FDA-approved semaglutide (WEGOVY) injection, which is used for chronic weight management in adults with obesity or overweight status and at least one weight-related condition.

[0007] Recently, the FDA also approved tirzepatide (MOUNJARO TM ) once-weekly subcutaneous injection for improving glycemic control in adult patients with type 2 diabetes, and ZEPBOUND TM (tirzepatide) once-weekly subcutaneous injection as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults.

[0008] Tirzepatide is a GIP receptor and GLP-1 receptor agonist. It contains a C20 fatty diacid that enables binding to albumin and prolongs half-life. Tirzepatide selectively binds to and activates GIP and GLP-1 receptors, the targets of native GIP and GLP-1. Tirzepatide enhances first- and second-phase insulin secretion and reduces glucagon levels, both in a glucose-dependent manner.

[0009] GLP-1 is a physiological regulator of appetite and caloric intake. Nonclinical studies suggest that the addition of GIP can further contribute to the regulation of food intake. Both GIP and GLP-1 receptors are present in brain regions involved in appetite regulation. Animal studies suggest that tirzepatide is able to distribute to and activate neurons in brain regions involved in the regulation of appetite and food intake.

[0010] Semaglutide (IMCIVREE®) once-daily subcutaneous injection is another FDA-approved product for chronic weight management.

[0011] The MC4 receptor in the brain is involved in the regulation of hunger, satiety, and energy expenditure. Based on nonclinical evidence, in obese patients with BBS associated with POMC, PCSK1, or LEPR deficiency or insufficient MC4 receptor activation, seminotide can re-establish MC4 receptor pathway activity to reduce food intake and promote weight loss by reducing calorie intake and increasing energy expenditure.

[0012] Various methods for addressing burst release have been proposed by those skilled in the art, such as embedding ionic groups, fatty acids, or amines into microspheres of such compositions. These methods result in the injection of these additional compounds into the human body, and therefore, potential toxicity assessments must be considered and conducted. Lee's WO01 / 78687 describes a composition comprising biodegradable porous microspheres (with accessible ionic functional groups) and a biopharmaceutical incorporated therein, as well as a method for preparing the composition. Zats' US2023 / 0014750 describes a smegglutide reservoir formulation for the treatment of type 2 diabetes, obesity, and Parkinson's disease.

[0013] All products used to treat weight management, obesity, and type 2 diabetes are administered daily or weekly. Frequent injections are inconvenient for patients. Currently, there are no commercially available products offering burst-release-limited, controlled-release of the active pharmaceutical ingredient to treat the growing global population of people with diabetes and obesity. Providing such a product while avoiding the administration of additional compounds as components of such compositions would require highly inventive inventive concepts. Definitions and terms (Definition principles and description of selected terms)

[0014] This section provides guidance and resources designed to help readers understand the contents of this disclosure. General terms and principles

[0015] The target audience (“readers”) of this disclosure is persons with at least ordinary skills in the technical practices discussed or used herein. Readers may also be referred to as “technical personnel,” and such technology and related publicly available prior knowledge are collectively referred to as “prior art.” Terms such as “understood,” “known,” and “general meaning” refer to the general knowledge of a technical person.

[0016] The purpose of this document (“Disclosure”) is to describe several new technologies (sometimes simply referred to as “technology”, and each discrete implementation thereof is sometimes referred to as “a technology”) and to provide the reader with the ability to practice such technologies (e.g., by illustration, by describing their elements and the relationships between such elements, and other possible methods). The reader will understand from this disclosure whether the technology / these technologies include different forms, such as objects (e.g., systems, compositions, or devices), methods, or both, as will become clear from this disclosure. The disclosed technology may be associated with surprising, unexpected, or other inventive features; therefore, in many cases, the described technology may reflect an invention.

[0017] The term “in the absence of contradiction” means that it is not contradicted by the content, logic, or reasonableness of this disclosure, the latter two elements being based on the knowledge of a person skilled in the art.

[0018] This document discloses several different but related exemplary aspects (variations) of the technology (also referred to, for example, as “situation,” “side,” “aspect,” or “implementation”). This disclosure covers all such individually described aspects as well as all such aspects that can be obtained through any combination of such individual aspects. Therefore, unless otherwise specified, any reference to “aspect” (e.g., “according to some aspects” or “in one aspect”) shall be understood to refer to any other suitable aspect of the technology described herein. In this respect, the breadth and scope of this disclosure should not be limited by any exemplary aspect / implementation herein. No language in this disclosure should be construed as indicating that any element / step is essential for practicing any technology or group of technologies provided by this disclosure, unless such a requirement is expressly stated. Unless otherwise specified, any aspect described in any part of this disclosure may be combined with any other aspect in any other part. The reader will discern that the term “aspect” is sometimes also used to refer to a part of this disclosure, and in this respect, its use is similar to that of “subject” or “topic.”

[0019] Unless otherwise specified, all technical / scientific terms used herein should be interpreted, at least in one respect, as having the same meaning as commonly understood by one of ordinary skill in the art, regardless of any narrower examples or descriptions provided herein (including any terms initially introduced in quotation marks). However, the reader will also recognize that some aspects may be characterized by including elements, steps, features, characteristics, etc., associated with a particular description provided herein, and such particular disclosure represents different implementations of this disclosure, unlike the corresponding aspects provided by interpreting the relevant aspects using any broader, commonly used terms or concepts. Unless otherwise specified, the use of known terms that are defined by example or otherwise implicitly disclose one or more relevant aspects in which the applicable terms are interpreted, alternatively, using the broadest reasonable interpretation by one of ordinary skill in the art.

[0020] Where there is no contradiction, the term “or” here means “and / or”, regardless of whether the actual phrase “and / or” is included (e.g., the phrases “A, B or C” and “A, B and / or C” each simultaneously disclose aspects including: (1) all of A, B, and C; (2) A and C; (3) A and B; (4) B and C; (5) A only; (6) B only; and (7) C only (and also supports subgrouping, such as “A or B”, “A or C”, etc.)). Where there is no contradiction, the use of modifiers / terms such as “or both” in association with an element (e.g., “element A, element B, or both”) does not imply or suggest that an element listed only as “A or B” does not include combinations of A and B.

[0021] For the sake of brevity, symbols are used where appropriate. For example, “&” is used for “and”, and “~” for “about”. Symbols such as < and > are given their ordinary meanings (e.g., “≤” means “less than or equal to” and “≥” means “greater than or equal to”). The slash “ / ” between terms in this document may indicate “or” (“A / B” means “A or B”) or a synonym for an element based on the context. The inclusion of “(s)” after an element or step indicates the presence of ≥1 such element, the execution of a step, etc. For example, “element(s)” refers to both 1 element and ≥2 elements, and each of them is understood to be an independent aspect of this disclosure.

[0022] Where there is no contradiction, the term "also" means "also or alternatively." Where there is no contradiction, the terms "here" and "this article" mean "within this disclosure." The abbreviation "ia" (alternately "ia" or "ia") means "other than" or "(possibly) among other things." "Also known as" is abbreviated as "aka," "AKA," or "aka" (and may also or alternatively mean "referred to herein in other ways," even if the relationship between the terms is not well known). The similar abbreviation "aka / ac" means "also known as or otherwise," and is sometimes used alternatively to emphasize this point regarding the nature of the abbreviation. Where there is no contradiction, the term "elsewhere" means "elsewhere in this article."

[0023] In the context of a list of elements / steps, the abbreviation “etc.” (or “etc.”) refers to any or all suitable combinations of the said elements / steps or any known equivalents known in the art for implementing the function of such elements / steps. Readers should similarly interpret phrases such as “such as”.

[0024] Unless otherwise specified, terms such as “and combinations,” “or combinations,” and “combinations thereof” relating to the listed elements / steps mean any or all possible / suitable combinations of the relevant elements / steps. Thus, for example, unless otherwise specified, phrases such as “any of these combinations” refer to any or all combinations.

[0025] An aspect may be described as suitable for the methods / uses disclosed herein. Unless otherwise specified, terms such as “suitable” or “appropriate” mean acceptable, appropriate, or practical in some respects for performing a particular function / achieving a particular state / result, and generally mean effective, practical, and harmless / non-harmful to the relevant valuable subject matter (human health, resource status, etc.). For example, unless otherwise specified, the term “suitable” means appropriate, acceptable, or sufficient in the context, or provides at least generally or substantially all (of the elements or the whole of the aspect) of the intended function without causing or conferring significant negative / harmful effects. Unless otherwise specified, each method step, component / ingredient, or result element of the technical aspects of this disclosure should be understood as implicitly being primarily, substantially only, essentially only, or only a suitable amount, degree, or characteristic associated with its intended function, the intended function of the relevant whole, or both. In some respects, fitness can be demonstrated through scientific research and achieved to a significant degree through appropriate tests / measures such as scientific testing, well-controlled and adequate research (e.g., clinical studies), and trials with sufficiently large efficacy.

[0026] Steps, elements, compositions, devices, components, etc., may or may alternatively be characterized as “effective.” Without contradiction, any disclosed element shall be interpreted as effective for its intended purpose and present in an effective quantity, and any performed step shall be understood as being effectively performed / applied, for example, in an effective quantity or effective number of times. Without contradiction, efficacy can be judged by assessing the ability of the element to perform or facilitate the said function or characteristic associated with the component, device, step, etc., the overall aspect, or both, in any manner or both disclosed herein and known in the prior art. For example, when applied to effects in organisms (such as humans), efficacy and similar terms shall, without contradiction, be interpreted as disclosing at least implicitly an efficacy that can be measured in: (1) among treated subjects, (2) among the majority of subjects in a population, (3) among a statistically significant number of subjects in a population, (4) among substantially all subjects in a population, (5) among essentially all subjects in a population, or (6) among a statistically significant number or more of typical or average subjects of the treated subject categories. Where there is no contradiction, an object element or step is understood to exist implicitly in an “effective quantity,” and, where there is no contradiction, any described category of object or step associated with an apparatus, system, composition, or method is understood to exist in the relevant whole or to be performed in connection with the relevant whole method in an effective quantity, in an effective manner, or with effective characteristics. This generally means that the described object / component or step is an effective quantity for the function associated with that element, the relevant whole, or both. “Step” is not necessarily a general “step” for performing a function.

[0027] Unless otherwise specified, the headings (e.g., "Definitions and Terminology") and subheadings used herein are for convenience and do not limit the scope of any aspect. Unless otherwise specified, an aspect, step, or element described under one heading may apply to other aspects or steps / elements herein.

[0028] The numerical ranges described herein represent every value falling within the range at the smallest endpoint without explicitly stating each value of the range. For example, the range 1–2 implicitly discloses each of 1.0, 1.1, 1.2, … 1.9, and 2.0, and 10–100 implicitly discloses each of 10, 11, 12, … 98, 99, and 100. Without contradiction, all ranges include the endpoints of the range, regardless of how the range is described. For example, “between 1 and 5” includes 1 and 5 in addition to 2, 3, and 4 (and all such numbers within the order of magnitude of such endpoints, e.g., 1.0, 1.1, … 4.9, and 5.0). For the avoidance of doubt, any number within a range, regardless of its order of magnitude, is included within the range (e.g., the range 2–20 includes 18.593). Without contradiction, the reader will understand that any two values ​​in the range provided herein as a list can be combined as endpoints to form a range that defines a more specific aspect of this disclosure (e.g., if a list of values ​​1, 2, 3, 4, and 5 for element X is provided, the reader will understand that this disclosure implicitly discloses aspects including 2-4 X, 3-5 X, and 1-3 X, etc.).

[0029] Terms of approximation (e.g., “about / approximately”) may be used herein to (1) refer to a set of related values ​​or (2) when precise values ​​are difficult to define (e.g., due to limitations of measurement). Where there is no contradiction, all precise values ​​provided herein simultaneously / implicitly disclose the corresponding approximation, and vice versa (e.g., the disclosure of “about 10” provides explicit support for the exact use of 10 in that aspect / description). Ranges described with approximations include all values ​​covered by each approximation endpoint, regardless of how they are presented (e.g., “about 10-20” has the same meaning as “about 10-about 20”). The range of values ​​covered by approximation terms generally depends on the context of the disclosure, its criticality or operability, statistical significance, understanding of the prior art, etc. In the absence of guidance on a particular element in this document or the prior art, terms such as “about”, when used in connection with that element, should be interpreted as ±10% of the value shown, and implicitly disclose ±5%, ±2%, ±1%, and ±0.5%. If two or more values ​​are considered to be approximately the same on this basis, they can be characterized as approximately similar.

[0030] Aspects may be associated with descriptions of change or difference. In some cases, similarity or difference may be assessed as similar or dissimilar (i.e., statistically similar or different). In some cases, difference or change means “considerable” change or difference, which means beyond what would be considered substantially the same or approximately the same (in such contexts, approximation or about is either defined in the prior art or defined as + / - 10%, or is considered by the reader to have no substantially different characteristics or results in terms of the intended function) (e.g., change ≥12.5%, ≥15%, ≥20%, etc., such as 12.5%-50%, 12.5%-33%, 15-45%, etc., or 15-150%, 20-200%, 30-300%, etc.). In some respects, a change or difference in an element may be characterized as a “major” change or difference, which means that the change or difference is (1) an increase or decrease of at least 33%, and may be a change of at least 50%, at least 75%, at least 100%, at least 150%, at least 200% (2x), for example, at least 0.5x-5x, 10x, or 20x, or (2) an increase or decrease of one or more (e.g., 2 or 3) orders of magnitude. Where there is no contradiction, elements, compositions, results, etc., described herein as different or in any of these ways as different provide implicit support for the corresponding aspect in which the applicable change / difference is characterized as one of the other differences. The modifier “constrained” means that a value, such as a considerable value, a detectable value, or a major value, is constrained to 50% or less of the whole (e.g., 45% or less, 40% or less, 37.5% or less, or 35% or less of the whole). Where there is no contradiction, the disclosure of any such term in this document provides implicit support for other corresponding aspects in which the range of applicable values ​​can be characterized as constrained values.

[0031] This disclosure includes technical aspects associated with specific characteristics, such as the amount (or range) of components. In some cases, several different ranges of such characteristics may be provided. The reader will understand that each such characteristic may be associated with a specific property that distinguishes such an aspect from others, and thus each such range may be considered critical to a particular aspect of the technology, even if the related results, properties, functions, etc., associated with such an aspect are not directly / explicitly communicated in connection with any such characteristic.

[0032] For the sake of brevity, lists of aspects, elements, steps, and characteristics are sometimes used. Unless otherwise stated, each member of each list should be considered an independent aspect. Each aspect defined by any single member of the list may, and usually will, have non-obvious properties relative to aspects characterized by the other members of the list.

[0033] Where there is no contradiction, the terms “a / an” and “the” and similar designations cover both the singular and plural forms of the referenced element, step, or aspect. Where there is no contradiction, the singular form of a term herein implicitly conveys the plural form, and vice versa (in other words, disclosure of an element / step implicitly discloses a corresponding use of such / similar elements / steps, and vice versa). Thus, for example, a paragraph concerning an aspect comprising one X step supports a corresponding aspect comprising several X steps. Where there is no contradiction, the use of designations such as “a” for one element / step or characteristic and “one or more” for another element / step or characteristic in a paragraph, sentence, aspect, or claim does not alter the meaning of such designations. Thus, for example, if a paragraph describes a composition comprising “one X” and “one or more Y”, the paragraph should be understood to provide a disclosure of “one or more X” and “one or more Y”.

[0034] "Significant" and "significantly" mean that, in a given context, using ≥1 appropriate test / experiment, it is a statistically significant result / characteristic (e.g., p ≤ 0.05 / 0.01). "Detectable" means that it is measurably present / different using known detection tools / techniques. The acronym "DOS" (or "DoS") means "detectable / detectably or significantly / significantly". The term "measurably" means at a measurable level, and, without contradiction, included at a suitable measurable level / quantity. The term "detectable" provides an implicit disclosure of the aspect of "measurable", and the term "measurable" implicitly supports that the element being measured or measurable is an aspect of "detectable". Without contradiction, any aspect that includes an element described as "similar" to another element, at least as an aspect, implicitly discloses that such similarity includes statistical similarity. Without contradiction, any reference to comparisons, variations, or other relationships between elements (e.g., outcomes) characterized by similarity or detectability also implicitly discloses variations or comparisons where the differences are approximately / about the same (e.g., within + / - 10% of each other).

[0035] Unless otherwise specified, any value provided herein without a unit of measurement (e.g., weight 50 or length 20) shall either be subject to any unit previously provided for the same element / step or element / step of the same type, or, in the absence of such disclosure, to the unit most commonly associated with such element / step in the prior art.

[0036] In this document, certain measured “amounts” may be referred to or expressed as “concentrations”, and vice versa. For example, units such as weight percentage (expressed as, for example, wt.%) may be referred to as concentrations. Where there is no contradiction, the use of such units (e.g., wt.%) should be understood to have the meaning commonly understood in the prior art, whether such units are referred to as concentrations or amounts. The reader will understand that the disclosure of the concentrations / amounts of different elements / components is a disclosure of a composition characterized by the relationship of such amounts formed between these elements / components. Therefore, where there is no contradiction, any disclosure of amounts / concentrations reflecting a suitable relationship between elements / components provides an implicit disclosure of a composition that differs from the specifically disclosed amounts / concentrations but retains that relationship. For example, if a disclosure provides that one aspect contains 1 unit of A and 3 units of B, the reader will understand that this means that the disclosure implicitly provides a corresponding aspect characterized by containing suitable amounts of A and B, wherein such amounts are present in a ratio of about 1 part A to about 3 parts B.

[0037] Unless otherwise specified, the terms “comprising,” “containing,” “including,” and “having” mean “including, but not limited to,” or “including, without limitation.” Unless otherwise specified, the use of terms such as “comprising” and “including” with respect to elements / steps means including any detectable number or quantity of elements, or including the execution of any detectable step / number of steps (with or without other elements / steps). Unless otherwise specified, “an” means one or more, even when terms such as “one or more” or “at least one” are used in conjunction with the denotation “an.”

[0038] For the sake of brevity, descriptions of aspects of a collection / whole (e.g., a system, apparatus, or composition) that include a “comprising” or “including” element implicitly support any detectable amount / quantity, such as between a detectable or measurable amount and about 33%, for example, ≥ about 1%, ≥ about 5%, ≥ about 10%, ≥ about 20%, ≥ about 25%, or ≥ about 33%, for example, about 0.00001% - about 33%, about 1% - about 33%, about 5% - about 33%, about 10% - about 33%, about 15% - about 33%, about 20% - about 33%, about 25% - about 33%, or, for example, about 30% - about 33%.

[0039] In some respects, descriptions of the set / whole in relation to the "contains" or "includes" element implicitly support quantities greater than about 33%, such as about 50% to about 75%, such as ≥ about 50%, ≥ about 51%, ≥ about 51%, ≥ about 66%, or ≥ about 70%, such as about 55% to about 75%, about 60% to about 75%, or about 70% to about 75%, such as about 35%, about 40%, or about 45%.

[0040] On a further level, the description of a set / whole in relation to the "contains" or "includes" element implicitly supports a quantity greater than about 80%, such as about 80%, about 85%, ≥ about 90%, about 93%, ≥ about 95%, ≥ about 99%, or about 100% of the whole / set is composed of the element, such as about 77% or more, or essentially all of the whole / set is composed of the element (i.e., the set is essentially composed of the referenced element). Similarly, methods described as including steps regarding effects / outcomes implicitly support the cited steps, providing ≥ about 1%, ≥ about 5%, ≥ about 10%, ≥ about 20%, ≥ about 25%, ≥ about 33%, ≥ about 50%, ≥ about 51%, ≥ about 66%, ≥ about 75%, ≥ about 90%, ≥ about 95%, ≥ about 99%, or about 100% of the effect / outcome, representing ≥ about 1%, ≥ about 5%, ≥ about 10%, ≥ about 20%, ≥ about 25%, ≥ about 33%, ≥ about 50%, ≥ about 51%, ≥ about 66%, ≥ about 75%, ≥ about 90%, ≥ about 95%, ≥ about 99%, or about 100% of the performed steps / efforts, or both. Explicit listing of percentages of elements associated with a particular aspect does not limit or refute such implicit disclosure. Where there is no contradiction, the reader should interpret terms such as “essentially all” or “essentially” as consistent with the concept of “essentially composed of…”.

[0041] Where there is no contradiction, terms such as “include” when used in connection with steps of a method provide implicit support for performing the step once, at least twice, or until the relevant function / effect is achieved.

[0042] Furthermore, the reader will understand that, without contradiction, terms such as “comprising” or “including” are used to support the premise that the cited element (or step, etc.) is “substantially” present, “essentially” present, or pre-defined. In some alternative contexts, “comprising” or “including” may refer to something that is predominantly present, approximately equal in number, or present in another quantity, such as about 40%, about 50%, etc. Thus, in some contexts, the use of “comprising” and “including” supports the premise that the cited element is present in a “significant” quantity (e.g., a statistically significant quantity) or in a DOS quantity, in a “some” quantity, or, for example, in a “dominant” quantity.

[0043] Unless otherwise specified, any disclosure of an object or method (e.g., a composition, apparatus, or system) that "comprises" or "includes" an element provides implicit support for another corresponding aspect characterized in that the object is composed of or "essentially composed of" that element (excluding anything that would "materially affect" the "fundamental and novel characteristics" of any inventive aspect of this disclosure). Unless otherwise specified, any specific use of phrases such as "composes of" and "essentially composed of" herein does not modify this principle of interpretation.

[0044] Readers will understand that the scope of the “fundamental and novel features” of the invention provided in this disclosure, and the “substantial effects” (or “material effects”) constituting such “fundamental and novel features”, will vary depending on the specific applicable aspect involved. Without contradiction, a fundamental and novel feature of any inventive aspect includes the specific described and related elements of that aspect and excludes any other element that significantly diminishes the intended function of said element, introduces a significantly new function unrelated to the intended function, significantly reduces the performance of that function, or significantly negatively alters other characteristics of performing such function (e.g., by increasing the energy, monetary, or both costs of performing that function). Without contradiction, a fundamental and novel feature also includes at least significantly preserving the suitability, effectiveness, or both of said element or aspect as a whole. Therefore, a material effect can be an effect that reduces, weakens, eliminates, offsets, cancels, or prevents one or more such functions in one or more aspects (e.g., delays onset, reduces scope, reduces duration, reduces output, reduces suitability level, reduces effect, or a combination thereof). In one aspect, a material effect is an effect that alters such a function by making it impractical, difficult to obtain, or substantially more expensive in terms of input or otherwise more costly. From this and other guidance provided in this article, the reader can understand the scope of aspects defined by what is essentially composed of a set of elements.

[0045] Where there is no contradiction, the term "a" means a single type, a single iteration / copy / thing, or both of the stated element or step, as will be clear from the context of the relevant disclosure. For example, the designation "a" used with respect to a component of a composition / article or system can refer to one type of element (which may exist in numerous copies, as in the case of an ingredient in a composition), one unit of that element, or both. Similarly, "a" component, "single" component, or "unique component" of a system generally means one type of element (which may exist in numerous copies), one instance / unit of that element, or both. Furthermore, "a" step of a method generally means one type of action (step) performed, one iteration of a step, or both. Where there is no contradiction, the disclosure of "a" element supports both, but where there is no contradiction, any claim to any "a" element means one type of such element (e.g., one type of component of a composition / system / article).

[0046] Where there is no contradiction, the term "some" means ≥2 copies / instances or ≥5% (e.g., ≥7.5%, ≥12.5%, ≥17.5%, ≥27.5%, or ≥37.5%) of the listed set / whole is or constitutes an element. Regarding methods, "some" means that ≥5% of the effect, effort, or both is constituted by or attributable to a step (e.g., in "some of the method is performed by step Y") or indicates that a step is performed ≥2 times (e.g., in "step X is repeated a certain number of times"). Terms such as "considerable amount" or "considerable portion" mean at least 1%, 2%, or 2.5%, but less than a large portion of the whole, such as 2.5-25%, e.g., 5-25%, 5-20%, 7.5-22.5%, 10-20%, 2.5-10%, 2.5-12.5%, 5-15%, etc. Terms such as “sizable portion” mean 10-50%, and in an aspect 15-50%, 20-50%, or 25-50%, or subranges thereof (e.g., 15-45%, 20-40%, 25-45%, etc.). Terms such as “primarily,” “most,” or “largely” (and “primarily” when not used to refer to the order of events or “primarily”) mean detectably >50% (e.g., “largely comprises,” “primarily includes,” etc. mean >50%) (e.g., a system that largely comprises element X is composed of >50% of element X). The term “substantially” means ≥75% (e.g., “substantially consists of,” “substantially associated with,” “substantially includes,” etc. mean ≥75%) (e.g., a method that is substantially composed of step X means that 75% of the effort or effect of the method is attributable to step X). "Substantially" or "almost" means ≥95% (e.g., "almost all," "substantially composed of," etc., all mean ≥95%) (e.g., a set consisting almost entirely of element X means that at least 95% of the elements in the set are element X). Terms such as "substantially contain" or "substantially lack" elements mean containing ≤25% of the elements, and terms such as "substantially contain" elements mean containing ≤5% of the elements. Without contradiction, any aspect described as "substantially contain" or "substantially composed of" elements implicitly discloses elements that "substantially contain" that element. The same principle applies to any disclosure in which one aspect is described as "substantially contain" elements.

[0047] Where there is no contradiction, phrases such as “substantially identical” or “substantially similar” may be used to refer to elements / components / ingredients / things (e.g., compositions, systems, devices, etc.) or steps / methods that have the same or approximately the same characteristics or generally achieve the same or approximately the same results in a similar manner, as referenced elements / things or steps / methods, or that have no meaningful difference in the expected results and the manner in which such results are achieved, or that are otherwise considered in the prior art to be no different or no substantially different in the relevant context (e.g., by being considered equivalents). Where there is no contradiction, the reader will understand that “substantially identical” or “substantially similar” elements / things or steps / methods, compared to the comparative thing / element or method / step, means that the referenced element / thing or step / method, when applied under similar conditions of use, exhibits such similar function in the same, approximately the same, or statistically similar quantities as the comparative thing or method. Again, where a statistical, approximate, or other measurement comparison is not possible, the reader will understand that the phrase covers those things known to be the same or substantially the same as the referenced element / step or as described herein.

[0048] Where there is no contradiction, any aspect describing an optional element / step also implicitly supports the corresponding aspect in which, with respect to the relevant aspect, one, some, most, substantially all, almost all, essentially all, or all of such elements are missing / steps are not performed. For example, a disclosure of a system containing element X also implicitly supports a system lacking element X. That is, the reader will understand that any element, feature, step, or characteristic of any aspect of the technology cited herein as existing in an aspect also implicitly supports the exclusion of that element, feature, step, or characteristic from the corresponding / similar aspect implied by the explicit positive disclosure, and vice versa. Where there is no contradiction, changes in tense or the way terms are presented (e.g., using "primarily contains" instead of "primarily contains") do not alter the meaning of the corresponding terms / phrases.

[0049] Unless otherwise specified, all methods provided herein can be performed in any suitable order, regardless of how they are presented (e.g., a method comprising steps A, B, and C can be performed in the order of C, B, and A; B and A, and C, performed simultaneously, etc.). Unless otherwise specified, the elements of the composition can be assembled in any suitable manner by any suitable method. In general, any methods and materials similar to or equivalent to those described herein can be used in the practice of the most extensive version of the embodiments, at least in the relevant respects. Unless otherwise specified, the use of ordinal numbers such as “first,” “second,” and “third” is primarily, although not exclusively, intended to distinguish respective elements, and not to limit the disclosure to a particular order, importance, or configuration of those elements.

[0050] Any element associated with a function is alternatively described as a “means” for performing a function or a “step” for performing part of a method in a composition / apparatus / system, and parts of this disclosure refer to “equivalents,” meaning known equivalents in the prior art for achieving the reference function associated with the disclosed means / steps. However, no element of this disclosure or claim should be construed as limited to a “means plus function” or “step plus function” structure unless such intent is clearly indicated by the use of the terms “means for…” or “step for…”. Terms such as “configured as” or “suitable” do not indicate an interpretation of “means plus function” but rather describe an element / step configured, designed as, selected as, or suitable for achieving a certain performance, characteristic, property, etc., using the teachings provided herein or in the prior art.

[0051] As used herein, the term "exemplary" means "serving as an example, instance, or illustration." Any implementation described herein as "exemplary," "representative," or "illustrative," etc., should not necessarily be construed as being more preferred or advantageous than other implementations.

[0052] Unless explicitly stated or clearly indicated by the context, terms such as “improved” or “better” mean an increase in DOS (e.g., considerably, substantially, significantly, or substantially). In some respects, as will be clear from the context or knowledge, terms such as “improved” or “better” mean a “reduction” in DOS, such as a negative aspect relating to a method or composition of reduction. Where there is no contradiction, terms such as “enhanced,” “improved,” and “better” are used synonymously.

[0053] Any reference to the trademark name (Product Trademark (™)) includes all publicly known information about the product as of the date of this application. Furthermore, references to the trademark name are intended to refer to those products that PHOSITA can identify as of the date of this application, but also to products similar to such products, such as those exhibiting biosimilarity; biologically identical products; functionally identical products (performing the same function); operationally identical products (based on the same key principles or operating through the same features); products containing the same key characteristics, components, mechanisms, etc. However, PHOSITA should recognize that simpler and alternative products may be provided than those presented herein; for example, modifications to the products described herein are included, provided that the spirit of this disclosure is maintained.

[0054] Regarding the figures, graphs, etc., disclosed in this application, such figures, graphs, etc., are exemplary, and their disclosure simultaneously provides for disclosure of anything statistically significantly similar to or “approximately” identical to the disclosed content—for example, the data provided, features / characteristics, and performance characteristics exhibited. For instance, any / all data points provided in, for example, graphs disclosed in this application include data points within a range of statistical similarity and points that are approximately the same as the exemplified ones (e.g., within a reasonable fraction of the order of magnitude). The graphs or figures provided herein should be understood to include data providing similar patterns, shapes, curves, peaks, etc., where such features are present.

[0055] All references cited herein (e.g., publications, patent applications, and patents) are incorporated herein by reference as if each reference were individually and specifically indicated to be incorporated by reference and fully elaborated herein. Where there is no contradiction, any suitable principles, methods, or elements of such references (collectively, the “Teachings”) may be combined with or applied to aspects. However, references / inclusions in patent documents are limited to their technical disclosure and do not reflect any views regarding their validity, patentability, etc. Where there is no contradiction, if there is any conflict between this disclosure and the Teachings of such documents, the content of this disclosure shall prevail in interpreting aspects of this disclosure. This document cites numerous references to concisely incorporate known information and assist those skilled in the art in putting aspects into practice. While efforts have been made to include the most relevant references for such purposes, the reader will understand that not every aspect of every cited reference will apply to every aspect of this disclosure or the art.

[0056] While elements disclosed in such incorporated references may be combined with aspects of this disclosure provided herein, the reader will understand that the described techniques are intended to be distinguished from such disclosures, and therefore, without contradiction, in some respects any element of the object or method of any such reference may be considered excluded from the scope of this presentation as a new technique (e.g., if reference A discloses object or element B, any aspect not relating to object or element B may be characterized as lacking object or element B as an aspect).

[0057] All original claims contained in this disclosure are incorporated herein by reference as if they were part of the description. Other terms, concepts, and acronyms

[0058] The following description of certain terms and acronyms is intended to help the reader understand the invention. Additional acronyms may only be provided in other parts of this disclosure, and acronyms well-known in the prior art may not be provided herein.

[0059] Unless otherwise specified, any description of weight is a weight percentage ("wt.%).

[0060] In some respects, “improved” in this article means “increased”. In other respects, “improved” means “decreased”, such as regarding, for example, fasting blood glucose levels or, for example, hemoglobin A1c levels. Where there is no contradiction, terms such as “enhanced” and “improved” are used synonymously.

[0061] "Pharmaceutical suitability" and "pharmaceutical appropriateness" are phrases commonly used to refer to a composition / formulation that is safe and effective for the administration and use of a drug, possessing sufficient potency, purity, strength, quality, and safety for drug use, as can be determined by regulatory review, and established, for example, through one or more well-controlled and adequate clinical studies conducted in accordance with generally applicable regulatory standards.

[0062] Steps, elements, devices, components, etc., may or may alternatively be described as “effective.” Without contradiction, any performed step, function of a component, etc., shall be understood as being effectively applied, for example, in an effective quantity, which in this context generally means an effective quantity for the function associated with that component, device, step, etc. Effectiveness in this respect may mean, and, without contradiction, shall be interpreted as implicitly disclosing effectiveness in: (1) among treated subjects, (2) among the majority of subjects in a population, (3) among a statistically significant number of subjects in a population, (4) among substantially all subjects in a population, (5) among essentially all subjects in a population, or (6) among a statistically significant number or more of typical or average subjects in the category of subjects with the condition to be treated (treatment in this sense encompasses any administration, application, etc., whether for therapeutic or preventative / maintenance purposes).

[0063] The excipients and other elements in the compositions described herein are generally present in “effective amounts”, and unless contradictory, any described class of excipients or other types of elements / components of a particular excipient or composition are understood to be present in the relevant composition / formulation in an effective amount, which in this context generally means an effective amount for the function associated with that excipient (it should be understood that some excipient compounds / ingredients exhibit more than one effect). For example, a tensioning agent will be understood to be present in the composition / formulation in an effective amount for imparting the indicated tension effect, the tension effect required for the suitability of the composition, or for imparting a significant tension effect to the composition (relative to a comparative composition lacking that compound / ingredient).

[0064] Readers should note that some terms specific to this field or specific to this disclosure are also or alternatively provided in the Summary / Details section or elsewhere. Without contradiction, any repetition of terms in the description is intended to reflect alternative aspects characterized by different meanings or examples of the term. Summary of the Invention

[0065] The embodiments of the invention described and claimed herein have many attributes and aspects, including, but not limited to, those set forth in the Summary of the Invention, such as those described or referenced. The Summary of the Invention (“Summary”) is not intended to be all-encompassing, and the scope of the invention is not limited to or restricted to the aspects, features, elements, or embodiments provided in the Summary of the Invention, which are included for illustrative purposes only and not for limiting purposes. Any aspect described in this section may be combined with any other aspect described in this section or with any other aspect of this disclosure.

[0066] In some aspects, the present invention provides long-acting particulate compositions and formulations for treating diabetes, obesity, or both. In some aspects, the long-acting compositions and formulations provided herein provide suitable release of the active ingredient over an extended period of time, such as at least about one month.

[0067] In some aspects, the present invention provides compositions of long-acting, injectable microparticles, wherein the microparticles comprise one or more active pharmaceutical ingredients (APIs) and a carrier. In some aspects, the one or more APIs are selected from: one or more melanocortin receptor agonists, which are agonists of one or more of melanocortin-1 receptor (MC1), melanocortin-2 receptor (MC2), melanocortin-3 receptor (MC3), melanocortin-4 receptor (MC4), and melanocortin-5 receptor (MC5); and incretin hormone agonists, which are agonists of one or more of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon receptor, and combinations thereof. In some aspects, the microparticle composition comprises microparticles, each microparticle comprising the same one or more APIs. In some aspects, the microparticle composition comprises a mixture of microparticles, wherein the mixture contains at least two microparticle subgroups, each subgroup comprising microparticles containing an API different from that of another different subgroup of microparticles.

[0068] In some aspects, the present invention provides long-acting, injectable formulations comprising a composition of microparticles containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts thereof and a carrier, wherein the one or more active pharmaceutical ingredients or pharmaceutically acceptable salts thereof are agonists of one or more of melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors, or glucagon-like peptide-1 (GLP-1); glucose-dependent insulinotropic peptide (GIP); and glucagon receptors, or any combination thereof. In some aspects, the formulation comprises a microparticle composition containing an API and a carrier, wherein sustained release of the API therefrom allows for administration at a frequency not exceeding once a month. In some aspects, the formulations provided herein exhibit detectably or significantly increased adherence due to the durability of action of a single dose compared to similar compositions or formulations requiring more frequent administration, such as compositions or formulations requiring weekly administration. In some respects, compared to similar compositions or formulations that require more frequent administration, such as compositions or formulations that require weekly administration, the single-dose duration of action of the formulations provided herein detectably or significantly reduces one or more side effects associated with the injection of such composition or formulation, one or more side effects associated with the API of such composition or formulation, or any or all of these combinations.

[0069] In some aspects, the present invention provides particulate compositions and formulations comprising such compositions as described in this section, wherein the particulates exhibit highly consistent size, shape, and maximum packing density characteristics. In some aspects, this invention provides compositions of particulates and formulations made therefrom, wherein the compositions and formulations contain an amount of any API that is not attached to, encapsulated by, incorporated into, or otherwise not associated with a carrier material (such that it can be characterized as a “free” API), such that the amount is low enough to provide a controlled release of the API during administration of the composition and formulation without exhibiting a detectable or significant burst release effect. In some aspects, a biemulsion technique is used to construct the particulate compositions to produce monodisperse microspheres of loaded peptides with limited porosity. In some aspects, the steps associated with the biemulsion technique methods described herein include suitable washing steps to leave less than about 5%, ≤4%, ≤3%, ≤2%, ≤1%, ≤0.05%, ≤0.01%, or even less of the API, or any amount of API capable of producing a burst release effect upon administration of a formulation comprising the particulate composition. In some respects, the controlled-release compositions described herein (e.g., formulations containing such compositions) may be administered once a month or even less frequently, for example, once every 3, 6, 9 or 12 months.

[0070] According to certain embodiments, the present invention provides pharmaceutically acceptable, controlled-release particulate compositions and formulations comprising such compositions for the treatment of obesity, diabetes, or both, wherein the compositions and formulations comprise particulates comprising an API and a biodegradable polymer compound. Furthermore, the compositions and formulations herein may, in some respects, exhibit detectable or significant agonist activity against one or more of the following: melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors; or glucagon-like peptide-1 (GLP-1); glucose-dependent insulinotropic peptide (GIP); and glucagon receptors, and generally have a molecular weight of at least about 1000 Da. Exemplary aspects of the present invention

[0071] The following is a non-limiting list of exemplary aspects of the invention, which illustrates embodiments of the invention in summary form to help the reader quickly understand the overall scope of the invention. Similar to the patent claims, the aspects listed in this section may reference (depend on / derive from) one or more other sections. The reader will understand that such references mean that features / characteristics or steps of such referenced aspects are incorporated / integrated into the referenced aspect. For example, if one aspect in a section (e.g., the section indicated by the text at the end of the section as aspect 2) references another aspect by one or more aspect numbers (e.g., aspect 1 or "any one of aspects 1-3"), it will be understood to include, in addition to those elements, steps, or characteristics of the referenced aspect, elements, steps, or characteristics of such referenced aspect (e.g., aspect 1) (e.g., if aspect 2 references aspect 1, it provides a description of a composition, method, system, apparatus, etc., that includes features of both aspect 1 and aspect 2).

[0072] A list describing specific exemplary embodiments of the invention is sometimes used to aid the reader in understanding the invention. Such aspects may internally reference other exemplary aspects, either individually or as a group of aspects (e.g., when such aspects are provided as a numbered list, by referring to a range within that numbered list). References to ranges of aspects should be interpreted as individually referencing all such aspects, each as a unique embodiment of the invention, and combinations of such aspects with each other, depending on the manner in which they are presented, also as unique embodiments of the invention, unless the aspects within such a referenced range are contradictory or meaningless. If a contradiction exists, references to contradictory aspects should be excluded. Composition

[0073] In a first aspect, the present invention provides a pharmaceutically acceptable, controlled-release, pharmaceutically acceptable composition comprising a microparticle population, the microparticles of the microparticle population comprising (1) one or more active pharmaceutical ingredients or pharmaceutically acceptable salts thereof, which are agonists of one or more of melanocortin-1 (MC1); melanocortin-2 (MC2); melanocortin-3 (MC3); melanocortin-4 (MC4); or melanocortin-5 (MC5) receptors, or glucagon-like peptide-1 (GLP-1); glucose-dependent insulinotropic peptide (GIP); and one or more agonists of glucagon receptors, or combinations thereof, and (2) a carrier component comprising one or more biodegradable polymers, wherein the maximum size of the microparticles in the composition in any orientation is between about 1 µm and about 120 µm; at least about 70% of the microparticles in the composition have a maximum diameter in any orientation that is within 10% of the average particle diameter in any orientation of the microparticle population; and at least about 70% of the microparticles in the composition have a maximum size in any orientation that is within 10% of the average size of the microparticles in any other orientation within the same microparticle population. (Aspect 1).

[0074] In one aspect, the present invention provides a pharmaceutically acceptable, controlled-release, pharmaceutically acceptable composition comprising a microparticle population comprising (1) one or more active pharmaceutical ingredients (APIs) selected from retatrutide, tirzepatide, setmelanotide, lixisenatide, dulaglutide, liraglutide, albiglutide, and pemvidutide, and (2) a carrier component comprising one or more biodegradable polymers, wherein the maximum size of the microparticles in any orientation is between about 1 µm and about 120 µm; at least about 70% of the microparticles in the composition have a maximum diameter in any orientation that is within 10% of the average particle diameter in any orientation of the microparticle population; and at least about 70% of the microparticles in the composition have a maximum size in any orientation that is within 10% of the average size of the microparticles in any other orientation within the same microparticle population. (Aspect 2).

[0075] In one aspect, the present invention provides a pharmaceutically acceptable, controlled-release, pharmaceutically acceptable composition comprising a microparticle population comprising (1) one or more active pharmaceutical ingredients (APIs) selected from retaglutide, telposide, sminoside, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide, and (2) a carrier component comprising one or more biodegradable polymers, wherein the maximum size of the microparticles in any orientation is between about 1 µm and about 120 µm; at least about 70% of the microparticles in the composition have a maximum diameter in any orientation that is within 10% of the average particle diameter in any orientation of the microparticle population; and at least about 70% of the microparticles in the composition have a maximum size in any orientation that is within 10% of the average size of the microparticles in any other orientation of the same microparticle population. (Aspect 3).

[0076] In one aspect, the present invention provides a pharmaceutically acceptable, controlled-release, pharmaceutically acceptable composition comprising a microparticle population comprising (1) one or more active pharmaceutical ingredients (APIs) selected from retaglutide, telposide, sminoside, lixisenatide, dulaglutide, liraglutide, abiglutide, and pervitide, and (2) a carrier component comprising one or more biodegradable polymers, wherein the maximum size of the microparticles in any orientation is between about 1 µm and about 120 µm; at least about 70% of the microparticles in the composition have a maximum diameter in any orientation that is within 10% of the average particle diameter in any orientation of the microparticle population; and at least about 70% of the microparticles in the composition have a maximum size in any orientation that is within 10% of the average size of the microparticles in any other orientation of the same microparticle population. (Aspect 4).

[0077] In some aspects, the present invention provides compositions of any one or more of aspects 1-4, wherein the composition is suitable for parenteral administration. (Aspect 5).

[0078] In some aspects, the present invention provides the composition of aspect 5, wherein the composition is administered by subcutaneous injection. (Aspect 6).

[0079] In some aspects, the present invention provides compositions of any one or more of aspects 1-6, wherein the API comprises retaglutide (aspect 7).

[0080] In some aspects, the present invention provides compositions of any one or more of aspects 1-6, wherein the API comprises telpokinesin (Aspect 8).

[0081] In some aspects, the present invention provides compositions of any one or more of aspects 1-6, wherein the API comprises semanotide (Aspect 9).

[0082] In some aspects, the present invention provides compositions of any one or more of aspects 1-6, wherein the API comprises peptidoglycan (Aspect 10).

[0083] In some aspects, the present invention provides compositions of any one or more of aspects 1-6, wherein the API comprises lixenatide (Aspect 11).

[0084] In some aspects, the present invention provides compositions of any one or more of aspects 1-6, wherein the API comprises dulaglutide (Aspect 12).

[0085] In some aspects, the present invention provides compositions of any one or more of aspects 1-6, wherein the API comprises liraglutide (Aspect 13).

[0086] In some aspects, the present invention provides compositions of any one or more of aspects 1-6, wherein the API comprises abiglutide (Aspect 14).

[0087] In some aspects, the present invention provides compositions of any one or more of aspects 1-6, wherein the API is selected from the group comprising retaglutide, telposide, sminoside and peptidoside, and combinations thereof. (Aspect 15)

[0088] In some aspects, the present invention provides compositions of any one or more of aspects 1-6, wherein the API is selected from the group comprising lixisenatide, dulaglutide, liraglutide, abiglutide, retaglutide, pivostide, and telposide, and combinations thereof. (Aspect 16)

[0089] In some aspects, the present invention provides compositions of any one or more of aspects 1-16, wherein the API of the composition is present in an amount of about 1 wt.% to about 40 wt.% of the particles (Aspect 17).

[0090] In some aspects, the present invention provides compositions of any one or more of aspects 1-16, wherein the API of the composition is present in an amount of about 4 wt.% to about 40 wt.% of the particles (Aspect 18).

[0091] In some aspects, the present invention provides compositions of any one or more of aspects 1-16, wherein the API of the composition is present in an amount of about 10 wt.% to about 25 wt.% of the particles (Aspect 19).

[0092] In some aspects, the present invention provides compositions of any one or more of aspects 1-16, wherein the API of the composition is present in an amount of about 4 wt.% to about 15 wt.% of the particles (Aspect 20).

[0093] In some aspects, the present invention provides compositions of any one or more of aspects 1-20, wherein the composition is provided as a suspension formulation, and wherein the API is present in the suspension formulation in an amount of about 0.1 wt.% to about 10 wt.% of the suspension. (Aspect 21).

[0094] In some aspects, the present invention provides a composition of aspect 21, wherein the API is present in the suspension formulation in an amount of about 0.1 wt.% to about 3 wt.% of the suspension. (Aspect 22).

[0095] In some aspects, the present invention provides a composition of aspect 21, wherein the API is present in the suspension formulation in an amount of about 3 wt.% to about 10 wt.% of the suspension. (Aspect 23).

[0096] In some aspects, the present invention provides compositions of any one or more of aspects 1-23, wherein each dose of the composition provides about 1 mg to about 300 mg of a single API or an amount of the API component. (Aspect 24).

[0097] In some aspects, the present invention provides compositions of any one or more of aspects 1-24, wherein at least one of one or more biodegradable polymers of the carrier component comprises PLGA (Aspect 25).

[0098] In some aspects, the present invention provides compositions of any one or more of aspects 1-25, wherein at least one of one or more biodegradable polymers of the carrier component comprises PLA. (Aspect 26)

[0099] In some aspects, the present invention provides the composition of aspect 25, wherein the only biodegradable polymer of the carrier component is PLGA (aspect 27).

[0100] In some aspects, the present invention provides the composition of aspect 26, wherein the only biodegradable polymer of the carrier component is PLA (aspect 28).

[0101] In some aspects, the present invention provides compositions of any one or both of aspects 25 and 27, wherein the monomer ratio of lactic acid to glycolic acid (lactic acid: glycolic acid) is about 70-85: about 15-30 (Aspect 29).

[0102] In some aspects, the present invention provides compositions of any one or both of aspects 22 and 27, wherein the monomer ratio of lactic acid to glycolic acid (lactic acid: glycolic acid) is about 70-80: about 20-30 (Aspect 30).

[0103] In some aspects, the present invention provides compositions of any one or both of aspects 25 and 27, wherein the monomer ratio of lactic acid to glycolic acid (lactic acid:glycolic acid) is about 60-80 to about 20-40. (Aspect 31).

[0104] In some aspects, the invention provides compositions of any one or both of aspects 25 and 27, wherein the monomer ratio of lactic acid to glycolic acid (lactic acid: glycolic acid) is about 50: about 50 (Aspect 32).

[0105] In some aspects, the invention provides compositions of any one or both of aspects 25 and 27, wherein the monomer ratio of lactic acid to glycolic acid (lactic acid: glycolic acid) is about 75: about 25 (Aspect 33).

[0106] In some aspects, the invention provides compositions of any one or more of aspects 1-33, wherein the composition is provided as a lyophilized powder prepared for reconstitution prior to administration (Aspect 34).

[0107] In some aspects, the present invention provides compositions of any one or more of aspects 1-33, wherein the composition is provided as an injectable gel (Aspect 35).

[0108] In some aspects, the present invention provides compositions of any one or more of aspects 1-33, wherein the composition is provided as a suspension having a suspension density of particles between about 1% and about 50%, and wherein the API component is present in the suspension in an amount of about 0.4 mg / mL to about 120 mg / mL (Aspect 36).

[0109] In some aspects, the present invention provides compositions of any one or more of aspects 1-33, wherein the composition is provided as a suspension, and wherein the suspension further comprises one or more of a surfactant component, a suspension component, an osmotic pressure component, a buffer component, and a vehicle component (Aspect 37).

[0110] In some aspects, the present invention provides the composition of aspect 37, wherein the suspension comprises a surfactant component. (Aspect 38)

[0111] In some aspects, the invention provides compositions of any one or both of aspects 37 and 38, wherein the suspension comprises a surfactant component present in the suspension in an amount of about 0.01 wt.% to about 10 wt.% of the suspension (Aspect 39).

[0112] In some aspects, the invention provides compositions of any one or both of aspects 37 and 38, wherein the suspension comprises a surfactant component present in the suspension in an amount of about 0.05 wt.% to about 10 wt.% of the suspension (Aspect 40).

[0113] In some aspects, the present invention provides compositions of any one or more of aspects 37-40, wherein the suspension comprises a surfactant component present in the suspension in an amount of about 0.1 wt.% to about 5 wt.% of the suspension (Aspect 41).

[0114] In some aspects, the present invention provides compositions of any one or more of aspects 37-40, wherein the suspension comprises a surfactant component present in the suspension in an amount of about 0.1 wt.% to about 1 wt.% of the suspension (Aspect 42).

[0115] In some aspects, the present invention provides compositions of any one or more of aspects 37-42, wherein the suspension comprises a surfactant component present in the suspension in an amount of about 0.01 wt.% to about 0.10 wt.% of the suspension (Aspect 43).

[0116] In some aspects, the present invention provides compositions of any one or more of aspects 37-43, wherein the suspension comprises a surfactant component comprising polysorbate 20, polysorbate 80, polyvinyl alcohol, or any or all of the above combinations (Aspect 44).

[0117] In some aspects, the present invention provides compositions of any one or more of aspects 37-44, wherein the suspension comprises a suspension component (Aspect 45).

[0118] In some aspects, the present invention provides compositions of any one or more of aspects 37-45, wherein the suspension comprises a suspension component present in the suspension in an amount of about 0.05 wt.% to about 15 wt.% of the suspension (Aspect 46).

[0119] In some aspects, the present invention provides compositions of any one or more of aspects 37-46, wherein the suspension comprises a suspension component present in the suspension in an amount of about 0.1 wt.% to about 10 wt.% of the suspension (Aspect 47).

[0120] In some aspects, the present invention provides compositions of any one or more of aspects 37-47, wherein the suspension comprises a suspension component present in the suspension in an amount of about 1 wt.% to about 15 wt.% of the suspension (Aspect 48).

[0121] In some aspects, the present invention provides compositions of any one or more of aspects 37-48, wherein the suspension comprises a suspension component, polyethylene glycol, which is present in the suspension in an amount of about 0.1 wt.% to about 15 wt.% of the suspension (Aspect 49).

[0122] In some aspects, the present invention provides compositions of any one or more of aspects 37-49, wherein the mixture comprises a suspension component present in the suspension in an amount of about 5 wt.% to about 15 wt.% of the suspension (Aspect 50).

[0123] In some aspects, the present invention provides compositions of any one or more of aspects 37-50, wherein the suspension comprises a suspension component present in the suspension in an amount of about 0.1 wt.% to about 1 wt.% of the suspension (Aspect 51).

[0124] In some aspects, the present invention provides compositions of any one or more of aspects 37-51, wherein the suspension comprises a suspension component comprising polyethylene glycol, carboxymethyl cellulose, or a combination thereof (Aspect 52).

[0125] In some aspects, the present invention provides compositions of any one or more of aspects 37-52, wherein the suspension comprises one or more tension / osmotic pressure components. (Aspect 53)

[0126] In some aspects, the present invention provides compositions of any one or more of aspects 37-53, wherein the suspension comprises one or more tension / osmotic pressure components present in the suspension in an amount of about 0.005 wt.% to about 10 wt.% of the suspension (Aspect 54).

[0127] In some aspects, the present invention provides compositions of any one or more of aspects 37-54, wherein the suspension comprises a tonic / osmotic component sodium chloride, the sodium chloride being present in the suspension in an amount of about 0.1 wt.% to about 1.0 wt.% of the suspension (Aspect 55).

[0128] In some aspects, the present invention provides compositions of any one or more of aspects 37-55, wherein the suspension comprises a tension / osmotic pressure component, potassium chloride, which is present in the suspension in an amount of about 0.005 wt.% to about 0.015 wt.% of the suspension (Aspect 56).

[0129] In some aspects, the present invention provides compositions of any one or more of aspects 37-56, wherein the suspension comprises tension / osmotic pressure components sodium chloride and potassium chloride, the components being present in the suspension in an amount of about 0.005 wt.% to about 1.0 wt.% of the suspension (Aspect 57).

[0130] In some aspects, the present invention provides compositions of any one or more of aspects 37-57, wherein the suspension comprises one or more tension / osmotic pressure components present in the suspension in an amount of about 0.05 wt.% to about 10 wt.% of the suspension (Aspect 58).

[0131] In some aspects, the present invention provides compositions of any one or more of aspects 37-58, wherein the suspension comprises one or more tension / osmotic pressure components present in the suspension in an amount of about 0.1 wt.% to about 10 wt.% of the suspension (Aspect 59).

[0132] In some aspects, the present invention provides compositions of any one or more of aspects 37-59, wherein the suspension comprises a tension / osmotic pressure component present in the suspension in an amount of about 0.1 wt.% to about 1.0 wt.% of the suspension (Aspect 60).

[0133] In some aspects, the present invention provides compositions of any one or more of aspects 37-60, wherein the suspension comprises one or more tension / osmotic pressure components present in the suspension in an amount of about 0.1 wt.% to about 5 wt.% of the suspension (Aspect 61).

[0134] In some aspects, the present invention provides compositions of any one or more of aspects 37-61, wherein the suspension comprises one or more tension / osmotic pressure components present in the suspension in an amount of about 0.1 wt.% to about 1 wt.% of the suspension (Aspect 62).

[0135] In some aspects, the present invention provides compositions of any one or more of aspects 37-62, wherein the suspension comprises a tension / osmotic pressure component present in the suspension in an amount of about 0.005 wt.% to about 0.015 wt.% of the suspension (Aspect 63).

[0136] In some aspects, the invention provides compositions of any one or more of aspects 37-63, wherein the suspension comprises a tension / osmotic pressure component comprising sodium chloride, potassium chloride, mannitol, or a combination thereof. (Aspect 64)

[0137] In some aspects, the present invention provides compositions of any one or more of aspects 37-64, wherein the suspension comprises a buffering component (Aspect 65).

[0138] In some aspects, the present invention provides compositions of any one or more of aspects 37-65, wherein the suspension comprises a buffering component present in the suspension in an amount of about 0.005 wt.% to about 10 wt.% of the suspension (Aspect 66).

[0139] In some aspects, the present invention provides compositions of any one or more of aspects 37-66, wherein the suspension comprises a buffering component present in the suspension in an amount of about 0.01 wt.% to about 10 wt.% of the suspension (Aspect 67).

[0140] In some aspects, the present invention provides compositions of any one or more of aspects 37-67, wherein the suspension comprises a buffering component present in the suspension in an amount of about 0.05 wt.% to about 5 wt.% of the suspension (Aspect 68).

[0141] In some aspects, the present invention provides compositions of any one or more of aspects 37-68, wherein the suspension comprises one or more tension / osmotic pressure components present in the suspension in an amount of about 0.1 wt.% to about 1 wt.% of the suspension (Aspect 69).

[0142] In some aspects, the present invention provides compositions of any one or more of aspects 37-69, wherein the suspension comprises a tension / osmotic pressure component present in the suspension in an amount of about 0.005 wt.% to about 0.015 wt.% of the suspension (Aspect 70).

[0143] In some aspects, the present invention provides compositions of any one or more of aspects 37-70, wherein the suspension comprises a buffer component comprising sodium dihydrogen phosphate monohydrate and citric acid or disodium hydrogen phosphate and sodium hydroxide (Aspect 71).

[0144] In some aspects, the present invention provides compositions of any one or more of aspects 37-71, wherein the suspension comprises a buffer component comprising dipotassium hydrogen phosphate and disodium hydrogen phosphate (Aspect 72).

[0145] In some aspects, the present invention provides compositions of any one or more of aspects 37-72, wherein the suspension comprises a solvent component (Aspect 73).

[0146] In some aspects, the present invention provides compositions of any one or more of aspects 37-73, wherein the suspension comprises a solvent component present in the suspension in an amount of about 15 wt.% to about 99 wt.% of the suspension (Aspect 74).

[0147] In some aspects, the present invention provides compositions of any one or more of aspects 37-74, wherein the suspension comprises a solvent component present in the suspension in an amount of about 35 wt.% to about 99 wt.% of the suspension (Aspect 75).

[0148] In some aspects, the present invention provides compositions of any one or more of aspects 37-75, wherein the suspension comprises a solvent component present in the suspension in an amount of about 60 wt.% to about 80 wt.% of the suspension (Aspect 76).

[0149] In some aspects, the present invention provides compositions of any one or more of aspects 37-76, wherein the suspension comprises a solvent component comprising water for injection (WFI). (Aspect 77).

[0150] In some aspects, the present invention provides compositions of any one or more of aspects 1-77, wherein the telpoeptide API of the composition is present in an amount of about 1 wt.% to about 40 wt.% of the microparticles (Aspect 78).

[0151] In some aspects, the present invention provides compositions of any one or more of aspects 1-78, wherein the telpoeptide API of the composition is present in an amount of about 4 wt.% to about 40 wt.% of the microparticles (Aspect 79).

[0152] In some aspects, the present invention provides compositions of any one or more of aspects 1-79, wherein the telpoeptide API of the composition is present in an amount of about 10 wt.% to about 25 wt.% of the microparticles (Aspect 80).

[0153] In some aspects, the present invention provides compositions of any one or more of aspects 1-80, wherein the telpoeptide API of the composition is present in an amount of about 4 wt.% to about 15 wt.% of the microparticles (Aspect 81).

[0154] In some aspects, the present invention provides compositions of any one or more of aspects 1-81, wherein the composition is provided as a suspension formulation, and wherein the telposide API is present in the suspension formulation in an amount of about 0.1 wt.% to about 10 wt.% of the suspension. (Aspect 82).

[0155] In some aspects, the present invention provides a composition of aspect 82, wherein the telposide API is present in the suspension formulation in an amount of about 0.1 wt.% to about 3 wt.% of the suspension. (Aspect 83).

[0156] In some aspects, the present invention provides the composition of aspect 82, wherein the telposide API is present in the suspension formulation in an amount of about 3 wt.% to about 10 wt.% of the suspension. (Aspect 84).

[0157] In some aspects, the present invention provides compositions of any one or more of aspects 1-84, wherein less than about 20% of the administered dose of API is released within the first 24 hours after administration or placement in phosphate buffer at pH 7.4; less than about 80% of the administered dose of API is released within the first 14 days after administration or placement in phosphate buffer at pH 7.4; less than about 80% of the administered dose of API is released within the first 28 days after administration or placement in phosphate buffer at pH 7.4; or any or all of these combinations (Aspect 85).

[0158] In some aspects, the present invention provides compositions of any one or more of aspects 1-85, wherein less than about 20% of the administered dose of API is released within the first 24 hours after administration or after exposure to HEPES (N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid) at pH 7.3-7.5, preferably 7.4; less than about 80% of the administered dose of API is released within the first 14 days after administration or after exposure to HEPES at pH 7.3-7.5, preferably 7.4; less than about 80% of the administered dose of API is released within the first 28 days after administration or after exposure to HEPES at pH 7.3-7.5, preferably 7.4; or any or all of these combinations (Aspect 86).

[0159] In some aspects, the present invention provides compositions of any one or more of aspects 1-86, wherein less than about 2% of the administered dose of telpolide is released within the first 24 hours after administration or after being placed in 50 Mm pH 7.4 phosphate buffer + 13.7 mM NaCl + 0.05 % w / v BRIJ35 at a temperature of 37°C; and the initial cumulative release is <= 15%. (Aspect 87).

[0160] In some aspects, the present invention provides compositions of any one or more of aspects 1-86, wherein less than about 3% of the administered dose of telpolide is released within the first 24 hours after administration or after placement in phosphate buffer at pH 7 + 0.05% Brij35 at elevated temperature (45°C); less than about 7% of the administered dose of telpolide is released within the first 14 days after administration or after placement in phosphate buffer at pH 7 + 0.05% Brij35 at elevated temperature (45°C); less than about 38% of the administered dose of telpolide is released within the first 30 days after administration or after placement in phosphate buffer at pH 7 + 0.05% Brij35 at elevated temperature (45°C); less than about 82% of the administered dose of telpolide is released within the first 43 days after administration or after placement in phosphate buffer at pH 7 + 0.05% Brij35 at elevated temperature (45°C); or any or all of these combinations. (Aspect 88)

[0161] In some aspects, the present invention provides compositions of any one or more of aspects 1-86, wherein less than about 7% of the administered dose of telpolide is released within the first 24 hours after administration or after placement in 50 mM borate buffer + 0.05% Brij35 at elevated temperature (45°C); less than about 65% of the administered dose of telpolide is released within the first 14 days after administration or after placement in 50 mM borate buffer + 0.05% Brij35 at elevated temperature (45°C); less than about 80% of the administered dose of telpolide is released within the first 30 days after administration or after placement in 50 mM borate buffer + 0.05% Brij35 at elevated temperature (45°C); and less than about 80% of the administered dose of telpolide is released within the first 30 days after administration or after placement in 50 mM borate buffer + 0.05% Brij35 at elevated temperature (45°C). Released within the first 43 days after Brij35; or any or all of these combinations. (Aspect 89).

[0162] In some aspects, the present invention provides compositions of any one or more of aspects 1-89, wherein the microparticle releases an API at a rate that is at least substantially controlled, at least substantially controlled, at least essentially controlled, or controlled under physiological conditions, such that the release profile of the composition does not exhibit a detectable or significant burst release effect (Aspect 90).

[0163] In some aspects, the present invention provides compositions of any one or more of aspects 1-90, from which telpolide is released in a controlled release series selected from zero-order, primary, secondary, and tertiary release series and any pseudo-series thereof. Each possibility represents a separate implementation. (Aspect 91) preparation

[0164] In one aspect, the present invention provides a pharmaceutically acceptable controlled-release formulation comprising (1) a composition comprising a microparticle population, the microparticles of the composition comprising (a) one or more active pharmaceutical ingredients or pharmaceutically acceptable salts thereof, which are agonists of one or more of melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4) and melanocortin-5 (MC5) receptors, or agonists of one or more of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and glucagon receptors, or combinations thereof; (b) a carrier component comprising one or more biodegradable polymers; and (2) a solvent component. (Aspect 92).

[0165] In some aspects, the present invention provides a formulation of aspect 92, wherein the formulation is suitable for parenteral administration. (Aspect 93).

[0166] In some aspects, the present invention provides a formulation of aspect 93, wherein the formulation is administered by subcutaneous injection. (Aspect 94)

[0167] In some aspects, the present invention provides formulations of any one or more of aspects 92-94, wherein the API component of the formulation comprises retaglutide (aspect 95).

[0168] In some aspects, the present invention provides formulations of any one or more of aspects 92-94, wherein the API component of the formulation comprises telpolide (aspect 96).

[0169] In some aspects, the present invention provides formulations of any one or more of aspects 92-94, wherein the API component of the formulation comprises semanotide (Aspect 97).

[0170] In some aspects, the present invention provides formulations of any one or more of aspects 92-94, wherein the API component of the formulation comprises pevitin (Aspect 98).

[0171] In some aspects, the present invention provides formulations of any one or more of aspects 92-94, wherein the API component of the formulation comprises liximab (aspect 99).

[0172] In some aspects, the present invention provides formulations of any one or more of aspects 92-94, wherein the API component of the formulation comprises dulaglutide (Aspect 100).

[0173] In some aspects, the present invention provides formulations of any one or more of aspects 92-94, wherein the API component of the formulation comprises liraglutide (Aspect 101).

[0174] In some aspects, the present invention provides formulations of any one or more of aspects 92-94, wherein the API component of the formulation comprises abiglutide (Aspect 102).

[0175] In some aspects, the present invention provides formulations of any one or more of aspects 92-94, wherein the API component of the formulation is selected from the group comprising retaglutide, telposide, sminoside, and pivetide, and combinations thereof. (Aspect 103)

[0176] In some aspects, the present invention provides formulations of any one or more of aspects 92-94, wherein the API component of the formulation is selected from the group comprising retaglutide, pervitide, telposide, sminoside, lixisenatide, dulaglutide, liraglutide, and abiglutide, and combinations thereof. (Aspect 104)

[0177] In some aspects, the present invention provides formulations of any one or more of aspects 92-104, wherein the API component of the microparticles is present in an amount of about 1 wt.% to about 40 wt.% of the microparticles (Aspect 105).

[0178] In some aspects, the present invention provides a formulation of aspect 105, wherein the API component of the composition is present in an amount of about 4 wt.% to about 40 wt.% of the microparticles. (Aspect 106).

[0179] In some aspects, the present invention provides a formulation of aspect 105, wherein the API component of the formulation is present in an amount of about 4 wt.% to about 15 wt.% of the microparticles (aspect 107).

[0180] In some aspects, the present invention provides formulations of aspects 92-107, wherein the telpolide component is present in an amount of about 10 wt.% to about 25 wt.% of the microparticles (Aspect 108).

[0181] In some aspects, the present invention provides formulations of aspects 92-108, wherein the polymer component is present in an amount of about 75 wt.% to about 90 wt.% of the microparticles (Aspect 109).

[0182] In some aspects, the present invention provides formulations of aspects 92-109, wherein the telpolide component is present in an amount of about 10 wt.% to about 25 wt.% of the microparticles; and the polymer component is present in an amount of about 75 wt.% to about 90 wt.% of the microparticles (Aspect 110).

[0183] In some aspects, the present invention provides formulations of any one or more of aspects 92-110, wherein the formulation is provided as a suspension, and wherein the API component is present in the suspension in an amount of about 0.1 wt.% to about 10 wt.% of the suspension (Aspect 111).

[0184] In some aspects, the present invention provides a formulation of aspect 111, wherein the API component is present in the suspension in an amount of about 0.1 wt.% to about 3 wt.% of the suspension. (Aspect 112).

[0185] In some aspects, the present invention provides a formulation of aspect 111, wherein the API component is present in the suspension in an amount of about 3 wt.% to about 10 wt.% of the suspension. (Aspect 113).

[0186] In some aspects, the present invention provides formulations of aspects 92-113, wherein the polymer component is present in an amount of about 1 wt.% to about 45 wt.% of the suspension (aspect 114).

[0187] In some aspects, the present invention provides formulations of aspects 112-114, wherein the telpoeptide component is present in an amount of about 3 wt.% to about 10 wt.%, and the polymer component is present in an amount of about 15 wt.% to about 35 wt.% of the droplet (Aspect 115).

[0188] In some aspects, the present invention provides formulations of any one or more of aspects 92-115, wherein each dose of the formulation provides an amount of about 1 mg to about 300 mg of a single API or a component of the API. (Aspect 116).

[0189] In some aspects, the present invention provides formulations of any one or more of aspects 92-116, wherein at least one of one or more biodegradable polymers of the carrier component comprises PLGA (Aspect 117).

[0190] In some aspects, the present invention provides formulations of any one or more of aspects 92-117, wherein at least one of one or more biodegradable polymers of the carrier component comprises PLA (Aspect 118).

[0191] In some aspects, the present invention provides a formulation of aspect 117, wherein the only biodegradable polymer of the carrier component is PLGA (aspect 119).

[0192] In some aspects, the present invention provides a formulation of aspect 118, wherein the only biodegradable polymer of the carrier component is PLA (aspect 120).

[0193] In some aspects, the present invention provides formulations of any one or both of aspects 117 and 119, wherein the monomer ratio of lactic acid to glycolic acid (lactic acid: glycolic acid) is about 70-85: about 15-30. (Aspect 121).

[0194] In some aspects, the present invention provides formulations of any one or both of aspects 118 and 120, wherein the monomer ratio of lactic acid to glycolic acid (lactic acid: glycolic acid) is about 75: about 25 (aspect 122).

[0195] In some aspects, the present invention provides formulations of any one or both of aspects 118 and 120, wherein the monomer ratio of lactic acid to glycolic acid (lactic acid: glycolic acid) is about 50: about 50 (aspect 123).

[0196] In some aspects, the present invention provides compositions of any one or more of aspects 92-123, wherein the active pharmaceutical ingredient is encapsulated in biodegradable sustained-release microparticles, wherein the microparticles are in the form of free-flowing powder having an angle of repose of less than about 45 degrees (Aspect 124).

[0197] In some aspects, the present invention provides compositions of any one or more of aspects 92-123, wherein the active pharmaceutical ingredient is encapsulated in biodegradable sustained-release microparticles, wherein the microparticles are in the form of free-flowing powder having an angle of repose of less than about 40 degrees (Aspect 125).

[0198] In some aspects, the present invention provides compositions of any one or more of aspects 92-123, wherein the active pharmaceutical ingredient is encapsulated in biodegradable sustained-release microparticles, wherein the microparticles are in the form of free-flowing powder having an angle of repose of less than about 35 degrees (Aspect 126).

[0199] In some aspects, the present invention provides formulations of any one or more of aspects 92-107 and 78-84, wherein the formulation is provided as a separate combination of a lyophilized particulate composition and a diluent, wherein the diluent is used to reconstitute the lyophilized particulate composition prior to administration (Aspect 127).

[0200] In some aspects, the present invention provides formulations of any one or more of aspects 92-127, wherein the formulation is provided as a ready-to-use suspension or an injectable gel (Aspect 128).

[0201] In some aspects, the present invention provides formulations of any one or more of aspects 92-128, wherein the composition is provided as a suspension having a suspension density of particles between about 1% and about 50%, and wherein the API component is present in the suspension in an amount of about 0.4 mg / mL to about 120 mg / mL (Aspect 129).

[0202] In some aspects, the present invention provides formulations of any one or more of aspects 92-129, wherein the composition is provided as a suspension, and wherein the suspension further comprises one or more of a surfactant component, a suspension component, an osmotic pressure component, a buffer component, and a solvent component (Aspect 130).

[0203] In some aspects, the present invention provides a formulation of aspect 130, wherein the suspension comprises a surfactant component (aspect 131).

[0204] In some aspects, the present invention provides a composition of any one or both of aspects 130 and 131, wherein the suspension comprises a surfactant component present in the suspension in an amount of about 0.01 wt.% to about 10 wt.% of the suspension (Aspect 132).

[0205] In some aspects, the present invention provides formulations of any one or both of aspects 130 and 131, wherein the suspension comprises a surfactant component present in the suspension in an amount of about 0.05 wt.% to about 10 wt.% of the suspension (Aspect 133).

[0206] In some aspects, the present invention provides formulations of any one or more of aspects 130-133, wherein the suspension comprises a surfactant component present in the suspension in an amount of about 0.1 wt.% to about 5 wt.% of the suspension (Aspect 134).

[0207] In some aspects, the present invention provides formulations of any one or more of aspects 130-134, wherein the suspension comprises a surfactant component present in the suspension in an amount of about 0.1 wt.% to about 1 wt.% of the suspension (Aspect 135).

[0208] In some aspects, the present invention provides compositions of any one or more of aspects 130-135, wherein the suspension comprises a surfactant component present in the suspension in an amount of about 0.01 wt.% to about 0.10 wt.% of the suspension (Aspect 136).

[0209] In some aspects, the present invention provides formulations of any one or more of aspects 130-136, wherein the suspension comprises a surfactant component comprising polysorbate 20, polysorbate 80, polyvinyl alcohol, or any or all of the above combinations (Aspect 137).

[0210] In some aspects, the present invention provides formulations of any one or more of aspects 130-137, wherein the suspension comprises a suspension component (Aspect 138).

[0211] In some aspects, the present invention provides formulations of any one or more of aspects 130-138, wherein the suspension comprises a suspension component present in the suspension in an amount of about 0.05 wt.% to about 15 wt.% of the suspension (Aspect 139).

[0212] In some aspects, the present invention provides formulations of any one or more of aspects 130-139, wherein the suspension comprises a suspension component present in the suspension in an amount of about 0.1 wt.% to about 10 wt.% of the suspension (Aspect 140).

[0213] In some aspects, the present invention provides compositions of any one or more of aspects 130-140, wherein the suspension comprises a suspension component present in the suspension in an amount of about 1 wt.% to about 15 wt.% of the suspension (Aspect 141).

[0214] In some aspects, the present invention provides compositions of any one or more of aspects 130-141, wherein the suspension comprises a suspension component present in the suspension in an amount of about 5 wt.% to about 15 wt.% of the suspension (Aspect 142).

[0215] In some aspects, the present invention provides formulations of any one or more of aspects 130-142, wherein the suspension comprises a suspension component present in the suspension in an amount of about 0.1 wt.% to about 1 wt.% of the suspension (Aspect 143).

[0216] In some aspects, the present invention provides formulations of any one or more of aspects 130-143, wherein the suspension comprises a suspension component comprising polyethylene glycol, carboxymethyl cellulose, or a combination thereof (Aspect 144).

[0217] In some aspects, the present invention provides formulations of any one or more of aspects 130-144, wherein the suspension comprises one or more tonic / osmotic components (Aspect 145).

[0218] In some aspects, the present invention provides compositions of any one or more of aspects 130-145, wherein the suspension comprises one or more tension / osmotic pressure components present in the suspension in an amount of about 0.005 wt.% to about 10 wt.% of the suspension (Aspect 146).

[0219] In some aspects, the present invention provides formulations of any one or more of aspects 130-146, wherein the suspension comprises one or more tonic / osmotic components present in the suspension in an amount of about 0.1 wt.% to about 10 wt.% of the suspension (Aspect 147).

[0220] In some aspects, the present invention provides formulations of any one or more of aspects 130-147, wherein the suspension comprises one or more tonic / osmotic components present in the suspension in an amount of about 0.05 wt.% to about 10 wt.% of the suspension (Aspect 148).

[0221] In some aspects, the present invention provides formulations of any one or more of aspects 130-148, wherein the suspension comprises one or more tonic / osmotic components present in the suspension in an amount of about 0.1 wt.% to about 5 wt.% of the suspension (Aspect 149).

[0222] In some aspects, the present invention provides formulations of any one or more of aspects 130-149, wherein the suspension comprises a tonic / osmotic pressure component present in the suspension in an amount of about 0.1 wt.% to about 1 wt.% of the suspension (Aspect 150).

[0223] In some aspects, the present invention provides compositions of any one or more of aspects 130-150, wherein the suspension comprises a tension / osmotic pressure component present in the suspension in an amount of about 0.005 wt.% to about 0.015 wt.% of the suspension (Aspect 151).

[0224] In some aspects, the present invention provides formulations of any one or more of aspects 130-151, wherein the suspension comprises one or more tonic / osmotic components comprising sodium chloride, potassium chloride, mannitol, or combinations thereof (Aspect 152).

[0225] In some aspects, the present invention provides formulations of any one or more of aspects 130-152, wherein the suspension comprises a buffer component (Aspect 153).

[0226] In some aspects, the present invention provides compositions of any one or more of aspects 130-153, wherein the suspension comprises a buffering component present in the suspension in an amount of about 0.005 wt.% to about 10 wt.% of the suspension (Aspect 154).

[0227] In some aspects, the present invention provides formulations of any one or more of aspects 130-154, wherein the suspension comprises a buffer component present in the suspension in an amount of about 0.01 wt.% to about 10 wt.% of the suspension (Aspect 155).

[0228] In some aspects, the present invention provides formulations of any one or more of aspects 130-155, wherein the suspension comprises a buffer component present in the suspension in an amount of about 0.05 wt.% to about 5 wt.% of the suspension (Aspect 156).

[0229] In some aspects, the present invention provides formulations of any one or more of aspects 130-156, wherein the suspension comprises a tonic / osmotic pressure component present in the suspension in an amount of about 0.1 wt.% to about 1 wt.% of the suspension (Aspect 157).

[0230] In some aspects, the present invention provides formulations of any one or more of aspects 130-157, wherein the suspension comprises a buffer component comprising sodium dihydrogen phosphate monohydrate and citric acid or disodium hydrogen phosphate and sodium hydroxide and HEPES (Aspect 158).

[0231] In some aspects, the present invention provides compositions of any one or more of aspects 130-158, wherein the suspension comprises a buffer component comprising dipotassium hydrogen phosphate and disodium hydrogen phosphate (Aspect 159).

[0232] In some aspects, the present invention provides formulations of any one or more of aspects 130-159, wherein the suspension comprises a solvent component (Aspect 160).

[0233] In some aspects, the present invention provides compositions of any one or more of aspects 130-160, wherein the suspension comprises a solvent component present in the suspension in an amount of about 15 wt.% to about 99 wt.% of the suspension (Aspect 161).

[0234] In some aspects, the present invention provides formulations of any one or more of aspects 130-161, wherein the suspension comprises a solvent component present in the suspension in an amount of about 35 wt.% to about 99 wt.% of the suspension (Aspect 162).

[0235] In some aspects, the present invention provides formulations of any one or more of aspects 130-162, wherein the suspension comprises a solvent component present in the suspension in an amount of about 60 wt.% to about 80 wt.% of the suspension (Aspect 163).

[0236] In some aspects, the present invention provides formulations of any one or more of aspects 130-163, wherein the suspension comprises a solvent component comprising water for injection (WFI). (Aspect 164).

[0237] In some aspects, the present invention provides formulations of any one or more of aspects 130-164, wherein less than about 20% of the administered dose of API is released within the first 24 hours after administration or placement in phosphate buffer at pH 7.4; less than about 80% of the administered dose of API is released within the first 14 days after administration or placement in phosphate buffer at pH 7.4; less than about 80% of the administered dose of API is released within the first 28 days after administration or placement in phosphate buffer at pH 7.4; or any or all of these combinations (Aspect 165).

[0238] In some aspects, the present invention provides compositions of any one or more of aspects 1-86, wherein less than about 2% of the administered dose of telpolide is released within the first 24 hours after administration or after being placed in 50 mM pH 7.4 phosphate buffer + 13.7 mM NaCl + 0.05 % w / v BRIJ35 at a temperature of 37°C; and the initial cumulative release is <= 15% (Aspect 166).

[0239] In some aspects, the present invention provides formulations of any one or more of aspects 130-166, wherein less than about 3% of the administered dose of telpolide is released within the first 24 hours after administration or after placement in phosphate buffer at pH 7 + 0.05% Brij35 at elevated temperature (45°C); less than about 7% of the administered dose of telpolide is released within the first 14 days after administration or after placement in phosphate buffer at pH 7 + 0.05% Brij35 at elevated temperature (45°C); less than about 38% of the administered dose of telpolide is released within the first 30 days after administration or after placement in phosphate buffer at pH 7 + 0.05% Brij35 at elevated temperature (45°C); less than about 82% of the administered dose of telpolide is released within the first 43 days after administration or after placement in phosphate buffer at pH 7 + 0.05% Brij35 at elevated temperature (45°C); or any or all of these combinations. (Aspect 167).

[0240] In some aspects, the present invention provides formulations of any one or more of aspects 130-167, wherein less than about 7% of the administered dose of telpotetamide is released within the first 24 hours after administration or after placement in 50 mM borate buffer + 0.05% Brij35 at elevated temperature (45°C); less than about 65% of the administered dose of telpotetamide is released within the first 14 days after administration or after placement in 50 mM borate buffer + 0.05% Brij35 at elevated temperature (45°C); less than about 80% of the administered dose of telpotetamide is released within the first 30 days after administration or after placement in 50 mM borate buffer + 0.05% Brij35 at elevated temperature (45°C); and less than about 80% of the administered dose of telpotetamide is released within the first 30 days after administration or after placement in 50 mM borate buffer + 0.05% Brij35 at elevated temperature (45°C). Released within the first 43 days after Brij35; or any or all of these combinations. (Aspect 168).

[0241] In some aspects, the present invention provides formulations of any one or more of aspects 130-164, wherein less than about 20% of the administered dose of API is released within the first 24 hours after administration or placement in HEPES at pH 7.4; less than about 80% of the administered dose of API is released within the first 14 days after administration or placement in HEPES at pH 7.4; less than about 80% of the administered dose of API is released within the first 28 days after administration or placement in HEPES at pH 7.4; or any or all of these combinations (Aspect 169).

[0242] In some aspects, the present invention provides formulations of any one or more of aspects 130-169, wherein the particles of the formulation release the API at a rate that is at least substantially controlled, at least substantially controlled, at least essentially controlled, or controlled under physiological conditions, such that the release profile of the formulation does not exhibit a detectable or significant burst release effect (Aspect 170). Product preparation process

[0243] In one aspect, the present invention provides a pharmaceutically acceptable, controlled-release formulation prepared by a process comprising (1) establishing a microparticle population formed by a process comprising the steps of: (a) forming a biemulsion comprising (I) a first phase comprising (A) one or more active pharmaceutical ingredients (APIs) being agonists of one or more of melanocortin-1 receptor (MC1); melanocortin-2 receptor (MC2); melanocortin-3 receptor (MC3); melanocortin-4 receptor (MC4); and melanocortin-5 receptor (MC5), or incretin hormone agonists being glucagon-like peptide-1 (GLP-1) agonists; glucose-dependent insulinotropic peptide (GIP); and one or more agonists of glucagon receptors, or combinations thereof, and (B) a first solvent. The first phase comprises (a) an aqueous or polar solvent, wherein the first solvent optionally contains a surfactant component, a buffer component, or both, and wherein the first phase optionally contains an osmotic component; (ii) a second phase comprising a carrier component and a second solvent, the carrier component comprising one or more biodegradable polymers, wherein the second solvent is an organic solvent, and wherein the second phase optionally contains a surfactant; and (iii) a third phase comprising (a) a third solvent, wherein the third solvent is an aqueous or polar solvent, wherein the third solvent optionally contains a buffer component, a filler component, or both; and (b) a surfactant; (b) solvent extraction to remove the second organic solvent; and (c) concentrating the particles produced by steps (a) and (b) and collecting the particle population, wherein (i) the maximum size of the particle population in any direction is about 10. (i) between µm and about 120 µm; (ii) at least about 70% of the particles in the particle population have a maximum diameter in any direction that is within 10% of the average particle diameter in any direction of the particle population; and (iii) at least about 70% of the particles in the composition have a maximum size in any direction that is within 10% of the average size of the particles in any other one or more directions of the same particle population; (2) washing the particle population; and (3) combining the washed particle population with the solvent component. (Aspect 171).

[0244] In some aspects, the present invention provides a formulation of aspect 171, wherein the first phase does not contain a surfactant. (Aspect 172).

[0245] In some aspects, the present invention provides formulations of any one or both of aspects 171 and 172, wherein the second phase does not contain a surfactant. (Aspect 173).

[0246] In some aspects, the present invention provides formulations of any one or more of aspects 171-173, wherein the second phase does not contain a tonic / osmotic component (Aspect 174).

[0247] In some aspects, the present invention provides formulations of any one or more of aspects 171-174, wherein the formulation has any one or more characteristics of formulations of any one or more of aspects 92-170 (Aspect 175). Manufacturing method

[0248] In one aspect, the present invention provides a method for manufacturing a composition of pharmaceutically acceptable, controlled-release microparticles suitable for parenteral administration, the method comprising (1) establishing a microparticle population by: (a) forming a biemulsion comprising (I) a first phase comprising (A) one or more active pharmaceutical ingredients or pharmaceutically acceptable salts thereof, which are agonists of one or more of melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors, or glucagon-like peptide-1 (GLP-1); glucose-dependent insulinotropic peptide (GIP); and one or more agonists of glucagon receptors, or combinations thereof, and (B) a first solvent, wherein the first solvent is aqueous or The first phase comprises a polar solvent, wherein the first solvent optionally includes a surfactant component, a buffer component, or both, and wherein the first phase optionally includes an osmotic component; (II) a second phase comprising a carrier component and a second solvent, the carrier component comprising one or more biodegradable polymers, wherein the second solvent is an organic solvent, and wherein the second phase optionally includes a surfactant; and (III) a third phase comprising (A) a third solvent, wherein the third solvent is an aqueous or polar solvent, wherein the third solvent optionally includes a buffer component, a filler component, or both; and (B) a surfactant; (b) solvent extraction to remove the second organic solvent; and (c) concentrating the particles produced by steps (a) and (b) and collecting the particle population, wherein (I) the maximum size of the particle population in any direction is about 1. (i) between µm and about 120 µm; (ii) at least about 70% of the particles in the particle population have a maximum diameter in any direction that is within 10% of the average particle diameter in any direction of the particle population; and (iii) at least about 70% of the particles in the composition have a maximum size in any direction that is within 10% of the average size of the particles in any other one or more directions; (2) the particle population is thoroughly washed to remove at least 95% of any API in the composition that is not bound to the particles, not encapsulated by the particles, or otherwise not associated with the particles. (Aspect 176).

[0249] In some aspects, the present invention provides the method of aspect 176, wherein the first phase does not contain a surfactant. (Aspect 177)

[0250] In some aspects, the invention provides a method of either or both of aspects 176 and 177, wherein the second phase does not contain a surfactant (Aspect 178).

[0251] In some aspects, the present invention provides a method of any one or more of aspects 176-178, wherein the second phase does not contain a tension / osmotic pressure component (Aspect 179).

[0252] In some aspects, the present invention provides a method of any one or more of aspects 176-179, wherein the composition produced by the method has any one or more properties of the compositions of any one or more of aspects 1-76 (Aspect 180).

[0253] In some aspects, the present invention provides a method of any one or more of aspects 176-180, wherein the method further comprises the step of adding a solvent component to form a formulation suitable for immediate administration (Aspect 181).

[0254] In some aspects, the present invention provides a method of aspect 181, wherein the method produces an formulation having any one or more of the properties of any one or more of aspects 92-175 (Aspect 182). Treatment

[0255] In some aspects, the present invention provides a method for achieving detectable or significant weight loss in mammalian subjects, wherein the method comprises administering, during an effective period, parenterally: an effective amount of any one or more of the compositions of any one or more of aspects 1-91; an effective amount of any one or more of the formulations of any one or more of aspects 92-175; a composition prepared by any one or more of the manufacturing methods of aspects 176-180; or a formulation prepared by any one or both of aspects 181 and 182, and wherein the method comprises administering such compositions or formulations no more than once a month (Aspect 183).

[0256] In some aspects, the present invention provides a method for treating obesity in mammalian subjects, wherein the method comprises administering, during an effective period, parenterally: an effective amount of any one or more of the compositions of any one or more of aspects 1-91; an effective amount of any one or more of the formulations of any one or more of aspects 92-175; a composition prepared by any one or more of the manufacturing methods of aspects 176-180; or a formulation prepared by any one or both of aspects 181 and 182, and wherein the method comprises administering such compositions or formulations no more than once a month (Aspect 184).

[0257] In some aspects, the present invention provides a method for treating diabetes, such as type II diabetes, in mammalian subjects, wherein the method comprises administering, during an effective period, parenterally: an effective amount of any one or more of the compositions of any one or more of aspects 1-91; an effective amount of any one or more of the formulations of any one or more of aspects 92-175; a composition prepared by any one or more of the manufacturing methods of aspects 176-180; or a formulation prepared by any one or both of aspects 181 and 182, and wherein the method comprises administering such compositions or formulations no more than once a month (aspect 185).

[0258] In some aspects, the present invention provides a method for detectably or significantly reducing fasting blood glucose levels in mammalian subjects, wherein the method comprises administering, during an effective period, parenterally: an effective amount of any one or more of the compositions of any one or more of aspects 1-91; an effective amount of any one or more of the formulations of any one or more of aspects 92-175; a composition prepared by any one or more of the manufacturing methods of aspects 176-180; or a formulation prepared by any one or both of aspects 181 and 182, and wherein the method comprises administering such compositions or formulations no more than once a month (Aspect 186).

[0259] In some aspects, the present invention provides a method for detectably or significantly reducing hemoglobin A1c (HbA1c) levels in a mammalian subject, wherein the method comprises administering, during an effective period, parenterally: an effective amount of any one or more of the compositions of any one or more of aspects 1-91; an effective amount of any one or more of the formulations of any one or more of aspects 92-175; a composition prepared by any one or more of the manufacturing methods of aspects 176-180; or a formulation prepared by any one or both of aspects 181 and 182, and wherein the method comprises administering such compositions or formulations no more than once a month (Aspect 187).

[0260] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-187, wherein the method comprises administering the composition or formulation no more than once every two weeks (Aspect 188).

[0261] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-188, wherein the method comprises administering the composition or formulation no more than once every three weeks (Aspect 189).

[0262] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-189, wherein the method comprises administering the composition or formulation no more than once every about 4 weeks (Aspect 190).

[0263] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-190, wherein the method comprises administering the composition or formulation no more than once every six weeks (Aspect 191).

[0264] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-191, wherein the method comprises administering the composition or formulation no more than once every two months (Aspect 192).

[0265] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-192, wherein the method comprises administering the composition or formulation no more than once every three months (Aspect 193).

[0266] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-193, wherein the method comprises administering the composition or formulation no more than once every about 4 months (Aspect 194).

[0267] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-194, wherein the method comprises administering the composition or formulation no more than once every about 5 months (Aspect 195).

[0268] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-195, wherein the method comprises administering the composition or formulation no more than once every six months (Aspect 196).

[0269] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-196, wherein the method comprises administering the composition or formulation no more than once every about 7 months (Aspect 197).

[0270] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-197, wherein the method comprises administering the composition or formulation no more than once every about 8 months (Aspect 198).

[0271] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-198, wherein the method comprises administering the composition or formulation no more than once every nine months (Aspect 199).

[0272] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-199, wherein the method comprises administering the composition or formulation no more than once every about 10 months. (Aspect 200).

[0273] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-200, wherein the method comprises administering the composition or formulation no more than once every about 11 months. (Aspect 201).

[0274] In some aspects, the present invention provides one or more of the methods of any one or more of aspects 183-201, wherein the method comprises administering the composition or formulation no more than once every 12 months (Aspect 202).

[0275] In some aspects, the present invention provides one or more compositions, formulations, or methods provided in the section entitled “Further Exemplary Embodiments”, wherein, in addition, the compositions may further comprise any one or more properties provided in any one or more of aspects 1-91; the formulations may further comprise any one or more properties provided in any one or more of aspects 92-175; the compositions may be prepared according to any one or more methods described in any one or more of aspects 176-180; and the formulations may be prepared according to any one or more methods described in any one or both of aspects 181 and 182. (Aspect 203).

[0276] A method of treating obesity in a patient in need, comprising administering to the patient a long-acting parenteral pharmaceutical composition comprising one or more active pharmaceutical ingredients or pharmaceutically acceptable salts thereof and a carrier component, the one or more active pharmaceutical ingredients or pharmaceutically acceptable salts thereof having detectable or significant agonist activity against one or more of the following: melanocortin-1 receptor (MC1-R), melanocortin-2 receptor (MC2-R), melanocortin-3 receptor (MC3-R), melanocortin-4 receptor (MC4-R), melanocortin-5 receptor (MC5-R), glucagon-like peptide-1 (GLP-1) receptor; glucose-dependent insulinotropic peptide (GIP) receptor; glucagon receptor, wherein the carrier component comprises one or more biodegradable polymers, wherein the composition is administered from once every two weeks to once every six months. (Aspect 204).

[0277] In some aspects, the present invention provides compositions of any one or more of aspects 1-86, wherein the composition provides less than 2% of the administered dose of telpolide burst release within twenty-four hours after administration; and the initial cumulative release is <= 15% (Aspect 205).

[0278] In some aspects, the present invention provides compositions of any one or more of aspects 1-90, wherein the microparticles release API at 37°C and pH 7.4, wherein a plateau is expected at 80% release. After an observed hysteresis period of one month, stable release is observed to continue for approximately two to three months (Aspect 206).

[0279] In some aspects, the present invention provides compositions of any one or more of aspects 1-90, wherein the microparticles release API at 37°C and pH 7.4, wherein a plateau is expected to be reached at 80% release. After an observed hysteresis period of one month, stable release is observed to continue for approximately six months (Aspect 207).

[0280] In some aspects, the present invention provides compositions of any one or more of aspects 92-123, wherein the active pharmaceutical ingredient is encapsulated in biodegradable sustained-release microparticles, wherein an encapsulation efficiency of at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% is obtained. (Aspect 208) Composition / Formulation

[0281] In some aspects, the present invention provides compositions of any one or more of aspects 92-123, wherein the active pharmaceutical ingredient is encapsulated in biodegradable sustained-release microparticles, wherein an encapsulation efficiency of greater than 60%, greater than 65%, greater than 70%, greater than 75%, greater than 80%, greater than 85%, greater than 90%, or greater than 95% is obtained. (Aspect 209)

[0282] In some aspects, the present invention provides compositions of any one or more of aspects 92-123, wherein the active pharmaceutical ingredient is encapsulated in biodegradable sustained-release microparticles, wherein an encapsulation efficiency of at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% is obtained. (Aspect 210)

[0283] In some aspects, the present invention provides compositions of any one or more of aspects 1-85, wherein less than about 20% of the administered dose of API is released within the first 24 hours after administration or after incubation in 50 mM pH 7.4 phosphate buffer + 13.7 mM NaCl + 0.05% w / v BRIJ35; less than about 80% of the administered dose of API is released within the first 14 days after administration or after incubation in 50 mM pH 7.4 phosphate buffer + 13.7 mM NaCl + 0.05% w / v BRIJ35; less than about 80% of the administered dose of API is released within the first 28 days after administration or after incubation in 50 mM pH 7.4 phosphate buffer + 13.7 mM NaCl + 0.05% w / v BRIJ35, or any or all of these combinations (Aspect 211).

[0284] In some aspects, the present invention provides formulations of any one or more of aspects 130-164, wherein less than about 20% of the administered dose of API is released within the first 24 hours after administration or after placement in phosphate buffer at pH 7 + 0.05% Brij35; less than about 80% of the administered dose of API is released within the first 14 days after administration or after placement in phosphate buffer at pH 7 + 0.05% Brij35; less than about 80% of the administered dose of API is released within the first 28 days after administration or after placement in phosphate buffer at pH 7 + 0.05% Brij35; or any or all of these combinations. (Aspect 212) Other exemplary embodiments

[0285] One aspect of the present invention provides a method for preparing an agent for treating obesity, diabetes (e.g., type II diabetes), or both, wherein an aqueous first phase comprising about 0.1 wt.% to about 20 wt.% of a water-soluble glucagon-like peptide-1 (GLP-1) agonist and / or a glucagon receptor agonist and / or a glucose-dependent insulinotropic peptide (GIP) agonist and / or melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) receptor agonist is prepared, and a second phase comprising about 5 wt.% to about 50 wt.% of a biodegradable polymer and an organic solvent is prepared. The first phase is introduced into the second phase via a membrane to form a primary (w / o) emulsion comprising at least substantially (e.g., at least essentially) monodisperse microdroplets of the first phase in the second phase. The primary (w / o) emulsion is dispersed in a third aqueous phase to form a bi (w / o / w) emulsion comprising microdroplets of the primary (w / o) emulsion in the third phase. More than 70% of the microdroplets are substantially equal in size, with deviations from the average size within about 10%. After solvent removal, a composition of highly monodisperse microparticles of the GLP-1 agonist and / or glucagon receptor agonist and / or GIP agonist and / or melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) receptor agonists in a biodegradable matrix of the biodegradable polymer is obtained. This microparticle formulation can be prepared in a pharmaceutically acceptable form for subcutaneous administration.

[0286] One aspect of the present invention provides a method for preparing an agent for treating obesity, diabetes (e.g., type II diabetes), or both, wherein an aqueous first phase comprising about 0.1 wt.% to about 20 wt.% of a water-soluble glucagon-like peptide-1 (GLP-1) agonist and / or a glucagon receptor agonist and / or a glucose-dependent insulinotropic peptide (GIP) agonist and / or melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) receptor agonist is prepared, and a second phase comprising about 5 wt.% to about 50 wt.% of a biodegradable polymer and an organic solvent is prepared. The first phase is introduced into the second phase via a membrane to form a primary (w / o) emulsion comprising at least substantially (e.g., at least essentially) monodisperse microdroplets of the first phase in the second phase. The primary (w / o) emulsion is dispersed in a third aqueous phase to form a bi (w / o / w) emulsion comprising microdroplets of the primary (w / o) emulsion in the third phase. More than 80% of the microdroplets are substantially equal in size, with deviations from the average size within about 10%. After solvent removal, a composition of highly monodisperse microparticles of the GLP-1 agonist and / or glucagon receptor agonist and / or GIP agonist and / or melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) receptor agonists in a biodegradable matrix of the biodegradable polymer is obtained. This microparticle formulation can be prepared in a pharmaceutically acceptable form for subcutaneous administration.

[0287] One aspect of the present invention provides a long-acting parenteral pharmaceutical composition comprising a stable formulation of telpolide, wherein telpolide is present in the range of about 0.1 wt.% to about 10 wt.% based on the total weight of the suspension (about 1 wt.% to about 40 wt.% based on the total weight of the microparticles / microspheres). Another aspect of the present invention provides a long-acting parenteral pharmaceutical composition comprising a stable formulation of telpolide, wherein telpolide is present in the range of about 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microparticles / microspheres).

[0288] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 0.1 wt.% to about 3 wt.% based on the total weight of the suspension (about 1 wt.% to about 10 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. In some aspects, this composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In still other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In still other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0289] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in an amount ranging from 3 wt.% to about 10 wt.% based on the total weight of the suspension (approximately 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. Based on the total weight of the suspension, the solvent is present in an amount ranging from about 60 wt.% to about 80 wt.%.

[0290] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. In some aspects, this composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In still other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In still other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0291] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. In some aspects, this composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In still other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In still other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 80. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0292] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. In some aspects, this composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In still other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In still other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 80. The surfactant is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0293] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. In some aspects, this composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In still other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In still other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polyvinyl alcohol. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0294] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. In some aspects, this composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In still other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In still other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polyvinyl alcohol. The surfactant is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0295] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. In some aspects, this composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In still other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In still other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is carboxymethyl cellulose. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0296] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. In some aspects, this composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In still other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In still other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is carboxymethyl cellulose. The suspending agent is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0297] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. In some aspects, this composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In still other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In still other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 1 wt.% to about 10 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0298] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In some other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0299] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In some other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is mannitol. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0300] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In some other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is mannitol. The osmotic pressure regulator is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0301] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In some other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0302] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In some other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is disodium hydrogen phosphate and sodium hydroxide. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0303] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In some other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is disodium hydrogen phosphate and sodium hydroxide. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0304] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some other embodiments, the composition ratio is a lactate:glycolic acid ratio of 75:25. In some other embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is disodium hydrogen phosphate and sodium hydroxide. The buffer is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0305] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 75:25. In another embodiment, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is pure water. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0306] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 10 wt.% to about 25 wt.% based on the total weight of the microspheres. Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 12 wt.% to about 21 wt.% based on the total weight of the microspheres. The biodegradable polymer according to this embodiment is poly(D,L-lactide-co-glycolic acid) (PLGA). The amount of PLGA is in the range of about 75 wt.% to about 90 wt.% based on the total weight of the microspheres. The composition of PLGA is described based on the molar ratio of the monomers used. In another embodiment, in some aspects, the composition ratio is a 50:50 lactate:glycolic acid ratio. In another embodiment, in some aspects, the composition ratio is a 75:25 lactate:glycolic acid ratio. In another embodiment, the biodegradable polymer is poly(D,L-lactide) (PLA). In another embodiment, the amount of PLA is in the range of about 75 wt.% to about 90 wt.% based on the total weight of the microspheres. The surfactant according to this embodiment is polysorbate 20. In another embodiment, the surfactant is present in the range of about 0.01 wt.% to about 0.1 wt.% based on the total weight of the formulation. The suspending agent according to this embodiment is polyethylene glycol. In another embodiment, the suspending agent is present in the range of about 1 wt.% to about 15 wt.% based on the total weight of the suspension. In another embodiment, the suspending agent is present in the range of about 5 wt.% to about 15 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator according to this embodiment is potassium chloride. The osmotic pressure regulator according to this embodiment is sodium chloride, potassium chloride, or a combination thereof. One or more osmotic pressure regulators are present in the range of about 0.005 wt.% to about 1.015 wt.% based on the total weight of the suspension. Based on the total weight of the suspension, one or more osmotic pressure regulators are present in an amount ranging from about 0.005 wt.% to about 1 wt.%. Based on the total weight of the suspension, sodium chloride is present in an amount ranging from about 0.1 wt.% to about 1.0 wt.%. Based on the total weight of the suspension, potassium chloride is present in an amount ranging from about 0.005 wt.% to about 0.015 wt.%. In some other embodiments, the buffer according to this embodiment is dipotassium phosphate and disodium hydrogen phosphate. Based on the total weight of the suspension, the buffer is present in an amount ranging from about 0.005 wt.% to about 0.115 wt.%. Based on the total weight of the suspension, the buffer is present in an amount ranging from about 0.005 wt.% to about 0.1 wt.%. Based on the total weight of the suspension, the buffer dipotassium phosphate is present in an amount ranging from about 0.005 wt.% to about 0.015 wt.%, and disodium hydrogen phosphate is present in an amount ranging from 0.01 to 0.1 wt.%.The solvent according to this embodiment is water for injection. Based on the total weight of the suspension, the solvent is present in an amount ranging from about 60 wt.% to about 80 wt.%.

[0307] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 1 wt.% to about 40 wt.% based on the total weight of the microspheres. In another embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 10 wt.% to about 25 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant. The suspension of this embodiment has an average particle size of microspheres in the range of about 1 µm to 120 µm. The suspension of this embodiment has an average particle size of microspheres not greater than 90 µm. The suspension of this embodiment has an average particle size of microspheres in the range of about 10 µm to 80 µm.

[0308] The microspheres in the suspension are substantially uniform in size and shape. For example, about 70% of the drug-loaded microspheres in the suspension have an average particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0309] One embodiment of the present invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant.

[0310] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant.

[0311] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant and a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 120 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0312] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant and a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 120 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0313] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant and a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 100 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have an average particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0314] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant and a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 100 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have an average particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0315] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 30 µm to 80 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0316] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 10 µm to 80 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0317] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 30 µm to 80 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0318] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 10 µm to 80 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0319] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 80 µm to 120 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0320] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 80 µm to 120 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 80% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0321] Another embodiment of the invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 40 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0322] One embodiment of the present invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 40 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0323] One embodiment of the present invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase optionally contains a surfactant. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 40 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 75% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0324] One embodiment of the present invention provides a long-acting parenteral pharmaceutical composition of telpolide, wherein telpolide is present in the range of about 10 wt.% to about 25 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase optionally contains a surfactant. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 40 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension. Another embodiment of the present invention provides a long-acting parenteral pharmaceutical composition of retaglutide, wherein retaglutide is present in the range of about 1 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant and a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 120 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0325] One aspect of the present invention provides a long-acting parenteral pharmaceutical composition comprising a stable formulation of an active pharmaceutical ingredient (API), wherein one or more active pharmaceutical ingredients (APIs) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of about 3 wt.% to about 10 wt.% (based on the total weight of the microparticles / microspheres, about 10 wt.% to about 40 wt.%).

[0326] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of about 0.1 wt.% to about 3 wt.% (based on the total weight of the microspheres, about 1 wt.% to about 10 wt.%). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres) based on the total weight of the suspension. The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0327] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in an amount ranging from 3 wt.% to about 10 wt.% based on the total weight of the suspension (from about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0328] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the APIs selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of about 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used, which is a lactic acid:glycolic acid ratio between 70:30 and 85:15. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0329] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of about 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 80. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0330] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 80. The surfactant is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0331] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polyvinyl alcohol. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0332] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in an amount ranging from 3 wt.% to about 10 wt.% based on the total weight of the suspension (from about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in an amount ranging from about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used, which is a lactic acid:glycolic acid ratio between 70:30 and 85:15. The surfactant according to this embodiment is polyvinyl alcohol. The surfactant is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. Based on the total weight of the suspension, the suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.%. The osmotic pressure regulator according to this embodiment is sodium chloride. Based on the total weight of the suspension, the osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.%. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. Based on the total weight of the suspension, the buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.%. The solvent according to this embodiment is water for injection. Based on the total weight of the suspension, the solvent is present in an amount ranging from about 60 wt.% to about 80 wt.%.

[0333] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is carboxymethyl cellulose. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0334] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is carboxymethyl cellulose. The suspending agent is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0335] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 1 wt.% to about 10 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0336] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0337] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is mannitol. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0338] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is mannitol. The osmotic pressure regulator is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0339] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0340] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is disodium hydrogen phosphate and sodium hydroxide. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0341] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is disodium hydrogen phosphate and sodium hydroxide. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0342] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is disodium hydrogen phosphate and sodium hydroxide. The buffer is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The solvent according to this embodiment is water for injection. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0343] Another aspect of the invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more of the active pharmaceutical ingredient (API) selected from retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the suspension (about 10 wt.% to about 40 wt.% based on the total weight of the microspheres). The biodegradable polymer according to this embodiment is PLGA. The amount of PLGA is in the range of about 25 wt.% to about 45 wt.% based on the total weight of the suspension (present in the range of about 55 wt.% to about 95 wt.% based on the total weight of the microspheres). The composition of PLGA is described based on the molar ratio of the monomers used. This composition ratio is a lactate:glycolic acid ratio between 70:30 and 85:15. In another embodiment, the composition ratio is a lactate:glycolic acid ratio of 50:50. In some embodiments, the composition ratio is a lactic acid:glycolic acid ratio of 75:25. In some embodiments, the biodegradable polymer is PLA. The surfactant according to this embodiment is polysorbate 20. The surfactant is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The suspending agent according to this embodiment is polyethylene glycol. The suspending agent is present in an amount ranging from about 1 wt.% to about 5 wt.% based on the total weight of the suspension. The osmotic pressure regulator according to this embodiment is sodium chloride. The osmotic pressure regulator is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The buffer according to this embodiment is sodium dihydrogen phosphate monohydrate and citric acid. The buffer is present in an amount ranging from about 0.1 wt.% to about 1 wt.% based on the total weight of the suspension. The solvent according to this embodiment is pure water. The solvent is present in an amount ranging from about 60 wt.% to about 80 wt.% based on the total weight of the suspension.

[0344] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more APIs, namely retaglutide, semaglutide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide, are present in the range of 1 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 120 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have an average particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0345] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more active pharmaceutical ingredients (APIs) such as retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant.

[0346] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more active pharmaceutical ingredients (APIs) such as retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant.

[0347] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more APIs—retaglutide, semaglutide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide—are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant and a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 120 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0348] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more APIs, namely retaglutide, semaglutide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide, are present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant and a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 120 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0349] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more APIs—retaglutide, semaglutide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide—are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains surfactants and buffers. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 100 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have an average particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0350] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more APIs, namely retaglutide, semaglutide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide, are present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant and a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 100 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have an average particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0351] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more APIs—retaglutide, semaglutide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide—are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 30 µm to 80 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0352] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more APIs, namely retaglutide, semaglutide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide, are present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 30 µm to 80 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0353] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more APIs—retaglutide, semaglutide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide—are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 80 µm to 120 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0354] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more APIs, namely retaglutide, semaglutide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide, are present in the range of about 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a buffer. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 80 µm to 120 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 80% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0355] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more APIs—retaglutide, semaglutide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide—are present in the range of 3 wt.% to about 10 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 40 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0356] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more APIs, namely retaglutide, seminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide, are present in the range of 10 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase contains a surfactant. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 40 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0357] In one embodiment, the present invention provides a long-acting parenteral pharmaceutical composition of an active pharmaceutical ingredient (API), wherein one or more active pharmaceutical ingredients (APIs) selected from telpotetide, retaglutide, sminotropicide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide are present in the range of 4 wt.% to about 40 wt.% based on the total weight of the microspheres. The microspheres are prepared using a w / o / w emulsion technique, wherein the internal aqueous phase optionally contains a surfactant. The average particle size of the microspheres in the suspension of this embodiment is in the range of about 1 µm to 120 µm. The microspheres in the suspension are substantially uniform in size and shape; for example, about 70% of the drug-loaded microspheres in the suspension have a particle size within (+ / -) 10% of the average particle size of the drug-loaded microspheres in the suspension.

[0358] In one aspect, a composition characterized by any one or more of the aspects provided above is provided, wherein the composition is further characterized by: lacking one or more components of the composition described in any one or more of WO2023281495, WO2010028257, EP4205728, WO2022003662 or any reference cited in the background section of this disclosure, or having a composition in which the amount of one or more components is significantly different or considerably different from the amount of one or more components described therein. Attached Figure Description

[0359] Figure 1 SEM images showing the internal morphology of microspheres loaded with telpoeptide are provided.

[0360] Figure 2 SEM images showing the external morphology of microspheres loaded with telpoeptide at different magnifications are provided.

[0361] Figure 3 In vitro release data of the microspheres loaded with telpoeptide are provided in buffer systems at 45°C and pH 7 and pH 9, and in buffer system at 37°C and pH 7.4.

[0362] Figure 4 The volume-average diameter of the microsphere formulation loaded with telpoide is provided, measured by the Coulter counter method. Detailed Implementation

[0363] For convenience, combinations of elements / steps as well as individual elements / steps may be described in this part of the disclosure. Although paragraphs focusing on specific elements / steps are included, any aspect, level, implementation, or other description of a specific step or element may be applied to any general description of the compositions / methods of the invention, or any other elements / steps referenced therein, which are provided in any part of this disclosure.

[0364] As used herein, the term "exemplary" means "serving as an example, instance, or illustration." The following detailed description is exemplary in nature only and is not intended to limit the application and use. Any implementation described herein as "exemplary" should not necessarily be construed as being more preferred or advantageous than other implementations.

[0365] There is a need to develop long-acting injectable formulations of drugs such as melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) receptor agonists and / or GLP-1 and / or GIP and / or glucagon receptor agonists, which provide release of such drugs over a sustained period of time, exceeding one month or even several months. The pharmaceutical compositions of the present invention provide patient compliance and predictable and stable plasma levels.

[0366] The inventors have unexpectedly identified compositions comprising microparticles of one or more APIs, which can be characterized as agonists of one or more of the melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors, or agonists of one or more of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon receptors, or combinations thereof, which, when provided in formulations for parenteral administration, provide controlled, long-acting drug release. In embodiments, the compositions and formulations provided herein may: (1) comprise components and constituent elements; be prepared by methods / processes; be used in therapeutic applications; and, for example, be components of a kit, all of which are described herein.

[0367] The inventors have unexpectedly identified compositions comprising microparticles of one or more APIs selected from telpolide, retaglutide, sminolide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide, or combinations thereof, which, when provided in a formulation for parenteral administration, provide controlled, long-acting drug release. In embodiments, the compositions and formulations provided herein may: (1) comprise components and constituent elements; be prepared by a method / process; be used in a treatment method; and, for example, be a component of a kit, all of which are described herein. The reference to “composition” herein is generally used to describe a population of microparticles (microparticle composition or microparticle group). The term “composition” may be used to refer to a composition of individual specific microparticles (e.g., in the absence of a solvent component) or when present as a component of a formulation (e.g., in the presence of a solvent component). When such a composition is a component of a formulation, the characteristics of the “composition” described herein should be interpreted as characteristics of the formulation. The term "formulation" as used in this article is generally used to describe a particulate composition plus a solvent such that the formulation is an administerable form, for example, a form suitable for parenteral administration to mammalian recipients. Compositions and Formulations Particulate Composition

[0368] In some aspects, the present invention provides compositions comprising microparticles of one or more APIs, wherein the microparticles provide controlled, long-term release of such APIs. In some aspects, the microparticle compositions provided herein are long-acting, parenteral-administered compositions comprising an API component and a carrier component.

[0369] In some aspects, the present invention provides a long-acting parenteral pharmaceutical composition comprising a microparticle population comprising (1) an API component comprising GLP-1 and / or glucagon and / or GIP agonists or other incretin agonists or melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) receptor agonists or other melanocortin agonists; (2) a carrier component comprising one or more biodegradable polymers; and (3) a surfactant component comprising one or more surfactants. In some aspects, one or more components or constituents thereof may be at least partially or, for example, entirely present (as part of) one or more other components. For example, in some aspects, the surfactant component may be contained in or be a constituent of the carrier component.

[0370] In this document, “GLP-1 and / or glucagon and / or GIP agonist” refers to one or more compounds that provide one or more such agonist activities. For example, “GLP-1 and / or glucagon and / or GIP agonist” may refer to one or more compounds, each exhibiting one of GLP-1 agonist activity, glucagon receptor activity, or GIP agonist activity; or, for example, “GLP-1 and / or glucagon and / or GIP agonist” may refer to one or more compounds, each exhibiting two or more of GLP-1 agonist activity, glucagon receptor activity, and GIP agonist activity.

[0371] In this document, “melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) receptor agonists” refers to one or more compounds that provide one or more such agonist activities. For example, “melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) receptor agonists” may refer to one or more compounds, wherein each compound exhibits one of the melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors; or, for example, “melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors”. "Melanin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) receptor agonists" can refer to one or more compounds, each of which exhibits two or more of the following melanocortin-1 (MC1) activity, melanocortin-2 (MC2) activity, melanocortin-3 (MC3) activity, melanocortin-4 (MC4) activity, and melanocortin-5 (MC5) receptor activity.

[0372] In some aspects, the present invention provides long-acting parenteral pharmaceutical compositions comprising a microparticle population comprising (1) an API component comprising GLP-1 and / or glucagon and / or GIP agonists and / or melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) receptor agonists; (2) a carrier component comprising one or more biodegradable polymers; (3) a surfactant component comprising one or more surfactants; (4) a suspension component comprising one or more suspending agents; (5) an osmotic component comprising one or more osmotic agents; (6) a buffer component; and (7) a solvent component comprising one or more solvents to form a formulation, which is further described elsewhere herein. As described above, in some aspects, one or more components or constituent elements thereof may be present at least partially or, for example, entirely, within one or more other components (forming a part thereof). For example, in some respects, the suspension component may be contained in or be a component of the solvent component.

[0373] In some aspects, the present invention provides long-acting parenteral pharmaceutical compositions comprising a microparticle population comprising (1) one or more APIs selected from telpolide, retaglutide, sminolide, pervitide, lixinatide, dulaglutide, liraglutide, and abiglutide; (2) a carrier component comprising one or more biodegradable polymers; (3) a surfactant component comprising one or more surfactants; (4) a suspension component comprising one or more suspending agents; (5) an osmotic component comprising one or more osmotic agents; (6) a buffer component; and (7) a solvent component comprising one or more solvents to form a formulation, which is further described elsewhere herein. As described above, in some aspects, one or more components or constituents thereof may be at least partially or, for example, entirely, present (as part of) one or more other components. For example, in some aspects, the suspension component may be contained in or be a constituent of the solvent component. Active pharmaceutical ingredients (Methods of exerting agonist activity / agonist methods)

[0374] In one aspect, the present invention provides compositions comprising a microparticle population, wherein the microparticles comprise an API component. One or more APIs, wherein the API comprises one or more of a melanocortin-1 receptor (MC1) agonist, a melanocortin-2 receptor (MC2) agonist, a melanocortin-3 receptor (MC3) agonist, a melanocortin-4 receptor (MC4) agonist, a melanocortin-5 receptor (MC5) agonist, a GLP-1 agonist, a glucagon receptor agonist, and a GIP agonist, or a compound exhibiting activity on two or more of the activities of a GLP-1 agonist, a glucagon receptor agonist, and a GIP agonist, or a compound exhibiting activity on two or more of the melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptor agonists. Active pharmaceutical ingredient (API)

[0375] According to some aspects, the compositions provided herein comprise an API component containing one or more APIs (e.g., peptide APIs). In one aspect, the compositions of the present invention, such as particulate compositions and formulations comprising such particulate compositions, are characterized, among other things, that most, substantially all, substantially all, or all of the peptide-active pharmaceutical ingredient compounds of the particulates have a molecular weight of at least about 1000 Da, for example at least about about 1100 Da, about 1200 Da, about 1300 Da, about 1400 Da, about 1500 Da, about 1600 Da, about 1700 Da, about 1800 Da, or at least about about 1900 Da. In one aspect, the compositions of the present invention, such as particulate compositions and formulations comprising such particulate compositions, are characterized, among other things, that the molecular weight of most, substantially all, substantially all, or all of the peptide-active pharmaceutical ingredient compounds of the particulates is at least about 2000 Da, for example at least about about 2100 Da, about 2200 Da, about 2300 Da, about 2400 Da, about 2500 Da, about 2600 Da, about 2700 Da, about 2800 Da, or at least about about 2900 Da. In another aspect, the compositions of the present invention, such as particulate compositions and formulations comprising such particulate compositions, are characterized, among other things, that the molecular weight of most, substantially all, substantially all, or all of the peptide-active pharmaceutical ingredient compounds of the particulates is at least about 3000 Da, for example at least about 3100 Da, about 3200 Da, about 3300 Da, about 3400 Da, about 3500 Da, about 3600 Da, about 3700 Da, about 3800 Da, or at least about 3900 Da. In some respects, the molecular weight of most, substantially all, substantially all or most of the particles in the composition, the molecular weight of most, substantially all, substantially all or all of the APIs is at least about 4000 Da, for example at least about about 4100 Da, about 4200 Da, about 4300 Da, about 4400 Da, about 4500 Da, about 4600 Da, 4700 Da, 4800 Da, or at least about 4900 Da.

[0376] In some respects, the molecular weight of most, substantially all, substantially all, or all of the APIs in the composition is about 1000 Da to about 5000 Da, about 1200 Da to about 5000 Da, about 1400 Da to about 5000 Da, about 1600 Da to about 5000 Da, about 1800 Da to about 5000 Da, about 2000 Da to about 5000 Da, about 2200 Da to about 5000 Da, about 24 00Da - approximately 5000Da, approximately 2600Da - approximately 5000Da, approximately 2800Da - approximately 5000Da, approximately 3000Da - approximately 5000Da, approximately 3200Da - approximately 5000Da, approximately 3400Da - approximately 5000Da, approximately 3500Da - approximately 5000Da, approximately 3600Da - approximately 4850Da, approximately 3700Da - approximately 4700Da, approximately 3800Da - approximately 4600Da, approximately 3900Da - approximately 4500Da.

[0377] In some respects, the molecular weight of most, substantially all, substantially all or most of the particles in the composition, the API, is about 4250 Da to about 5000 Da, about 4300 Da to about 4950 Da, about 4350 Da to about 5950 Da, about 4400 Da to about 5000 Da, about 4500 Da to about 5000 Da, about 4600 Da to about 5000 Da, or, for example, about 4650-4850 Da.

[0378] According to some aspects, the compositions provided herein (and by default, formulations comprising such compositions; it should be understood accordingly throughout this disclosure) may comprise one or more agonists of glycemic control hormones. In some aspects, the compositions comprise one or more APIs, for example, one or more antidiabetic APIs for the treatment of type 2 diabetes; one or more APIs for the treatment of obesity; one or more APIs for the detectable or significant improvement of glycemic control; or any or all of these combinations.

[0379] In some respects, APIs are water-soluble. GLP-1, glucagon, and GIP are hormones involved in blood glucose control. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are representative gastrointestinal hormones and neuronal hormones that participate in controlling blood glucose levels based on food intake. Glucagon is a peptide hormone secreted by the pancreas that participates in controlling blood glucose levels.

[0380] GLP-1 is a hormone secreted by the small intestine in response to food intake. GLP-1 promotes insulin secretion from the pancreas and inhibits glucagon secretion in a glucose-dependent manner, thereby helping to lower blood sugar levels. In addition, GLP-1 slows down digestion in the gastrointestinal tract by acting as a satiety factor and reduces food intake by delaying the emptying of the digestive tract.

[0381] GIP, like GLP-1, is a gastrointestinal hormone secreted in response to food intake. It is a 42-amino acid hormone secreted by intestinal K cells. GIP is reported to promote insulin secretion from the pancreas in a blood sugar-dependent manner and help lower blood sugar levels, thereby exhibiting effects such as increased GLP-1 activation and anti-inflammatory properties.

[0382] When blood sugar levels drop due to factors such as medication, disease, hormone deficiency, or enzyme deficiency, glucagon is produced in the pancreas. Glucagon signals the liver to break down glycogen, inducing the release of glucose and raising blood sugar levels back to normal. In addition to increasing blood sugar levels, glucagon also suppresses appetite in animals and humans and activates hormone-sensitive lipases in fat cells to promote fat breakdown and energy expenditure, thus exhibiting an anti-obesity effect.

[0383] In some respects, the compositions and formulations described herein comprise one or more glucagon-like peptide-1 (GLP-1) agonists; one or more glucose-dependent insulinotropic peptide (GIP) agonists; one or more glucagon receptor agonists; any or all of these combinations; or compounds exhibiting multiple such agonist activities. A family of melanocortin receptor types and subtypes have been identified, including melanocortin-1 receptor (MC1) expressed on normal human melanocytes and melanoma cells, melanocortin-2 receptor (MC2) expressed in adrenal cells for ACTH (adrenocorticotropic hormone), melanocortin-3 and melanocortin-4 receptors (MC3 and MC4) expressed primarily in cells of the hypothalamus, midbrain, and brainstem, and melanocortin-5 receptor (MC5) expressed extensively in peripheral tissues. MC1 has been identified as being associated with hair and skin pigmentation and inflammation; MC2 is believed to mediate steroid production; MC3 is believed to be associated with energy homeostasis, food intake, and inflammation; MC4 is believed to control eating behavior, energy homeostasis, and sexual function (e.g., erectile function); and MC5 is believed to be involved in the exocrine gland system. Compounds specific to MC3, MC4, or MC5 are believed to be used to regulate energy homeostasis, including as drugs to reduce food intake and weight gain, for the treatment of anorexia, as weight-gain aids, for the treatment of obesity, and for other therapeutic purposes related to food intake and metabolism. In some respects, most, substantially all, substantially all, or all of the APIs in the compositions and formulations described herein are ligands for at least one (if not two or more) endogenous molecule / target (e.g., for glucagon receptor, glucose-dependent insulinotropic peptide receptor, and GLP-1 receptor).

[0384] In some respects, most, substantially all, substantially all, or all of the APIs in the compositions and formulations described herein are ligands of at least one (if not two or more) endogenous molecules / targets (e.g., for melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors).

[0385] In some respects, most, substantially all, substantially all, or all of the APIs in the compositions and formulations described herein are ligands for at least one (if not two or more) endogenous molecules / targets (e.g., for melanocortin-1 receptor (MC1), melanocortin-2 receptor (MC2), melanocortin-3 receptor (MC3), melanocortin-4 receptor (MC4), melanocortin-5 receptor (MC5), glucagon receptor, glucose-dependent insulinotropic peptide receptor, and GLP-1 receptor).

[0386] In this respect, such ligands typically exhibit detectable or significant binding to such molecules / targets (which are usually receptors; therefore, the term receptor in this document is used interchangeably with other ligands and as a concurrent disclosure of other ligands, and vice versa). In some respects, such APIs exhibit DOS biological / physiological responses associated with such binding. In some respects, APIs exhibit at least about 80%, at least about 85%, at least about 95%, or about 100% of the activity of APIs administered in a “free” phase (i.e., not associated with the particle). In some respects, particle APIs maintain such levels of binding potency over sustained time periods (e.g., at least 3, 6, 9, 12, 15, or 18 months after administration).

[0387] In some respects, the API present in the compositions herein may comprise a GLP-1 and / or glucagon and / or GIP agonist selected from the following: (1) an API as a GLP-1 agonist; (2) an API as a glucagon / glucagon receptor agonist; (3) an API as a GIP agonist; (4) an API as both a GLP-1 agonist and a glucagon / glucagon receptor agonist; an API as both a GLP-1 agonist and a GIP agonist; (5) an API as both a glucagon / glucagon receptor agonist and a GIP agonist; or (6) an API as a GLP-1 agonist, a glucagon / glucagon receptor agonist, and a GIP agonist.

[0388] In some respects, the API present in the compositions herein may comprise melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) receptor agonists.

[0389] In some respects, the API present in the compositions herein may include (1) an API as a melanocortin-1 receptor (MC1) agonist, (2) an API as a melanocortin-2 receptor (MC2) agonist, (3) an API as a melanocortin-3 receptor (MC3) agonist, (4) an API as a melanocortin-4 receptor (MC4) agonist, and (5) an API as a melanocortin-5 receptor (MC5) agonist.

[0390] In some aspects, the compositions provided by the present invention comprise a single API, wherein the single API exhibits detectable or significant agonist activity against only one of GLP-1, glucagon receptor, and GIP.

[0391] In some aspects, the compositions provided by the present invention comprise a single API, wherein the single API exhibits detectable or significant agonist activity against only one of the melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors.

[0392] In some respects, the composition comprises two or more APIs, each of which exhibits detectable or significant agonist activity against only one of GLP-1, glucagon receptor, and GIP.

[0393] In some respects, the composition contains two or more APIs, each of which exhibits detectable or significant agonist activity against only one of the melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors.

[0394] In some respects, the composition comprises a single API, wherein the single API exhibits detectable or significant agonist activity against two or more of GLP-1, glucagon receptor, and GIP.

[0395] In some aspects, the composition comprises a single API, wherein the single API exhibits detectable or significant agonist activity against two or more of the melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors.

[0396] In some respects, the composition comprises two or more APIs, each of which exhibits detectable or significant agonist activity against two or more of GLP-1, glucagon receptor, and GIP.

[0397] In some aspects, the composition comprises two or more APIs, each of which exhibits detectable or significant agonist activity against two or more of the melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors.

[0398] In some aspects, the composition comprises two or more APIs, wherein at least one of the two or more APIs exhibits detectable or significant activity against only one of GLP-1, glucagon receptor and GIP, and at least another of the two or more APIs exhibits detectable or significant activity against two or more of GLP-1, glucagon receptor and GIP.

[0399] In some aspects, the composition comprises two or more APIs, wherein at least one of the two or more APIs exhibits detectable or significant activity against only one of the melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors, and at least another of the two or more APIs exhibits detectable or significant activity against two or more of the melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptors. GLP-1 agonists (GLP-1 activation mechanisms)

[0400] According to some aspects, the compositions provided herein comprise an API component containing one or more APIs that provide detectable or significant GLP-1 agonist activity. In some aspects, the compositions provided herein comprise an API component containing one or more APIs that function as GLP-1 analogs; that is, the API functionally mimics the action of human incretin glucagon-like peptide-1 (GLP-1), resulting in a detectable or significant increase in insulin secretion, a detectable or significant increase in glycemic handling, a detectable or significant improvement in glycemic control, or any or all of these. In some aspects, the compositions provided herein comprise an API component containing a means for activating GLP-1. In some aspects, the compositions provided herein comprise a GLP-1 activating means. According to some aspects, the compositions provided herein comprise an API component containing one or more APIs that provide detectable or significant GLP-1 agonist activity, i.e., a means for activating GLP-1, such as lixisenatide, dulaglutide, liraglutide, abiglutide, retaglutide, pervitide, or telposide. In some respects, the compositions provided herein include API components comprising lixisenatide, dulaglutide, liraglutide, abiglutide, retaglutide, peptidase or telpoglutide, or any or a combination of all of these.

[0401] In some aspects, the compositions provided herein comprise an API component comprising one or more APIs that exhibit detectable or significant GLP-1 agonist activity but do not exhibit detectable or significant GIP agonist activity, glucagon receptor agonist activity, or both, such as lixinatide, dulaglutide, liraglutide, abiglutide, etc. In some aspects, the compositions provided herein comprise an API component comprising lixinatide, dulaglutide, liraglutide, abiglutide, or any or all combinations thereof.

[0402] In some respects, the compositions do not contain any API that exhibits detectable or significant GLP-1 agonist activity but does not exhibit detectable or significant glucagon receptor agonist activity, GIP agonist activity, or both. For example, in some respects, the compositions provided herein do not contain lixisenatide, dulaglutide, liraglutide, or abiglutide, or any or any combination of all of these. Glucagon receptor agonists (glucagon receptor activation mechanisms)

[0403] In some aspects, the compositions provided herein comprise an API component containing one or more APIs that provide detectable or significant glucagon receptor agonist activity. In some aspects, the compositions provided herein comprise an API component containing one or more APIs capable of detectably or significantly activating the glucagon receptor by mimicking the action of the human hormone glucagon. In some aspects, the compositions provided herein comprise an API component containing one or more means for activating the glucagon receptor. In some aspects, the compositions provided herein comprise an API component containing a glucagon receptor activation means. In some aspects, the compositions provided herein comprise an API component containing one or more APIs that provide detectable or significant glucagon receptor agonist activity, i.e., means for activating the glucagon receptor, i.e., glucagon receptor activation means, such as retaglutide, pervitin, etc. In some aspects, the compositions provided herein comprise an API component containing retaglutide, pervitin, or a combination thereof.

[0404] In some respects, the compositions provided herein do not contain any API that exhibits detectable or significant GLP-1 agonist activity, detectable or significant GIP agonist activity, or both, but does not exhibit detectable or significant glucagon receptor agonist activity. For example, in some respects, the compositions provided herein do not contain lixisenatide, dulaglutide, liraglutide, abiglutide, or, for example, telposide.

[0405] In some aspects, the compositions provided herein do not contain any API that exhibits detectable or significant glucagon receptor agonist activity and detectable or significant GLP-1 activity, but does not exhibit detectable or significant GIP agonist activity. For example, in some aspects, the compositions provided herein do not contain peptidyl peptide. In some aspects, the compositions provided herein include an API component comprising retaliglutide. GIP agonists (GIP activation methods)

[0406] According to some aspects, the compositions provided herein comprise an API component containing one or more APIs that provide detectable or significant GIP agonist activity. In some aspects, the compositions provided herein comprise an API component containing a means for activating GIP. In some aspects, the compositions provided herein comprise a GIP activating means. According to some aspects, the compositions provided herein comprise an API component containing one or more APIs that provide detectable or significant GIP agonist activity, i.e., a means for activating GIP, i.e., a GIP activating means, such as retaglutide, telposide, etc. In some aspects, the compositions provided herein comprise an API component containing retaglutide, telposide, or a combination thereof.

[0407] In some aspects, the compositions provided herein comprise an API component containing one or more APIs that exhibit detectable or significant GIP agonist activity but not detectable glucagon receptor agonist activity, such as telpolide. In some aspects, the compositions provided herein comprise an API component containing retaliglutide.

[0408] In some respects, the compositions provided herein do not contain any API that exhibits detectable or significant GLP-1 agonist activity, glucagon receptor agonist activity, or both, but does not exhibit detectable or significant GIP agonist activity. For example, in some respects, the compositions do not contain lixisenatide, dulaglutide, liraglutide, abiglutide, or pervitide. Multi-target agonists (multi-target agonist approach)

[0409] In some aspects, the compositions provided herein comprise an API component containing one or more APIs, each API providing detectable or significant agonist activity against two or more of GLP-1, glucagon receptor, and GIP. In some aspects, the compositions provided herein, for example, particulate compositions comprising one or more such APIs (e.g., retaliglutide, telposide, or both), unexpectedly exhibit agonist activity against two or more of GLP-1, glucagon / glucagon receptor, and GIP when provided in such forms. In some aspects, the particulate compositions provide APIs, such as retaliglutide, telposide, or, for example, one or more APIs described herein, which exhibit agonist activity against GLP-1, glucagon receptor, and GIP over extended time periods (e.g., at least about 1 month, e.g., at least about 3, about 6, about 9, or, e.g., at least about 12 months). In some aspects, the compositions provided herein comprise an API component containing a means for activating two or more of GLP-1, glucagon receptor, and GIP. In some aspects, the compositions provided herein comprise a GLP-1 and glucagon receptor activation mechanism; a GLP-1 and GIP activation mechanism; a glucagon receptor and GIP activation mechanism; a GLP-1, glucagon receptor, and GIP activation mechanism; or any or all of these combinations. According to some aspects, the compositions provided herein comprise an API component comprising one or more APIs (e.g., peptide APIs) that provide detectable or significant agonist activity against two or more of GLP-1, glucagon receptor, and GIP, such as retaglutide, telposide, etc. In some aspects, the compositions provided herein comprise an API component comprising retaglutide, telposide, or any or all of these combinations.

[0410] In some aspects, the compositions provided herein comprise an API component containing one or more APIs exhibiting detectable or significant GLP-1 agonist activity and detectable or significant glucagon receptor agonist activity, such as retaglutide, pervitin, etc. In some aspects, the compositions provided herein comprise an API component containing retaglutide, pervitin, or both.

[0411] In some aspects, the compositions provided herein comprise an API component containing one or more APIs exhibiting detectable or significant GLP-1 agonist activity and detectable or significant GIP agonist activity, such as retaglutide, telposide, etc. In some aspects, the compositions provided herein comprise an API component containing retaglutide, telposide, or both.

[0412] In some respects, the compositions provided herein do not contain any API that does not exhibit detectable or significant activity against two or more of GLP-1, glucagon receptor, and GIP, such as lixisenatide, dulaglutide, liraglutide, or abiglutide.

[0413] In some aspects, the compositions provided herein comprise an API component containing one or more APIs that exhibit detectable or significant agonist activity against two or more of GLP-1, glucagon receptor, and GIP, but not detectable or significant agonist activity against each of GLP-1, glucagon receptor, and GIP, such as pervitin, telposide, etc. In some aspects, the compositions provided herein comprise an API component containing pervitin, telposide, or both.

[0414] In some aspects, the compositions provided herein comprise an API component containing one or more APIs that exhibit detectable or significant agonist activity against each of GLP-1, glucagon receptor, and GIP, for example, retaglutide. In one specific aspect of the invention, a stable, long-acting-release particulate formulation of a glucagon-like peptide-1 (GLP-1) agonist and / or a glucagon receptor agonist and / or a glucose-dependent insulinotropic peptide (GIP) agonist is provided. In some aspects, the compositions provided herein comprise an API component containing retaglutide.

[0415] In some aspects, the compositions provided herein comprise an API component containing one or more APIs that exhibit detectable or significant GLP-1 and GIP agonist activity, but do not exhibit detectable glucagon receptor agonist activity, such as telpolide. In some aspects, the compositions provided herein comprise an API component containing telpolide.

[0416] In some aspects, the compositions provided herein comprise an API component containing one or more APIs that exhibit detectable or significant GLP-1 and glucagon receptor activity, but do not exhibit detectable or significant GIP agonist activity, such as pervitin. In some aspects, the compositions provided herein comprise an API component containing pervitin. Melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4), and melanocortin-5 (MC5) receptor agonists (Activation mechanisms of melanocortin-1 (MC1), melanocortin-2 (MC2), melanocortin-3 (MC3), melanocortin-4 (MC4) and melanocortin-5 (MC5) receptors)

[0417] According to some aspects, the compositions provided herein comprise an API component containing one or more APIs that provide detectable or significant MC1, MC2, MC3, MC4, and MC5 receptor agonist activity. In some aspects, the compositions provided herein comprise an API component containing a means for activating MC1, MC2, MC3, MC4, and MC5 receptors. In some aspects, the compositions provided herein comprise MC1, MC2, MC3, MC4, and MC5 receptor activation means. According to some aspects, the compositions provided herein comprise an API component containing one or more APIs that provide detectable or significant MC4 agonist activity, i.e., a means for activating the MC4 receptor, i.e., an MC4 activation means, such as semanotide, etc. In some aspects, the compositions provided herein comprise an API component containing semanotide. In some aspects, the compositions provided herein comprise an API component containing one or more APIs that exhibit detectable or significant MC4 receptor agonist activity but not detectable MC1, MC2, MC3, and MC5 receptor agonist activity, such as semanotide. In some aspects, the compositions provided herein comprise an API component containing semanotide. API Particle Content: API

[0418] According to some aspects, the compositions provided herein comprise an API component containing a single API, and the microparticles in the compositions provided herein contain that single API. In some aspects, the compositions may therefore comprise a single group of microparticles, wherein the microparticles have at least substantially, at least substantially, at least essentially the same or identical content with respect to the API.

[0419] In some aspects, the compositions provided herein comprise an API component containing one or more APIs. In some aspects, the compositions provided herein comprise one or more APIs, for example, one or more APIs selected from the group consisting of telpolide, retaglutide, sminolide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide, wherein a detectable or significant amount of each of at least one or more APIs is present on, within, or otherwise associated with some, most, substantially all, essentially all, or all of the particles of the composition, such that the particles of the composition have at least most, at least substantially, at least substantially, at least substantially the same or identical content with respect to the API. In some aspects, the compositions provided herein comprise particles, wherein at least most, substantially all, substantially all, or substantially all of the particles of the composition comprise the same API.

[0420] In some aspects, the compositions provided herein comprise an API component comprising one or more APIs selected from the group consisting of telpolide, retalolide, sminolide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide, wherein at least one of at least two APIs is provided on, within, or otherwise associated with a first microparticle subpopulation, and at least one of at least two APIs is provided on, within, or otherwise associated with a second microparticle subpopulation.

[0421] In some aspects, the compositions provided herein comprise microparticles, wherein at least a first portion of the microparticles in the composition represents a first microparticle subgroup, and at least a second portion of the microparticles in the composition represents a second microparticle subgroup, wherein at least the first and at least the second microparticle subgroups differ in their API content; for example, at least one microparticle subgroup contains at least one API that is not present in at least another microparticle subgroup.

[0422] In this invention, the composition comprises at least two subgroups of particles, each subgroup representing any percentage of the complete particle population of the composition. For example, in some aspects, the composition may comprise, for instance, two subgroups of particles, wherein the first subgroup represents about 0.1%, 0.5%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more than 95% of the complete particle population (e.g., about 0.1% to at least 95%, e.g., about 0.1% to about 90%, about 0.1% to about 80%, about 0.1% to about 70%, about 0.1% to about 60%, about 0.1% to about 50%, about 0.1% to about 40%, about 0.1% to about 30%, about 0.1% to about 20%, about 0.1% to about 50%, about 0.1% to about 40%, about 0.1% to about 30%, about 0.1% to about 20%, about 0.1% to about 95%). Approximately 10%, or, for example, approximately 0.1% to 5% of the complete population, such as approximately 5% to approximately 95%, approximately 10% to approximately 95%, approximately 20% to approximately 95%, approximately 30% to approximately 95%, approximately 40% to approximately 95%, approximately 50% to approximately 95%, approximately 60% to approximately 95%, approximately 70% to approximately 95%, approximately 80% to approximately 95%, or, for example, approximately 90% to approximately 95% of the complete population, such as approximately 5% to approximately 90%, approximately 10% to approximately 80%, approximately 20% to approximately 70%, approximately 30% to approximately 60%, or, for example, approximately 40% to approximately 50%, and, for example, any value near or included in such ranges as described elsewhere herein), while the second subgroup represents the remainder of the complete microparticle population. Similarly, in some aspects, for example, the composition may contain three or more microparticle subgroups, wherein each microparticle subgroup may represent any fraction of the complete microparticle population, and the combination of subgroups represents the complete microparticle population in the composition. Active pharmaceutical ingredient (API) - dosage

[0423] The API component of the compositions provided herein may be present in any effective amount, for example, any effective amount suitable and effective for treating (e.g., effective for detectably or significantly advantageously altering one or more indicators) a disease state or condition during the treatment period.

[0424] In some respects, the API component of the compositions provided herein may contain an API (API component) in an amount effective for, when administered during an effective therapeutic period, to detectably or significantly treat (e.g., detectably or significantly and advantageously alter one or more indicators) diabetes (e.g., type 2 diabetes) or its associated side effects or conditions.

[0425] The API component of the compositions provided herein may contain an API (API component) in an amount effective for, when administered during an effective therapeutic period, to detectably or significantly treat (e.g., detectably or significantly and advantageously alter one or more indicators) obesity or related side effects, or related conditions.

[0426] The API component of the compositions provided herein may contain an API (API component) in an amount effective for detecting or significantly reducing weight or weight-related conditions when administered during an effective therapeutic period.

[0427] The API component of the compositions provided herein may contain an API (API component) in an amount effective for, when administered during an effective therapeutic period, to detectably or significantly reduce blood glucose levels (i.e., fasting blood glucose levels) or related conditions. The API component of the compositions provided herein may contain an API in an amount effective for detectably or significantly reducing blood glucose levels (i.e., fasting blood glucose levels) by at least about 5% during an effective therapeutic period, for example, ≥ about 6%, ≥ about 8%, ≥ about 10%, ≥ about 15%, ≥ about 20%, ≥ about 25%, ≥ about 30%, ≥ about 35%, ≥ about 40%, ≥ about 45%, or, for example, ≥ about 50%.

[0428] The API component of the compositions provided herein may contain an API (API component) in an amount effective for detectably or significantly reducing hemoglobin A1c (HbA1c) or related conditions when administered during an effective therapeutic period. The API component of the compositions provided herein may contain an API in an amount effective for detectably or significantly reducing HbA1c by at least about 5% during an effective therapeutic period, for example, ≥ about 6%, ≥ about 8%, ≥ about 10%, ≥ about 15%, ≥ about 20%, ≥ about 25%, ≥ about 30%, ≥ about 35%, ≥ about 40%, ≥ about 45%, or, for example, ≥ about 50%.

[0429] According to some aspects, the composition is prepared using a biemulsion preparation method comprising a first phase. In some aspects, the first phase is an aqueous first phase. In some aspects, the composition is prepared using a biemulsion preparation method comprising a first phase, wherein one or more APIs (API components) are present in the first phase at a concentration of about 0.1 wt.% to about 30 wt.%, for example, about 0.1 wt.% to about 28 wt.%, about 0.1 wt.% to about 26 wt.%, about 0.1 wt.% to about 24 wt.%, about 0.1 wt.% to about 22 wt.%, about 0.1 wt.% to about 20 wt.%, or about 0. 1 wt.% to about 18 wt.%, about 0.1 wt.% to about 16 wt.%, about 0.1 wt.% to about 14 wt.%, about 0.1 wt.% to about 12 wt.%, about 0.1 wt.% to about 10 wt.%, about 0.1 wt.% to about 8 wt.%, about 0.1 wt.% to about 6 wt.%, about 0.1 wt.% to about 4 wt.%, or, for example, about 0.1 wt.% to about 2 wt.% are present in the first phase.

[0430] In some aspects, the first phase is an aqueous first phase. In some aspects, the composition is prepared using a biemulsion preparation method comprising the first phase, wherein one or more APIs (API components) are present in the first phase at a concentration of about 0.2 wt.% to about 30 wt.%, for example, about 0.4 wt.% to about 30 wt.%, about 0.6 wt.% to about 30 wt.%, about 0.8 wt.% to about 30 wt.%, about 1 wt.% to about 30 wt.%, about 2 wt.% to about 30 wt.%, about 4 wt.% to about 30 wt.%, about 6 wt.% to about 30 wt.%, about An amount of 8 wt.% to about 30 wt.%, about 10 wt.% to about 30 wt.%, about 12 wt.% to about 30 wt.%, about 14 wt.% to about 30 wt.%, about 16 wt.% to about 30 wt.%, about 18 wt.% to about 30 wt.%, about 20 wt.% to about 30 wt.%, about 22 wt.% to about 30 wt.%, about 24 wt.% to about 30 wt.%, about 26 wt.% to about 30 wt.%, or about 28 wt.% to about 30 wt.% is present in the first phase.

[0431] In some aspects, the first phase is an aqueous first phase. In some aspects, the composition is prepared using a biemulsion preparation method comprising the first phase, wherein one or more APIs (API components) are present in the first phase in an amount of about 0.2 wt.% to about 30 wt.%, for example, about 0.4 wt.% to about 28 wt.%, about 0.6 wt.% to about 26 wt.%, about 0.8 wt.% to about 24 wt.%, about 1 wt.% to about 22 wt.%, about 2 wt.% to about 20 wt.%, about 4 wt.% to about 18 wt.%, about 6 wt.% to about 16 wt.%, about 8 wt.% to about 14 wt.%, or, for example, about 10 wt.% to about 12 wt.%.

[0432] According to certain aspects, the formulations provided by the present invention (e.g., formulations provided as suspensions (e.g., suspensions of compositions of microparticles)) may contain an API (API component) in an amount of about 0.1 wt.% to about 20 wt.% of the suspension, for example, about 0.1 wt.% to about 18 wt.%, about 0.1 wt.% to about 16 wt.%, about 0.1 wt.% to about 14 wt.%, about 0.1 wt.% to about 12 wt.%, about 0.1 wt.% to about 10 wt.%, about 0.1 wt.% to about 8 wt.%, about 0.1 wt.% to about 6 wt.%, about 0.1 wt.% to about 4 wt.%, about 0.1 wt.% to about 3 wt.%, or, for example, about 0.1 wt.% to about 2 wt.%.

[0433] According to certain aspects, the formulations provided by the present invention (e.g., formulations provided as suspensions (e.g., suspensions of compositions of microparticles)) may contain an API (API component) in an amount of about 0.2 wt.% to about 20 wt.%, about 0.4 wt.% to about 20 wt.%, about 0.6 wt.% to about 20 wt.%, about 0.8 wt.% to about 20 wt.%, about 1 wt.% to about 20 wt.%, about 2 wt.% to about 20 wt.%, about 4 wt.% to about 20 wt.%, about 6 wt.% to about 20 wt.%, about 8 wt.% to about 20 wt.%, about 10 wt.% to about 20 wt.%, about 12 wt.% to about 20 wt.%, about 14 wt.% to about 20 wt.%, about 16 wt.% to about 20 wt.%, or about 18 wt.% to about 20 wt.% of the formulation (e.g., the suspension).

[0434] According to certain aspects, the formulations provided by the present invention (e.g., formulations provided as suspensions (e.g., suspensions of a composition of microparticles)) may contain an API (API component) in an amount of about 0.2 wt.% to about 18 wt.% of the formulation (e.g., the suspension), for example, about 0.4 wt.% to about 16 wt.%, about 0.6 wt.% to about 14 wt.%, about 0.8 wt.% to about 12 wt.%, about 1 wt.% to about 10 wt.%, about 2 wt.% to about 10 wt.%, or, for example, about 3 wt.% to about 10 wt.%.

[0435] According to certain aspects, the formulations provided by the present invention (e.g., formulations provided as suspensions (e.g., suspensions of a composition of microparticles)) may contain an API (API component) in an amount of about 1 wt.% to about 50 wt.% of the microparticles, for example, about 1 wt.% to about 45 wt.%, about 1 wt.% to about 40 wt.%, about 1 wt.% to about 35 wt.%, about 1 wt.% to about 30 wt.%, about 1 wt.% to about 25 wt.%, about 1 wt.% to about 20 wt.%, about 1 wt.% to about 15 wt.%, about 1 wt.% to about 10 wt.%, or, for example, about 1 wt.% to about 5 wt.%.

[0436] According to certain aspects, the formulations provided by the present invention (e.g., formulations provided as suspensions (e.g., suspensions of a composition of microparticles)) may contain an API (API component) in an amount of about 2 wt.% to about 50 wt.%, about 5 wt.% to about 50 wt.%, about 10 wt.% to about 50 wt.%, about 15 wt.% to about 50 wt.%, about 20 wt.% to about 50 wt.%, about 25 wt.% to about 50 wt.%, about 30 wt.% to about 50 wt.%, about 35 wt.% to about 50 wt.%, about 40 wt.% to about 50 wt.%, or, for example, about 45 wt.% to about 50 wt.%.

[0437] According to certain aspects, the formulations provided by the present invention (e.g., formulations provided as suspensions (e.g., suspensions of compositions of microparticles)) may contain an API (API component) in an amount of about 2 wt.% to about 48 wt.% of the microparticles, for example, about 4 wt.% to about 46 wt.%, about 6 wt.% to about 44 wt.%, about 8 wt.% to about 42 wt.%, about 10 wt.% to about 40 wt.%, about 12 wt.% to about 38 wt.%, about 14 wt.% to about 36 wt.%, about 16 wt.% to about 34 wt.%, about 18 wt.% to about 32 wt.%, about 20 wt.% to about 30 wt.%, or, for example, about 22 wt.% to about 28 wt.%.

[0438] In some aspects, one or more melanocortin-1 (MC1) and / or melanocortin-2 (MC2) and / or melanocortin-3 (MC3) and / or melanocortin-4 (MC4) and / or melanocortin-5 (MC5) agonists and / or GLP-1 and / or glucagon and / or GIP agonists are present as API components in an amount of about 0.1 wt.% to about 20 wt.% based on the total weight of the formulation provided as a suspension (which is present in an amount of about 1 wt.% to about 50 wt.% based on the total weight of the particles). In some aspects, the API component is present in an amount of about 1 wt.% to about 15 wt.% of the formulation (e.g., a suspension) (about 1 wt.% to about 45 wt.% based on the total weight of the particles).

[0439] In some further aspects, the API component is present in an amount of about 1 wt.% to about 15 wt.% of the formulation (e.g., suspension) (about 1 wt.% to about 40 wt.% based on the total weight of the particles).

[0440] In some further aspects, the API component is present in an amount of about 1 wt.% to about 15 wt.% of the formulation (e.g., suspension) (about 4 wt.% to about 15 wt.% based on the total weight of the particles).

[0441] In some further aspects, the API component is present in an amount of about 3 wt.% to about 10 wt.% of the formulation (e.g., suspension) (about 1 wt.% to about 40 wt.% based on the total weight of the particles). In some further aspects, the API component is present in an amount of about 3 wt.% to about 10 wt.% of the formulation (e.g., suspension) (about 4 wt.% to about 15 wt.% based on the total weight of the particles).

[0442] In some respects, the API component is present in amounts ranging from about 1 wt.% to about 40 wt.% based on the total weight of the particles.

[0443] In some respects, the API component is present in amounts of about 4 wt.% to about 15 wt.% based on the total weight of the particles.

[0444] In a specific respect, the composition contains less than about 10% of any API component (e.g., any one or more APIs present in the formulation), such as ≤ about 9%, ≤ about 8%, ≤ about 7%, ≤ about 6%, ≤ about 5%, ≤ about 4%, ≤ about 3%, ≤ about 2%, or, for example, ≤ about 1% of an API that is not bound to, not attached to, not encapsulated by, or otherwise not associated with the microparticles (e.g., an API that can be characterized as a “free” API). Carrier components (controlled API delivery methods / API delivery methods)

[0445] In some aspects, the compositions provided herein comprise a carrier component. In some aspects, the carrier component provides a means of delivering the API component. In some aspects, the carrier component provides a means of delivering the API component in a controlled manner over a prolonged period of time without a detectable or significant burst release effect, for example, without a detectable or significant initial rapid release of the API. Hereinafter, the term "controlled," as in controlled release or release by a controlled means, means that the average release rate of the API over any consecutive 24-hour period following a single dose differs from the average release rate of the same API over any other 24-hour period following the same single dose by no more than about 20%, for example, no more than about 15%, no more than about 10%, no more than about 5%, and no more than about 1%.

[0446] In some aspects, the particulate compositions provided herein are long-acting, parenteral-administered compositions comprising an API component and a carrier component. In some aspects, the carrier component may comprise any one or more components of an API capable of releasing the API component in a controlled manner over an extended period of time. In some aspects, the carrier component comprises one or more polymers. In some aspects, the carrier component comprises one or more biodegradable polymers, i.e., polymers that degrade over time in vivo or under simulated physiological conditions.

[0447] In some aspects, the compositions provided herein comprise one or more polymers (e.g., one or more biodegradable polymers) comprising, for example, poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), polyethylene glycol (PEG), polycarbonate (PC), polyorthoester (POE), polyesteramide (PEA), N-(2-hydroxypropyl)methacrylamide (HPMA), polyglutamic acid (PGA), polyalkylcyanoacrylate, polycaprolactone (PCL), polyhydroxybutyric acid, polyhydroxyvalerate, polyanhydride, polyhydroxybutyrate-hydroxyvalerate, polylactic acid-polyethylene glycol, polyglycolic acid-polyethylene glycol, polysaccharides, peptides, proteins, etc., or any or all of these, for example, mixtures of these polymers, or, for example, their block copolymers.

[0448] In some aspects, the composition includes a carrier component comprising a single biodegradable polymer. In some aspects, the composition includes a carrier component comprising a combination of two or more polymers. In some aspects, the composition includes a carrier component comprising PLGA. In some aspects, PLGA is the only biodegradable polymer in the carrier component. In some aspects, PLGA is the only polymer in the carrier component. Molar ratio of polymer carrier to PLGA

[0449] In some aspects, formulations, compositions, or microparticles therein include a carrier component comprising a biodegradable polymer (e.g., PLGA). In some aspects, PLGA is characterized according to the molar ratio of its constituent monomers (i.e., lactic acid and glycolic acid). In some aspects, the monomer composition of PLGA in the carrier component is in the range of a lactic acid:glycolic acid ratio of about 50:50 to 100:0 (written alternatively as 50-100:0-50), for example, 50:50, 55:45, 60:40, 65:35, 70:30, 75:25, 80:20, 85:15, 90:10, or, for example, 95:5. In some aspects, the monomer composition of PLGA in the carrier component has a lactate:glycolic acid ratio between approximately 55:45 and approximately 95:5, approximately 75:25 and approximately 25:75, approximately 60:40 and approximately 90:10, approximately 65:35 and approximately 85:15, and approximately 70:30 and approximately 80:20. In other aspects, the monomer composition of PLGA in the carrier component has a lactate:glycolic acid ratio between approximately 50:50 and approximately 75:25. Carrier volume

[0450] Depending on some aspects, the carrier component (or, for example, its constituent elements, such as PLGA) may be present in any effective amount to form microparticles suitable for delivering the API according to the delivery characteristics provided herein.

[0451] In some respects, the microparticles of the compositions provided herein are formed using a dual-emulsion technique, wherein, in the second phase, a carrier material (e.g., a polymer, such as a biodegradable polymer, such as PLGA) is dissolved in a solvent, such as a suitable oil solvent (e.g., the oil phase of the dual-emulsion process).

[0452] In some aspects, the polymer portion of the phase of the dual emulsion may account for about 5 wt.% to about 50 wt.% of that phase (e.g., the second (e.g., the second oil) phase), for example, about 5 wt.% to about 45 wt.%, about 5 wt.% to about 40 wt.%, about 5 wt.% to about 35 wt.%, about 5 wt.% to about 30 wt.%, about 5 wt.% to about 25 wt.%, about 5 wt.% to about 20 wt.%, about 5 wt.% to about 15 wt.%, or, for example, about 5 wt.% to about 10 wt.%.

[0453] In some aspects, the polymer portion of the phase of the dual emulsion may account for about 10 wt.% to about 50 wt.% of that phase (e.g., the second (e.g., the second oil) phase), for example, about 15 wt.% to about 50 wt.%, about 20 wt.% to about 50 wt.%, about 25 wt.% to about 50 wt.%, about 30 wt.% to about 50 wt.%, about 35 wt.% to about 50 wt.%, about 40 wt.% to about 50 wt.%, or, for example, about 45 wt.% to about 50 wt.%.

[0454] In some aspects, the polymer portion of the phase of the dual emulsion may account for about 10 wt.% to about 45 wt.% of that phase (e.g., the second (e.g., the second oil) phase), for example, about 12 wt.% to about 48 wt.%, about 14 wt.% to about 46 wt.%, about 16 wt.% to about 44 wt.%, about 18 wt.% to about 42 wt.%, about 20 wt.% to about 40 wt.%, about 22 wt.% to about 38 wt.%, about 24 wt.% to about 36 wt.%, or, for example, about 26 wt.% to about 34 wt.%.

[0455] In some respects, the polymer portion of the phase of the dual emulsion may account for about 10 wt.% to about 30 wt.% of the phase (e.g., the second (e.g., the second oil) phase), for example, about 12 wt.% to about 28 wt.%, about 14 wt.% to about 26 wt.%, about 16 wt.% to about 24 wt.%, or about 18 wt.% to about 22 wt.% of the polymer-soluble phase.

[0456] In some aspects, the formulation or composition may include a carrier component comprising one or more carrier materials (e.g., one or more polymers, such as one or more biodegradable polymers, such as PLGA), comprising about 10 wt.% to about 70 wt.% of the total weight of the formulation (e.g., a suspension), for example, about 10 wt.% to about 65 wt.%, about 10 wt.% to about 60 wt.%, about 10 wt.% to about 55 wt.%, about 10 wt.% to about 40 wt.%, about 10 wt.% to about 35 wt.%, about 10 wt.% to about 30 wt.%, about 10 wt.% to about 25 wt.%, about 10 wt.% to about 20 wt.%, or, for example, about 10 wt.% to about 15 wt.%.

[0457] In some aspects, the formulation or composition may include a carrier component comprising one or more carrier materials (e.g., one or more polymers, such as one or more biodegradable polymers, such as PLGA), comprising about 15 wt.% to about 70 wt.% of the total weight of the formulation (e.g., a suspension), for example, about 20 wt.% to about 70 wt.%, about 25 wt.% to about 70 wt.%, about 30 wt.% to about 70 wt.%, about 35 wt.% to about 70 wt.%, about 40 wt.% to about 70 wt.%, about 45 wt.% to about 70 wt.%, about 50 wt.% to about 70 wt.%, about 55 wt.% to about 70 wt.%, about 60 wt.% to about 70 wt.%, or, for example, about 65 wt.% to about 70 wt.%.

[0458] In some aspects, the formulation or composition may include a carrier component comprising one or more carrier materials (e.g., one or more polymers, such as one or more biodegradable polymers, such as PLGA), comprising about 15 wt.% to about 65 wt.% of the total weight of the formulation (e.g., a suspension), for example, about 20 wt.% to about 55 wt.%, about 25 wt.% to about 55 wt.%, about 25 wt.% to about 50 wt.%, about 30 wt.% to about 45 wt.%, or, for example, about 35 wt.% to about 40 wt.%.

[0459] In some aspects, the formulation or composition may include a carrier component comprising one or more carrier materials (e.g., one or more polymers, such as one or more biodegradable polymers, such as PLGA) comprising about 55 wt.% to about 95 wt.% of the total weight of the microparticles, for example, about 55 wt.%-90 wt.%, about 55 wt.%-85 wt.%, about 55 wt.%-80 wt.%, about 55 wt.%-75 wt.%, about 55 wt.%-70 wt.%, about 55 wt.%-65 wt.%, or, for example, about 55 wt.%-60 wt.%.

[0460] In some aspects, the formulation or composition may include a carrier component comprising one or more carrier materials (e.g., one or more polymers, such as one or more biodegradable polymers, such as PLGA), comprising about 60 wt.% to about 95 wt.% of the total weight of the microparticles, about 65 wt.% to about 95 wt.%, about 70 wt.% to about 95 wt.%, about 75 wt.% to about 95 wt.%, about 80 wt.% to about 95 wt.%, about 85 wt.% to about 95 wt.%, or, for example, about 90 wt.% to about 95 wt.%.

[0461] In some aspects, the formulation or composition may include a carrier component comprising one or more carrier materials (e.g., one or more polymers, such as one or more biodegradable polymers, such as PLGA) comprising about 60 wt.% to about 90 wt.% of the total weight of the microparticles, for example, about 65 wt.% to about 85 wt.% of the total weight of the microparticles, or for example, about 70 wt.% to about 80 wt.%.

[0462] In some aspects, the formulation or composition may include a carrier component comprising one or more carrier materials (e.g., one or more polymers, such as one or more biodegradable polymers, such as PLGA, PLA) comprising about 75 wt.% to about 90 wt.% of the total weight of the microparticles, for example, about 75 wt.% to about 80 wt.%, about 88 wt.% to about 85 wt.%, or, for example, about 85 wt.% to about 90 wt.% of the total weight of the microparticles.

[0463] In some aspects, the formulation or composition may include a carrier component comprising one or more carrier materials (e.g., one or more polymers, such as one or more biodegradable polymers, such as PLGA, PLA) comprising about 80 wt.% to about 90 wt.% of the total weight of the particles. carrier means

[0464] In this respect, and in relation to any other component / component, the invention may also be characterized as comprising “means” for providing the described function, here meaning to impart / provide to the compositions / formulations of the invention an effective, detectable, or significant carrier (e.g., API carrier) function. In this respect, any known equivalents of such designated reagents may also be incorporated, for example, into the compositions or methods of the invention. As with other similar descriptions herein, any component / component of the invention may be described as a means where appropriate (e.g., the aforementioned carrier or component / component may be described as a carrier means or means for providing effective, detectable, or significant carrier activity / properties to the composition / formulation). Bulk density

[0465] In some respects, the compositions provided herein provide an aggregate of particles. In some respects, the compositions (i.e., the aggregate of particles) can be characterized by the maximum packing density of their particles.

[0466] According to some aspects, as described in detail elsewhere herein, the compositions provided by the present invention comprise particles that are at least substantially, at least substantially...

Claims

1. A method of treating obesity in a patient in need, comprising administering to the patient a long-acting parenteral pharmaceutical composition, the pharmaceutical composition comprising one or more active pharmaceutical ingredients or pharmaceutically acceptable salts thereof and a carrier component, the one or more active pharmaceutical ingredients or pharmaceutically acceptable salts thereof having detectable or significant agonist activity to one or more of the following: melanocortin-1 (MC1) receptor, melanocortin-2 (MC2) receptor, melanocortin-3 (MC3) receptor, melanocortin-4 (MC4) receptor, melanocortin-5 (MC5) receptor, glucagon-like peptide-1 (GLP-1) receptor, glucose-dependent insulinotropic polypeptide (GIP) receptor, glucagon receptor, the carrier component comprising one or more biodegradable polymers, wherein the composition is administered every two weeks to every six months.

2. The method of claim 1, wherein the long-acting parenteral pharmaceutical composition comprises monodisperse microspheres having an average particle size of not more than 120 µm, and at least about 70% of the particles having a particle size within 10% of the average particle size.

3. The method according to claim 1 or 2, wherein the long-acting parenteral pharmaceutical composition comprises monodisperse microspheres having an average particle size of not more than 100 µm, and at least about 70% of the particles having a particle size within 10% of the average particle size.

4. The method according to any one of the preceding claims, wherein the long-acting parenteral pharmaceutical composition comprises monodisperse microspheres having an average particle size of not more than 90 µm, and at least about 70% of the particles having a particle size within 10% of the average particle size.

5. The method according to any one of the preceding claims, wherein the long-acting parenteral pharmaceutical composition comprises monodisperse microspheres having an average particle size between about 30 µm and 80 µm, and at least about 70% of the particles having a particle size within 10% of the average particle size.

6. The method according to any one of the preceding claims, wherein the long-acting parenteral pharmaceutical composition comprises one or more active pharmaceutical ingredients selected from the group consisting of telpolide, retaglutide, sminolide, pervitide, lixisenatide, dulaglutide, liraglutide, and abiglutide.

7. The method according to any one of the preceding claims, wherein one or more active pharmaceutical ingredients are present in the microparticles of the formulation in an amount between about 1 wt.% and about 40 wt.% of the microparticles.

8. The method according to any one of the preceding claims, wherein one or more active pharmaceutical ingredients are present in the microparticles of the formulation in an amount between about 4 wt.% and about 15 wt.% of the microparticles.

9. The method according to any one of the preceding claims, wherein the pharmaceutical composition comprises a carrier component, wherein the carrier compound is poly(lactic-co-glycolic acid) (PLGA).

10. The method according to any one of the preceding claims, wherein the pharmaceutical composition is administered less than once every 6 months, less than once every 4 months, less than once every 3 months, less than once every 2 months, less than once every 1 month, once every four weeks, or once every two weeks.

11. The method according to any one of the preceding claims, wherein the active pharmaceutical ingredient is encapsulated in biodegradable sustained-release microparticles, wherein the microparticles are in the form of free-flowing powder having an angle of repose of less than about 45 degrees.

12. The method according to any one of the preceding claims, wherein the active pharmaceutical ingredient is encapsulated in biodegradable sustained-release microparticles, wherein the microparticles are in the form of free-flowing powder having an angle of repose of less than about 40 degrees.

13. The method according to any one of the preceding claims, wherein the active pharmaceutical ingredient is encapsulated in biodegradable sustained-release microparticles, wherein the microparticles are in the form of a free-flowing powder having an angle of repose of less than about 35 degrees.

14. The method according to any one of claims 11 to 13, wherein the powder is reconstituted in a physiologically acceptable solvent.

15. The method of claim 14, wherein the powder is redissolved in a non-aqueous phase.

16. The method according to any one of claims 11 to 13, wherein the free-flowing powder is readily dispersed and injected using a static mixing device in a pen syringe.

17. The method according to any one of the preceding claims, wherein the composition is provided in a prefilled syringe, vial, or prefilled syringe.

18. The method of claim 17, wherein the pre-filled syringe is a pen syringe or an auto-injector.

19. The method of claim 17 or 18, wherein the pre-filled syringe is equipped with a 28G-32G needle.

20. The method according to any one of claims 17 to 19, wherein the pre-filled syringe is used for self-administered microsphere formulation.

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