Oral effervescent composition

Abstract

An oral pharmaceutical composition is provided herein that includes a desiccant, a lubricant combination, an effervescent combination, one or more active pharmaceutical ingredient (API), and one or more pharmaceutically acceptable excipient. The present disclosure also provides an oral pharmaceutical composition including a means for controlling moisture content, a means for reducing friction between granules, an effervescent combination, one or more API, and one or more pharmaceutically acceptable excipient. Also provided herein is a method of making an oral pharmaceutical composition by compressing a powder blend, where the powder blend includes a desiccant, a lubricant combination, an effervescent combination, one or more API, and one or more pharmaceutically acceptable excipient.

Description

ORAL EFFERVESCENT COMPOSITIONCROSS-REFERENCE TO RELATED PATENT APPLICATIONS rooon This patent application claims the benefit of U.S. Provisional Application No. 63 / 664,098 filed on June 25, 2024, the entire contents of which is hereby incorporated by reference.FIELD

[0002] This disclosure generally relates to an oral pharmaceutical composition including a desiccant, a lubricant combination, an effervescent combination, one or more active pharmaceutical ingredient (API), and one or more pharmaceutically acceptable excipient, and methods for generating the oral pharmaceutical composition.BACKGROUND

[0003] This section provides background information related to the present disclosure which is not necessarily prior art.

[0004] There are various types of conventional taste-masking techniques, such as adding sweeteners, or flavoring agents to oral pharmaceutical compositions, film coating, freeze-drying, microencapsulation, fluidized bed coating, high shear mixing, and spray drying. However, these conventional methods tend to be cumbersome and require additional processing as well as additional cost. Use of effervescent combinations to taste-mask can be more cost effective and may not result in additional, unpleasant taste perception(s). However, some oral pharmaceutical compositions including an effervescent combination are hard to produce, as the effervescent reaction may activate prematurely due to internal moisture from excipients used in the formulation. Even with a moisture barrier manufactured into the packaging, the effervescent reaction may still occur. Additionally, active pharmaceutical ingredients (APIs) that are highly water soluble are par ticularly difficult to taste mask because they dissolve rapidly in saliva in the oral cavity.

[0005] Despite the commercial availability of oral pharmaceutical compositions including tastemasking agents, there is a need in the art for new and improved compositions.SUMMARY

[0006] This section provides a general summary of the disclosure and is not a comprehensive disclosure of its full scope or all of its features.

[0007] In certain aspects, the present disclosure provides an oral pharmaceutical composition that includes a desiccant, a lubricant combination, an effervescent combination, one or more active pharmaceutical ingredient (API), and one or more pharmaceutically acceptable excipient. In some embodiments, the desiccant may be cyclodextrin or a starch. In some embodiments, the cyclodextrin may be a beta-cyclodextrin. In some embodiments, the lubricant combination may include a metal stearate and stearic acid. In some embodiments, the effervescent combination may include citric acid and sodium bicarbonate. In some embodiments, the API may be a moisture-sensitive API. Additionally or alternatively, the API may be a cough suppressant, an analgesic, an antihistamine, a decongestant, an antacid, an antidiarrheal, an antibiotic, an antiviral, a sedative, or a combination thereof.

[0008] The present disclosure also provides an oral pharmaceutical composition including a means for controlling moisture content, a means for reducing friction between granules, an effervescent combination, one or more API, and one or more pharmaceutically acceptable excipient. In some cases, the oral pharmaceutical composition may be in the form of a tablet.

[0009] In further aspects, the present disclosure provides a method of making an oral pharmaceutical composition as described herein, by compressing a powder blend to form the oral pharmaceutical composition, where the powder blend includes a desiccant, a lubricant combination, an effervescent combination, one or more API, and one or more pharmaceutically acceptable excipient.

[0010] Further areas of applicability will become apparent from the description provided herein. The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The drawings described herein are for illustrative purposes only of selected embodiments and not all possible implementations, and are not intended to limit the scope of the present disclosure.

[0012] FIG. 1 is a bar graph representing main compression force vs tablet hardness and ejection force profile for Formulation 2.

[0013] FIG. 2 is a line graph representing main compression vs tablet hardness profile for Formulation 5.

[0014] FIG. 3 is a line graph representing main compression force vs ejection force profile for Formulation 5.

[0015] FIG. 4 shows the microscopic structure of the different grades of Kleptose® particles (Kleptose® DC, 4% and 7%) and bar graphs representing the water content at equilibrium vs relative humidity (%) of the different Kleptose® grades.

[0016] FIG. 5 is a line graph representing the compression profile (hardness vs compression force) of Kleptose® 200F at different moisture levels (3%, 4%, 5%, 6%, and 8%).

[0017] FIG. 6 is shows FSA levels at shelf life for Kleptose® 200F.DETAILED DESCRIPTIONA. Introduction

[0018] An oral pharmaceutical composition including a desiccant (such as cyclodextrin or a starch), a lubricant combination, an effervescent combination, one or more active pharmaceutical ingredient (API), and one or more pharmaceutically acceptable excipient is disclosed herein. Also disclosed herein are oral pharmaceutical compositions including a means for controlling moisture content, a means for reducing friction between granules, an effervescent combination, one or more API, and one or more pharmaceutically acceptable excipient.

[0019] Although cyclodextrin is not a common ingredient used to produce tablets, the inventors have found that using cyclodextrin in oral pharmaceutical compositions can help to control moisture content. Thus, a tablet for delivering APIs, such as water-soluble APIs, to the oral cavity, may be generated, by using a formulation of excipients, such as a desiccant, a lubricant combination, an effervescent combination, and a pharmaceutically acceptable excipient. The lubricant combination, when combined with other components, allows tablets to be formed with a desired tablet hardness and ejection force, which are important for tablet manufacturability, while the effervescent reaction can be prevented from occurring prematurely (i.e., before contacting an outside source of moisture, such as saliva).

[0020] A method of making an oral pharmaceutical composition as described herein by compressing a powder blend including the described ingredients is also disclosed.

[0021] Example embodiments are provided so that this disclosure will be thorough and will fully convey the scope to those who are skilled in the art. Numerous specific details are set forth such as examples of specific compositions and methods, to provide a thorough understanding of embodiments of the present disclosure. It will be apparent to those skilled in the art that specific details need not be employed, that example embodiments may be embodied in many different forms and that neither should be construed to limit the scope of the disclosure. In some example embodiments, well-known processes, well-known device structures, and well-known technologies are not described in detail.B. Definitions

[0022] The terminology used herein is for the purpose of describing particular example embodiments only and is not intended to be limiting. As used herein, the singular forms “a,” “an,” and “the” may be intended to include the plural forms as well, unless the context clearly indicates otherwise. The terms “comprises,” “comprising,” “including,” and “having,” are inclusive and therefore specify the presence of stated features, elements, compositions, steps, integers, operations, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof. Although the open-ended term “comprising,” is to be understood as a non-restrictive term used to describe and claim various embodiments set forth herein, in certain aspects, the term may alternatively be understood to instead be a more limiting and restrictive term, such as “consisting of’ or “consisting essentially of.” Thus, for any given embodiment reciting compositions, materials, components, elements, features, integers, operations, and / or process steps, the present disclosure also specifically includes embodiments consisting of, or consisting essentially of, such recited compositions, materials, components, elements, features, integers, operations, and / or process steps. In the case of “consisting of,” the alternative embodiment excludes any additional compositions, materials, components, elements, features, integers, operations, and / or process steps, while in the case of “consisting essentially of,” any additional compositions, materials, components, elements, features, integers, operations, and / or process steps that materially affect the basic and novel characteristics are excluded from such an embodiment, but any compositions, materials, components, elements, features, integers, operations, and / or process steps that do not materially affect the basic and novel characteristics can be included in the embodiment.

[0023] Any method steps, processes, and operations described herein are not to be construed as necessarily requiring their performance in the particular order discussed or illustrated, unlessspecifically identified as an order of performance. It is also to be understood that additional or alternative steps may be employed, unless otherwise indicated.

[0024] The use of the term "a" or "an" when used in conjunction with the term "comprising" in the claims and / or the specification may mean "one," but it is also consistent with the meaning of "one or more," "at least one," and "one or more than one." As such, the terms "a," "an," and "the" include plural referents unless the context clearly indicates otherwise. Thus, for example, reference to "a compound" may refer to one or more compounds, two or more compounds, three or more compounds, four or more compounds, or greater numbers of compounds.

[0025] The use of the term "at least one" will be understood to include one as well as any quantity more than one, including but not limited to, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, etc. The term "at least one" may extend up to 100 or 1000 or more, depending on the term to which it is attached; in addition, the quantities of 100 / 1000 are not to be considered limiting, as higher limits may also produce satisfactory results. In addition, the use of the term "at least one of X, Y, and Z" will be understood to include X alone, Y alone, and Z alone, as well as any combination of X, Y, and Z. The use of ordinal number terminology (i.e., "first," "second," "third," "fourth," etc.) is solely for the purpose of differentiating between two or more items and is not meant to imply any sequence or order or importance to one item over another or any order of addition, for example.

[0026] The use of the term "or" in the claims is used to mean an inclusive "and / or" unless explicitly indicated to refer to alternatives only or unless the alternatives are mutually exclusive. For example, a condition "A or B" is satisfied by any of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).

[0027] As used herein, any reference to "one embodiment," "an embodiment," "some embodiments," "one example," "for example," or "an example" means that a particular element, feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. The appearance of the phrase "in some embodiments" or "one example" in various places in the specification is not necessarily all referring to the same embodiment, for example. Further, all references to one or more embodiments or examples are to be construed as non-limiting to the claims.

[0028] Throughout this disclosure, the term "about" is used to indicate that a value includes the inherent variation of error for a composition / apparatus / device, the method being employed to determine the value, or the variation that exists among the study subjects. For example, but not by wayof limitation, when the term "about" is utilized, the designated value may vary by plus or minus twenty percent, or fifteen percent, or twelve percent, or eleven percent, or ten percent, or nine percent, or eight percent, or seven percent, or six percent, or five percent, or four percent, or three percent, or two percent, or one percent from the specified value, as such variations are appropriate to perform the disclosed methods and as understood by persons having ordinary skill in the art. Particularly in reference to a given quantity, number or percentage, “about” is meant to encompass deviations of plus or minus ten percent (± 10). For example, about 5% encompasses any value between 4.5% to 5.5%, such as 4.5, 4.6, 4.7, 4.8, 4.9, 5, 4.1, 5.2, 5.3, 5.4, or 5.5. Accordingly, unless otherwise indicated, the numerical parameters set forth in this specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by the presently disclosed subject matter.

[0029] The term "or combinations thereof" as used herein refers to all permutations and combinations of the listed items preceding the term. For example, "A, B, C, or combinations thereof" is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AAB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context.

[0030] As will be understood by one skilled in the art, for any and all purpose, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Furthermore, as will be understood by one skilled in the art, a range includes each individual member.

[0031] Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the ait. In particular, this disclosure utilizes routine techniques in the field of effervescent combinations and tablet moisture control.

[0032] The term “active pharmaceutical ingredient” or “API” as used herein refers to any molecule, composition, formulation, compound, ingredient, or substance that is an active component in a pharmaceutical drug that prevents, diagnoses, treats, or cures disease or disease symptoms in a mammal, such as a human or non-human mammal, such as domesticated animals (dogs, cats, etc.) and farm animals (cows, horses, pigs, etc.). APIs may be “over-the-counter” and not require a drug prescription, while some may require a drug prescription from a medically-authorized person.C. Compositions

[0033] In some embodiments, an oral pharmaceutical composition including a desiccant, a lubricant combination, an effervescent combination, one or more active pharmaceutical ingredient (API), and one or more pharmaceutically acceptable excipient is provided herein. In some embodiments, an oral pharmaceutical composition including a means for controlling moisture content, a means for reducing friction between granules, an effervescent combination, one or more active pharmaceutical ingredient, and one or more pharmaceutically acceptable excipient is provided herein.Desiccant

[0034] As described above, a desiccant may be included in the oral pharmaceutical composition provided herein to control moisture content and granulation size. Thus, in some embodiments, desiccants may be used to induce and / or sustain a state of dryness. In some embodiments, a pharmaceutical composition comprises about 15-60, about 25-50 or about 30-40 wt. % desiccant. In some embodiments, a pharmaceutical composition comprises less than or equal to about 60, about 55, about 50, about 45, about 40, about 35, about 30, about 25, about 20, or about 15 wt. % desiccant. In some embodiments, a pharmaceutical composition comprises greater than or equal to about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, or about 55 wt. % desiccant. In certain embodiments, a pharmaceutical composition comprises about 20 wt. % desiccant. In certain embodiments, a pharmaceutical composition comprises about 20 wt. % Kleptose®. In certain embodiments, a pharmaceutical composition comprises about 15 wt. % Kleptose®.

[0035] In some embodiments, the desiccant may be a cyclodextrin, a starch, a magnesium aluminosilicate (i.e., aluminum-magnesium silicate), or a combination thereof. In some embodiments, the starch may be Starch 1500® or Starch 3 % (a 3% starch solution). In some embodiments, the magnesium aluminosilicate may be magnesium aluminosilicate, magnesium aluminum silicate, magnesium aluminate metasilicate, aluminum magnesium silicate, Veegum®, or Almasilate. In some embodiments, the magnesium aluminosilicate may be Neusilin® US2. In some embodiments, the cyclodextrin may be an alpha-cyclodextrin, beta-cyclodextrin, gammacyclodextrin, or a combination thereof. As referred to herein, a cyclodextrin may include any cyclodextrin derivatives. In some cases, the cyclodextrin may be modified via methylation, acetylation, etc. In some embodiments, the cyclodextrin may be a beta-cyclodextrin (e.g., Kleptose®). In some embodiments, the cyclodextrin may be a methyl-beta-cyclodextrin. In some embodiments, the cyclodextrin may be crystalline. Additionally or alternatively, in someembodiments, the cyclodextrin may be partially amorphous. In some embodiments, amorphous cyclodextrin may adsorb moisture more readily and to a higher extent compared to crystalline cyclodextrin. Thus, in some embodiments, the desiccant may comprise cyclodextrin, Starch 1500®, Starch 3 %, Kleptose 20%, Neusilin® US2, or a combination thereof.

[0036] In some embodiments, moisture content may alter tablet compressibility potential and tablet hardness. In some embodiments, higher moisture content may result in harder tablets. In some embodiments, the desiccant may have a moisture content of about 3% to about 10%, about 3.5% to about 9.5%, about 4.0% to about 9.0%, about 4.5% to about 8.5%, about 5% to about 8%, about 5.5% to about 7.5%, or about 6% to about 7%. In certain embodiments, the desiccant may have a moisture content of about 5.0% to about 7.0%. Moisture content may be calculated by methods known in the art, such as via the following formula: MC=(w-d) / w*100, where MC is the moisture content (%), w is the weight while wet, and d is the weight while dry. In some embodiments, to determine moisture content, methods known in the art, such as Loss on Drying (LOD) and water quantification via Karl Fisher (KF) titration, may be used. LOD measures the loss of weight of a sample when heated to 105°C for a set time. KF is based on a reaction in which the water in the sample reacts with a reagent.

[0037] In some embodiments, smaller desiccant particle size may yield higher tablet hardness. In some embodiments, the desiccant may have a particle size distribution (PSD) of about 1 pm to about 1,000 pm, 20 pm to about 1,000 pm, 40 pm to about 1,000 pm, about 50 pm to about 1,000 pm, about 60 pm to about 1,000 pm, about 70 pm to about 1,000 pm, about 80 pm to about 1,000 pm, about 90 pm to about 1,000 pm, about 100 pm to about 1,000 pm, about 150 pm to about 1,000 pm, about 200 pm to about 1,000 pm, about 250 pm to about 1,000 pm, about 300 pm to about 1,000 pm, about 350 pm to about 1,000 pm, about 400 pm to about 1,000 pm, about 450 pm to about 1,000 pm, about 500 pm to about 1,000 pm, about 550 pm to about 1,000 pm, about 600 pm to about 1,000 pm, about 650 pm to about 1,000 pm, about 700 pm to about 1,000 pm, about 750 pm to about 1,000 pm, about 800 pm to about 1,000 pm, about 850 pm to about 1,000 pm, about 900 pm to about 1,000 pm, about 950 pm to about 1,000 pm, about 40 pm to about 950 pm, about 40 pm to about 900 pm, about 40 pm to about 850 pm, about 40 pm to about 800 pm, about 40 pm to about 750 pm, about 40 pm to about 700 pm, about 40 pm to about 650 pm, about 40 pm to about 600 pm, about 40 pm to about 550 pm, about 40 pm to about 500 pm, about 40 pm to about 450 pm, about 40 pm to about 400 pm, about 40 pm to about 350 pm, about 40 pm to about 300 pm, about 40 pm to about 250 pm, about 40 pm to about 200 pm, about 40 pm to about 150 pm, about 40 pm to about 100 pm, about 40 pm to about 90 pm, about 40 pm to about 80 pm, about 40 pm to about 70 pm, about 40 pm to about 60 pm, about40 pm to about 50 pm, about 100 to about 900 pm, about 150 to about 850 pm, about 200 pm to about 800 pm, about 250 pm to about 750 pm, about 300 pm to about 700 pm, about 350 pm to about 650 pm, about 400 pm to about 600 pm, about 450 pm to about 550 pm, or about 475 pm to about 525 pm. In certain embodiments, the cyclodextrin may have a PSD of about 40 pm to about 1,000 pm. PSD may be calculated by known methods known in the art, such as sieve analysis, air elutriation analysis, photoanalysis, optical counting methods, electroresistance counting methods, sedimentation techniques, laser diffraction methods, or Laser Obscuration Time" (LOT) or "Time Of Transition" (TOT).

[0038] In some embodiments, the desiccant may be present in the oral pharmaceutical composition at about 0.1%, about 1.0%, about 5.0%, about 10.0%, about 15.0%, about 16.0%, about 17.0%, about 18.0%, about 19.0%, about 20.0%, about 21.0%, about 22.0%, about 23.0%, about 24.0%, about 25.0%, about 30.0%, about 35.0%, about 40.0%, about 45.0%, about 50.0%, about 0.1% to about 50.0%, about 1.0% to about 45.0%, about 5.0% to about 40.0%, about 10.0% to about 35.0%, about 15.0% to about 30.0%, about 20.0% to about 25.0%, about 0.1% to about 45.0%, about 0.1% to about 40.0%, about 0.1% to about 35.0%, about 0.1% to about 30.0%, about 0.1% to about 25.0%, about 0.1% to about 20.0%, about 0.1% to about 15.0%, about 0.1% to about 10.0%, about 0.1% to about 5.0%, about 0.1% to about 1.0%, about 1.0% to about 50.0%, about 5% to about 50.0%, 10% to about 50.0%, about 15% to about 50.0%, about 20% to about 50.0%, about 25% to about 50.0%, about 30% to about 50.0%, about 35% to about 50.0%, about 40% to about 50.0%, or about 45% to about 50.0% desiccant, by weight of the oral pharmaceutical composition. In certain embodiments, the desiccant may be present in the oral pharmaceutical composition at about 21.0% desiccant, by weight of the oral pharmaceutical composition.Lubricant combination

[0039] In some embodiments, the oral pharmaceutical composition includes a lubricant combination containing metal stearate and stearic acid. In some embodiments, the metal stearate may be magnesium stearate, calcium stearate, zinc stearate, aluminum stearate, barium stearate, lithium stearate, or a combination thereof. In a specific embodiment, the lubricant combination includes magnesium stearate and stearic acid. In some embodiments, the oral pharmaceutical composition may include about 0.05% to about 5.0%, about 0.1% to about 5%, about 0.2% to about 5%, about 0.3% to about 5%, about 0.4% to about 5%, about 0.5% to about 5%, about 0.6% to about 5%, about 0.7% to about 5%, about 0.8% to about 5%, about 0.9% to about 5%, about 1.0% to about 5%, about 1.5% to about 5%, about 2% to about 5%, about 2.5% to about 5%, about 3% to about 5%, about 3.5% to about5%, about 4% to about 5%, about 4.5% to about 5%, about 0.05% to about 4.5%, about 0.05% to about 4%, about 0.05% to about 3.5%, about 0.05% to about 3%, about 0.05% to about 2.5%, about 0.05% to about 2%, about 0.05% to about 1.5%, or about 0.05% to about 1% magnesium stearate, by weight of the composition. In a certain embodiment, the oral pharmaceutical composition may include about 0.5% magnesium stearate, by weight of the composition. In some embodiments, the oral pharmaceutical composition may include about 1% to about 10.0%, about 2% to about 9%, about 3% to about 8%, about 4% to about 7%, about 5% to about 6%, about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1 % to about 3%, about 1 % to about 2%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, or about 9% to about 10% stearic acid, by weight of the composition. In a certain embodiment, the oral pharmaceutical composition may include about 2.0% stearic acid, by weight of the composition.

[0040] In some embodiments, the lubricant combination, or one of the components in the lubricant combination, may reduce friction between the oral pharmaceutical composition particles and the tablet press during the oral pharmaceutical composition tablet compression process. Thus, in some embodiments, the lubricant combination, or one of the components in the lubricant combination, may help facilitate the ejection of the compressed tablet from the tablet punch cavity, preventing sticking. In some embodiments, the lubricant combination, or one of the components in the lubricant combination, may be present in the oral pharmaceutical composition at about 0.25% to about 5% w / w, about 0.5% to about 4%, about 1% to about 3.5%, about 1.5% to about 3%, about 2% to about 2.5%, about 0.25%, about 0.5%, about 0.75%, about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20%. In certain embodiments, the lubricant combination may be present in the oral pharmaceutical combination at about 2.5%.

[0041] In some embodiments, instead of metal stearate, calcium palmitate, magnesium palmitate, palmitic acid, or a combination thereof could be used. In some embodiments, the oral pharmaceutical composition may further include calcium palmitate, magnesium palmitate, palmitic acid, or a combination thereof in addition to metal stearate.

[0042] Additional lubricants such as external lubrication, applied to the outside of the tablet, and / or punch coatings may also be included in some embodiments. In some embodiments, theexternal lubricant may be zinc stearate or magnesium stearate. In some embodiments, the external lubricant may be mixed with sodium carbonate or another carrier.Effervescent combination

[0043] An effervescent combination refers to any combination of ingredients / components that produce carbon dioxide in a liquid and may mask a perceived unpleasant taste of a molecule or composition. Non-limiting examples of perceived unpleasant tastes include bitter, sour, pungent, astringent, cardboardy, dusty, dry, floury, rancid, and metallic tastes and / or aftertastes. In some embodiments, the effervescent combination comprises sodium bicarbonate and citric acid. The effervescent combination may further comprise an additional component besides sodium bicarbonate and citric acid to help taste mask the molecule or composition. Additional taste masking components include sweetening agents, flavoring agents, or flavor-blocking agents, such as bitter flavor blockers. Bitter flavor blockers may include adenosine monophosphate, lipoproteins, or phospholipids, and may compete with the bitter molecules / compositions to bind to the G-protein coupled receptors on the tongue (receptor sites that detect bitterness), thus suppressing the bitter taste.

[0044] Thus, the effervescent combination may be referred to as a combination (including two, three, four, five, etc. components). When the effervescent combination only includes two components, it may be referred to as an effervescent couple.Molar ratio of sodium bicarbonate to citric acid

[0045] Sodium bicarbonate, CAS Number 144-55-8, is a chemical compound having the IUPAC name sodium hydrogen carbonate and chemical formula Nal ICO3. It is a salt composed of a sodium cation (Na+) and a bicarbonate anion (HCCh-). It is commonly known as baking soda. Sodium bicarbonate or calcinated sodium bicarbonate (heated sodium bicarbonate to remove moisture making it more anhydrous) may be used herein.

[0046] Citric acid, CAS Number 77-92-9, is an organic compound having the IUPAC name 2- hydroxypropane- 1 ,2,3-tricarboxylic acid and chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid and has two forms. Citric acid can be obtained as an anhydrous (water- free) form or as a monohydrate. In one embodiment, citric acid as used herein is citric acid, anhydrous (containing less than 1% water).

[0047] In one embodiment, the effervescent combination may be present at a particular molar ratio of sodium bicarbonate to citric acid. The molar ratio of sodium bicarbonate to citric acid may allowthe effervescent combination to reduce bitterness perception via increased electric potential / degree of carbonation.

[0048] In some embodiments, the effervescent combination may be present in a molar ratio of about 2:1 to about 3:1 moles of sodium bicarbonate to citric acid. Thus, in some embodiments, the effervescent combination may mask the bitter taste perception of inorganic and organic molecules and compositions, such as APIs and compositions comprising APIs.

[0049] As used herein about 2 moles of sodium bicarbonate may refer to a range of about 1.5 to2.5 moles, 1.6 to 2.5 moles, 1.7 to 2.5 moles, 1.8 to 2.5 moles, 1.9 to 2.5 moles, 2.0 to 2.5 moles, 2.1 to 2.5 moles, 2.2 to 2.5 moles, 2.3 to 2.5 moles, 2.4 to 2.5 moles, 1.5 to 2.4 moles, 1.5 to 2.3 moles,1.5 to 2.2 moles, 1.5 to 2.1 moles, 1.5 to 2.0 moles, 1.5 to 1.9 moles, 1.5 to 1.8 moles, 1.5 to 1.7 moles,1.5 to 1.6 moles, 1.6 to 2.4 moles, 1.7 to 2.3 moles, 1.8 to 2.2 moles, 1.9 to 2.1 moles, 1.8 to 2.0 moles, or 1.95 to 2.05 moles. For example about 2 moles of sodium bicarbonate may be about 1.5, 1.55, 1.6,1.65, 1.7, 1.75, 1.8, 1.85, 1.9, 1.95, 2.0, 2.05, 2.1, 2.15, 2.2, 2.25, 2.3, 2.35, 2.4, 2.45, or 2.5 moles of sodium bicarbonate.

[0050] As used herein about 3 moles of sodium bicarbonate may refer to a range of about 2.5 to3.5 moles, 2.6 to 3.5 moles, 2.7 to 3.5 moles, 2.8 to 3.5 moles, 2.9 to 3.5 moles, 3.0 to 3.5 moles, 3.1 to 3.5 moles, 3.2 to 3.5 moles, 3.3 to 3.5 moles, 3.4 to 3.5 moles, 2.5 to 3.4 moles, 2.5 to 3.3 moles,2.5 to 3.2 moles, 2.5 to 3.1 moles, 2.5 to 3.0 moles, 2.5 to 2.9 moles, 2.5 to 2.8 moles, 2.5 to 2.7 moles,2.5 to 2.6 moles, 2.6 to 3.4 moles, 2.7 to 3.3 moles, 2.8 to 3.2 moles, 2.9 to 3.1 moles, 2.8 to 3.0 moles, or 2.95 to 3.05 moles. For example about 3 moles of sodium bicarbonate may be about 2.5, 2.55, 2.6,2.65, 2.7, 2.75, 2.8, 2.85, 2.9, 2.95, 3.0, 3.05, 3.1, 3.15, 3.2, 3.25, 3.3, 3.35, 3.4, 3.45, or 3.5 moles of sodium bicarbonate.

[0051] As used herein, about 1 mole of citric acid may refer to a range of 0.5 to 1.5 moles, 0.6 to1.5 moles, 0.7 to 1.5 moles, 0.8 to 1.5 moles, 0.9 to 1.5 moles, 1.0 to 1.5 moles, 1.1 to 1.5 moles, 1.2 to 1.5 moles, 1.3 to 1.5 moles, 1.4 to 1.5 moles, 0.5 to 1.4 moles, 0.5 to 1.3 moles, 0.5 to 1.2 moles, 0.5 to 1.1 moles, 0.5 to 1.0 moles, 0.5 to 0.9 moles, 0.5 to 0.8 moles, 0.5 to 0.7 moles, 0.5 to 0.6 moles, 0.6 to 1.4 moles, 0.7 to 1.3 moles, 0.8 to 1.2 moles, 0.9 to 1.1 moles, 0.8 to 1.0 moles, or 0.95 to 1.05 moles of citric acid. For example, about 1 mole of citric acid may be 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 0.96, 0.97, 0.98, 0.99, 1.0, 1.1, 1.2, 1.3, 1.4, or 1.5 moles of citric acid.

[0052] Each range disclosed herein includes end values. Additionally, each value disclosed herein can be part of a range with another disclosed value. Ultimately, one skilled in the art is aware that minor variations in the ratio of 3:1 can be used and still provide taste masking benefits.

[0053] For purposes of this disclosure, the molecular weight used for citric acid is 192.12 g / mol and the molecular weight for sodium bicarbonate is 84.01 g / mol. Additionally, for purposes of this disclosure, the amount of moles of a compound is calculated by dividing the grams of a compound by the molecular weight of that compound.

[0054] For example, the following calculation is used to determine the moles of citric acid (CA) in 0.25 grams of CA:,25g CA 1 mole CA- ,25g / 192.12g = 0.001301 mol CA1 192.12g CA

[0055] Additionally, for example, the following calculation is used to determine the moles of sodium bicarbonate (SB) in 0.25 grams of SB:1 mole SB= ,25g / 84.01g = .002976 mol SB84.01g SB

[0056] In some embodiments, the number of moles can be brought out to 4 significant figures.

[0057] Thus, the molar ratio of SB:CA in this example is .002976:0.001301. Molar ratio may be simplified to the “n:l” form. For example, the following calculation may be used to determine the molar ratio in “n:l” form:.002976 x- = — ; x = 2.2873 ; thus the SB: CA molar ratio is 2.2873: 1.001301 1Amount of effervescent combination in oral pharmaceutical composition

[0058] Further, the effervescent combination may be present in the oral pharmaceutical composition in any amount sufficient to reduce the perception and / or impression of bitterness of one or more bitter tasting molecule or composition, such as an API or a composition comprising an API.

[0059] For example, in one embodiment, the effervescent combination may be present in the oral pharmaceutical composition in an amount of about 0.1% to about 40%, about 0.1% to about 35%, 0.1% to about 30%, about 1% to about 29%, about 2% to about 28%, about 3% to about 27%, about 4% to about 26%, about 5% to about 25%, about 6% to about 24%, about 7% to about 23%, about 8% to about 22%, about 9% to about 21%, about 10% to about 20%, about 11% to about 19%, about 12% to about 18%, about 13% to about 17%, about 14% to about 16%, about 1% to about 20%, about 2% to about 20%, about 3% to about 20%, about 4% to about 20%, about 5% to about 20%, about 6% to about 20%, about 7% to about 20%, about 8% to about 20%, about 9% to about 20%, about 10% to about 20%, about 11% to about 20% about 12% to about 20%, about 13% to about 20%, about 14% to about 20%, about 15% to about 20%, about 16% to about 20%, about 17% to about 20%, about 18% to about 20%, about 19% to about 20%, about 1% to about 19%, about 1% to about 18%, about 1% to about 17%, about 1% to about 16%, about 1% to about 15%, about 1% to about 14%, about 1% to about 13%, about 1% to about 12%, about 1% to about 11%, about 1% to about 10%, about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1% to about 3%, about 1% to about 2%, about 1% to about 10%, about 10% to about 20%, about 20% to about 30%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 10.5%, about 11%, about 11.5%, about 12%, about 12.5%, about 13%, about 13.5%, about 14%, about 14.5%, about 15%, about 15.5%, about 16%, about 16.5%, about 17%, about 17.5%, about 18%, about 18.5%, about 19%, about 19.5%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, or about 40% weight by weight (%w / w) of the oral pharmaceutical composition. In a particular embodiment, the effervescent combination may be present in the oral pharmaceutical composition in an amount of about 13% w / w of the oral pharmaceutical composition. In a further particular embodiment, the sodium bicarbonate and citric acid are present in a weight ratio of about 1:2 in the oral pharmaceutical composition. For example, about 50 mg: 100 mg sodium bicarbonate to citric acid.

[0060] In another particular embodiment, sodium bicarbonate and citric acid may each be present in the oral pharmaceutical composition in an amount from about 25 to about 600, about 25 to about 550, about 25 to about 500, about 25 to about 450, about 25 mg to about 400 mg, 50 mg to about 350 mg, 75 mg to about 300 mg, 100 mg to about 300 mg, about 125 mg to about 300 mg, about 150 mg to about 250 mg. In certain embodiments, sodium bicarbonate and citric acid may each be present in the same or different amounts, such as about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, about 200 mg, about 205 mg, about 210 mg, about 215 mg, about 220 mg, about225 mg, about 230 mg, about 235 mg, about 240 mg, about 245 mg, about 250 mg, about 255 mg, about 260 mg, about 265 mg, about 270 mg, about 275 mg, about 280 mg, about 285 mg, about 290 mg, about 295 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about550 mg, or about 600 mg per tablet. In a further particular’ embodiment, the sodium bicarbonate and citric acid are present in substantially the same weight amount in the oral pharmaceutical composition. For example, about 150 mg: 150 mg sodium bicarbonate to citric acid or about 200 mg:200 mg sodium bicarbonate to citric acid or about 250 mg:250 mg sodium bicarbonate to citric acid.

[0061] Similarly, each ingredient / component in the effervescent combination (sodium bicarbonate, citric acid, etc.) may be present in the oral pharmaceutical composition in an amount of about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 1% to about 50%, about 5% to about 45%, about 10% to about 40%, and about 20% to about 40% weight by weight (%w / w) of the oral pharmaceutical composition.Active pharmaceutical ingredient (API)

[0062] Additionally, the oral pharmaceutical composition contains at least one API. In other embodiments, the disclosed compositions may not include an API (e.g., a placebo).

[0063] In some embodiments, an API may have an unpleasant taste perception, such as a perceived bitter taste, bland taste, earthy taste, or other undesirable taste. The effervescent combination described herein may be used to mask the taste of any API, for example, by raising the electric potential of the molecule or composition when dissolved in water.

[0064] In some embodiments, the API may be a moisture- sensitive API. A non-limiting list of moisture-sensitive APIs includes, but is not limited to aspirin, acyclovir, erythromycin base, itraconazole, and ketoconazole.

[0065] Non-limiting examples of APIs include inorganic molecules such as acids, oxo acids, hydroxides, metal oxides, non-metal oxides, binary salts and those containing polyatomic ions, peroxides, aragonite, potassium, phosphorous, calcium, magnesium, sulfur, sodium chloride, calcium chloride, potassium chloride, sodium sulfate, calcium phosphate, calcium carbonate, zinc sulfate, and magnesium chloride, organic molecules such as nucleic acids, lipids, sugars, proteins, enzymes, hydrocarbon fuels, carbohydrates, solvents, drugs, vitamins, dyes, artificial flavors, toxins, molecules used as precursors to biochemical compounds, loratadine (commonly referred to as Claritin®), desloratadine (commonly referred to as Clarinex®, etc.), azelastine (commonly referred to as Astelin®, Astepro®, Optivar®, etc.), dextromethorphan hydrobromide (commonly referred to as Dex. HBr, Benylin®, Delsym®, etc.), naproxen sodium (commonly referred to as Aleve®, Anaprox®, Naprosyn®, etc.), diphenhydramine hydrochloride (commonly referred to as Benadryl®, Banophen™, etc.), acetaminophen (commonly referred to as Tylenol®, etc.), guaifenesin (commonly referred to as Guiatuss®, Robitussin®, etc.), chlorpheniramine (commonly referred to as Chlor- Trimeton®, Piriton™, etc.), phenylephrine (commonly rcl'crrcd to as Neo-synephrine®, etc.), pseudoephedrine (commonly referred to as Afrinol, Sudafed®, etc.), doxylamine (commonly referred to as Unisom®, Vicks®, etc.), acetylsalicylic acid (commonly referred to as Aspirin, etc.), mometasone (commonly referred to as Elocon®, etc.), caffeine, acetaldehyde, acetone, biotin, heptane, vanillin, methanol, bromophenol blue, carbon tetrachloride, fullerene, and benzaldehyde. The organic molecule may be natural or synthetic. In some embodiments, the API may include one or more vitamins. In a certain embodiment, the API may include vitamin C. In some embodiments, the API may include a vitamin premix. In a particular embodiment, the API may be dextromethorphan HBr (Dex. HBr). In a particular embodiment, the one or more API may include dextromethorphan HBr, benzonatate, codeine, pholcodine, or a combination thereof.

[0066] In some embodiments, the API can be from a therapeutic class of drugs, such as cough suppressants, antihistamines, decongestants, antacids, antidiarrheals, analgesics, antibiotics, antivirals, sedatives, and stimulants.

[0067] In some embodiments, the one or more API may be an analgesic, such as acetaminophen (APAP); a COX-2 inhibitor; opioid; alcohol; cannabis; a nonsteroidal anti-inflammatory drug (NSAID), such as aspirin, ibuprofen, and naproxen; or a combination thereof.

[0068] In some embodiments, the one or more API may be an antihistamine, such as an Hl- antihistamine (e.g., Azelastine, Chlorphenamine (CPM), Hydroxyzine, Loratadine, and Trazodone); an H2-antihistamine (e.g., Cimetidine and Ranitidine; H3-antihistamines, such as Clobenpropit andConessine); an H4-antihistamine (e.g., Thioperamide); a histidine decarboxylase inhibitor (e.g., Tritoqualine); a mast cell stabilizer (e.g., Nedocromil); or a combination thereof.

[0069] In some embodiments, the one or more API may include a combination comprising a cough suppressant, analgesic, an antihistamine, or a combination thereof.

[0070] In some embodiments, the one or more API may include antihistamine, antitussive, bronchodilator, expectorant, or nasal decongestant active ingredients, or a combination thereof. Such active ingredients are available in 21 CFR Part 341 Subpart B (www.ecfr.gov / current / title-21 / chapter- I / subchapter-D / part-341 / subpart-B ) .

[0071] In some embodiments, the one or more API may include antihistamine active ingredients, such as brompheniramine maleate, chlorcyclizine hydrochloride, chlorpheniramine maleate, dexbrompheniramine maleate, dexchlorpheniramine maleate, diphenhydramine citrate, diphenhydramine hydrochloride, doxylamine succinate, phenindamine tartrate, pheniramine maleate, pyrilamine maleate, thonzylamine hydrochloride, triprolidine hydrochloride, or a combination thereof.

[0072] In some embodiments, the one or more API may include antitussive active ingredients, such as oral antitussives (e.g., chlophedianol hydrochloride); codeine ingredients (e.g., codeine, codeine phosphate, codeine sulfate, dextromethorphan, dextromethorphan hydrobromide, diphenhydramine citrate, diphenhydramine hydrochloride); topical antitussives (e.g., camphor, menthol); or a combination thereof.

[0073] In some embodiments, the one or more API may include bronchodilator active ingredients, such as ephedrine, ephedrine hydrochloride, ephedrine sulfate, epinephrine, epinephrine bitartrate, racephedrine hydrochloride, racepinephrine hydrochloride, or a combination thereof.

[0074] In some embodiments, the one or more API may include expectorant active ingredients, such as guaifenesin.

[0075] In some embodiments, the one or more API may include nasal decongestant active ingredients, such as oral nasal decongestants (e.g., phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, phenylephrine bitartrate in an effervescent dosage form); topical nasal decongestants (e.g., levmetamfetamine, ephedrine, ephedrine hydrochloride, ephedrine sulfate, naphazoline hydrochloride, oxymetazoline hydrochloride, phenylephrine hydrochloride, propylhexedrine, xylometazoline hydrochloride); or a combination thereof.

[0076] In some embodiments, the API may be Acetaminophen (e.g., Acetaminophen Microcaps (APAP)), Chlorpheniramine Maleate, Dextromethorphan HBr (Dex. HBr), Doxylamine Succinate, Chlorpheniramine Maleate, Pseudoephedrine Hydrochloride, aspirin (e.g., Aspirin 180 / 840), or a combination thereof. In certain embodiments, the API may include Acetaminophen (e.g., Acetaminophen Microcaps (APAP)), Chlorpheniramine Maleate, and Dextromethorphan HBr (Dex. HBr). In certain embodiments, the API may include Acetaminophen (e.g., Acetaminophen Microcaps (APAP)), Doxylamine Succinate, and Dextromethorphan HBr (Dex. HBr). In certain embodiments, the API may include Acetaminophen (e.g., Acetaminophen Microcaps (APAP)), Chlorpheniramine Maleate, and Dextromethorphan HBr (Dex. HBr). In certain embodiments, the API may include Acetaminophen (e.g., Acetaminophen Microcaps (APAP)) and Chlorpheniramine Maleate. In certain embodiments, the API may include Acetaminophen (e.g., Acetaminophen Microcaps (APAP)), Chlorpheniramine Maleate, Dextromethorphan HBr (Dex. HBr), and Pseudoephedrine Hydrochloride. In certain embodiments, the API may include aspirin (e.g., Aspirin 180 / 840). In some embodiments, the API may be Acetaminophen (e.g., Acetaminophen Microcaps (APAP)).

[0077] Each API may be present in the oral pharmaceutical composition in an amount of about 1% to about 10%, 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to about 80%, about 80% to about 90%, about 90% to about 100%, about 1% to about 50%, about 50% to about 100%, about 5% to about 45%, about 10% to about 40%, about 20% to about 40%, about 55% to about 95%, about 60% to about 90%, or about 70% to about 80% weight by weight (%w / w) of the oral pharmaceutical composition. The API may be present in an amount of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, or about 95%w / w. In a particular embodiment, the API may be present in an amount of about 70.5 %w / w. In a particular embodiment, the oral pharmaceutical composition may include about 0.05 wt. % to about 35% of the one or more API, by weight of the composition.

[0078] In some embodiments, the molar ratio of desiccant to one or more API in the oral pharmaceutical composition may be about 3:1 to about 25:1, about 4:1 to about 24:1, about 5:1 to about 23:1, about 6:1 to about 22:1, about 7:1 to about 21:17, about 10:1 to about 20:1, about 11:1 to about 19:1, about 12:1 to about 18:1, about 13:1 to about 17:1, about 14:1 to about 16:1. In some embodiments, the molar ratio of desiccant to one or more API may be less than or equal to about 25: 1, about 24:1, about 23:1, about 22:1, about 21:1, about 20:1, about 19:1, about 18:1, or about 17:1. Insome embodiments, the molar ratio of desiccant to one or more API may be greater than or equal to about 3:1, about 4:1, about 5:1, about 6:1, about 7:1, about 10:1, about 11:1, about 12:1, or about 13:1. In a particular embodiment, the molar ratio of desiccant to one or more API may be about 17:1. Molar ratio may be calculated similar to the molar ratio calculations for the effervescent combination as described herein.

[0079] Each API may be present in the oral pharmaceutical composition in an amount of about 1 mg to about 700 mg, about 5 mg to about 700 mg, about 10 mg to about 700mg, about 15 mg to about 700 mg, about 20 mg to about 700 g, about 1 mg to about 100 mg, about 5 mg to about 50 mg, about 10 mg to about 25 mg, about 15 mg to about 20 mg, about 1 mg to about 10 mg, about 2 mg to about 9 mg, about 3 mg to about 8 mg, about 4 mg to about 7 mg, about 5 mg to about 6 mg, about 25 to about 700, about 25 to about 650, about 25 to about 600, about 25 to about 550, about 25 to about 500, about 25 to about 450, about 25 mg to about 400 mg, 50 mg to about 350 mg, 75 mg to about 300 mg, 100 mg to about 300 mg, about 125 mg to about 300 mg, about 150 mg to about 250 mg. In certain embodiments, each API may each be present in the same or different amounts, such as about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, about 200 mg, about 205 mg, about210 mg, about 215 mg, about 220 mg, about 225 mg, about 230 mg, about 235 mg, about 240 mg, about 245 mg, about 250 mg, about 255 mg, about 260 mg, about 265 mg, about 270 mg, about 275 mg, about 280 mg, about 285 mg, about 290 mg, about 295 mg, about 300 mg, about 350 mg, about400 mg, about 450 mg, about 500 mg, about 550 mg, about 600, about 650, or about 700 mg per tablet.

[0080] In some embodiments, the dosage for a specific tablet (i.e., API) may include more than one tablet. For example the dosage for a human for a certain API may be one tablet, two tablets, three tablets, four tablets, etc. In a certain embodiment, the dosage for acetaminophen (APAP) and / or aspirin (ASA) may be about 325 mg to about 1000 mg (about 162.5 mg to about 500 mg per tablet).

[0081] In some embodiments, the dosage for Dextromethorphan HBr may be about 10 mg to about 30 mg for adults and about 5 mg to about 15 mg for kids (could be one or 2 tablets so range would be about 2.5 mg to about 30 mg per tablet). In some embodiments, the dosage for CPM may be about 4 mg for adults and about 2 mg for kids (could be one or 2 tablet so range would be about 1 mg to about 2 mg per tablet). In some embodiments, the dosage for DOX may be about 7.5 mg to about 12.5 mg for adults and about 3.75 mg to about 6.25 mg for kids (could be one or two tablets so range would be about 3.125 mg to about 12.5 mg per tablet). In some embodiments, the dosage for PSE may be about60 mg for adults, about 30 mg for older kids, and about 15 mg for younger kids (range would be about7.5 mg to about 60 mg per tablet).Pharmaceutically acceptable excipient

[0082] The oral pharmaceutical composition also includes one or more pharmaceutically acceptable excipient / additive. Suitable additives are all customary formulation auxiliaries. Nonlimiting examples of pharmaceutically acceptable excipients include sweeteners, flavoring agents, lubricants, extenders, solvents or diluents, solid carriers and fillers, surfactants, glidants, dispersants or binders or fixatives, preservatives, dyes and pigments, defoamers, inorganic and organic thickeners, water repellants, and other further processing auxiliaries. In certain embodiments, flavors and / or sweeteners may be added to the composition(s) to make the end oral pharmaceutical composition more palatable to a consumer. In an example embodiment, the oral pharmaceutical composition may include silicon dioxide, such as silicon dioxide colloidal.

[0083] A non-limiting list of flavoring agents includes natural flavoring agents (such as those derived from natural sources like plants, fruits, and vegetables), artificial flavoring agents (such as vanillin synthetically produced for a vanilla flavor), processed flavoring agents (such as smoked flavors, roasted flavors, and fermented flavors), masking agents (such as salt) and sweeteners. Suitable flavoring agents include, but are not limited to, vanilla extract, cinnamon, ginger, citrus oils, orange flavor, cherry flavor, grape flavor, strawberry flavor, and cooling flavor. A flavoring agent may be present in one or more of the disclosed oral pharmaceutical composition in an amount of about 0.1-10 wt. % or about 1-3 wt. %. In some embodiments, an oral pharmaceutical composition may include at least about 1 wt. %, about 2 wt. %, about 3 wt. %, about 4 wt. %, about 5 wt. %, about 6 wt. %, about 7 wt. %, about 8 wt. %, or about 9 wt. % flavoring agents.

[0084] A non-limiting list of sweeteners includes sugar (such as sucrose, fructose, and glucose), sugar alcohol (such as erythritol and maltitol), sugar substitute (such as aspartame, acesulfame potassium (Ace K), sucralose, and stevia), syrups, honey, molasses, glycyrrhizin, unrefined sweetener (such as coconut sugar), and allulose.

[0085] In some embodiments, colorants such as inorganic pigments can be included in the oral pharmaceutical composition. Examples of inorganic pigments include iron oxide, titanium oxide, Prussian blue, and organic dyes, such as alizarin dyes, azo dyes, and metal phthalocyanine dyes, and trace nutrients, such as salts of iron, manganese, boron, copper, cobalt, molybdenum, and zinc. Additional suitable colorants can include, but are not limited to, orange speckles, red speckles, purplecolor, and pink color. A colorant may be present in one or more of the oral pharmaceutical compositions in an amount of about 0.001-5 wt. % or about 0.001-0.1 wt. %. In some embodiments, an oral pharmaceutical composition may include at least about 0.001 wt. %, about 0.01 wt. %, about 0.1 wt. %, about 1 wt. %, about 2 wt. %, about 3 wt. %, or about 4 wt. % colorants.

[0086] In some embodiments, the oral pharmaceutical composition may include one or more superdisintegrants. In some embodiments, the oral pharmaceutical composition may comprise about 1-15 wt. % or about 3-5 wt. % of one or more superdisintegrants. In some embodiments, an oral pharmaceutical composition may include less than or equal to about 15 wt. %, about 12 wt. %, about 10 wt. %, about 8 wt. %, about 5 wt. %, about 4 wt. %, about 3 wt. %, or about 2 wt. % of one or more superdisintegrants. In some embodiments, an oral pharmaceutical composition may include at least about 1 wt. %, about 2 wt. %, about 3 wt. %, about 4 wt. %, about 5 wt. %, about 8 wt. %, about 10 wt. %, or about 12 wt. % of one or more superdisintegrants. Suitable superdisintegrants may include, but are not limited to crospovidone, croscarmellose, croscarmellose sodium, sodium starch glycolate, and starch (e.g., partially pre-gelatinized corn starch). In some embodiments, the oral pharmaceutical composition may include both croscarmellose sodium and sodium starch glycolate. In some embodiments, the gelatin-comprising composition may include equal amounts of croscarmellose sodium and sodium starch glycolate. In some embodiments, one or more superdisintegrants may include only starch. In some embodiments, including two superdisintegrants may provide a synergistic effect (more than additive) of disintegration in some oral pharmaceutical compositions.

[0087] Other additives may also be present in the oral pharmaceutical composition. For example, such additional components may include protective colloids, binders, adhesives, thickeners, thixotropic substances, penetrants, stabilizers, sequestering agents, and complex formers. In general, the active compounds can be combined with any solid or liquid additive customarily used for formulation purposes.

[0088] Other additives may also be present in one or more of the disclosed oral pharmaceutical compositions. For example, such additional components may include protective colloids, binders, adhesives, thickeners, thixotropic substances, penetrants, stabilizers, sequestering agents, and complex formers. In general, the active compounds can be combined with any solid or liquid additive customarily used for formulation purposes. For example, cellulose, pre-gelatinized starch, hydroxypropyl cellulose, fruit pectin powder, hydroxyethyl cellulose, or a combination thereof, may be included to thicken, stabilize, or add texture to the oral pharmaceutical composition. In some embodiments, an additive may be present in one or more of the disclosed compositions in an amountof about 0.1 wt. % to about 0.5 wt. %, about 0.5 wt. % to about 1.0 wt. %, about 1.0 wt. % to about 5.0 wt. %, about 5.0 wt. % to about 10 wt. %, about 10 wt. % to about 20 wt. %, about 20 wt. % to about 30 wt. %, about 30 wt. % to about 40 wt. %, about 40 wt. % to about 50 wt. %, about 50 wt. % to about 60 wt. %, 60 wt. % to about 70 wt. %, 70 wt. % to about 80 wt. %, 80 wt. % to about 90 wt. %, 90 wt. % to about 99 wt. %, about 1 wt. % to about 50 wt. %, about 5 wt. % to about 45 wt. %, about 10 wt. % to about 40 wt. %, and about 20 wt. % to about 40 wt. %, about 50 wt. % to about 99 wt. %, about 60 wt. % to about 90 wt. %, or about 70 wt. % to about 80 wt. %, based on the total weight of the oral pharmaceutical composition.D. MethodsMethod of making the oral pharmaceutical composition

[0089] A method of making the oral pharmaceutical composition described herein is also disclosed. The method may include compressing a powder blend to form the oral pharmaceutical composition, wherein the powder blend includes a desiccant, a lubricant combination, an effervescent combination, one or more active pharmaceutical ingredient (API), and one or more pharmaceutically acceptable excipient. Additionally or alternatively, the method may include compressing a powder blend to form the oral pharmaceutical composition, wherein the powder blend includes a means for controlling moisture content, a means for reducing friction between granules, an effervescent combination, one or more active pharmaceutical ingredient, and one or more pharmaceutically acceptable excipient is provided herein.

[0090] The oral pharmaceutical composition described herein can be prepared by known methods.

[0091] In some embodiments, the oral pharmaceutical composition, such as a compressed tablet, is capable of or configured to dissolve in water. In some embodiments, the oral pharmaceutical composition may be generated via known methods such as dry granulation, direct compression, etc. In some embodiments, the oral pharmaceutical composition may be dry. In some embodiments, a powder comprising a desiccant, a lubricant combination, an effervescent combination, one or more active pharmaceutical ingredient (API), and one or more pharmaceutically acceptable excipient may be compressed using conventional tableting equipment, such as a Flexitab® tablet press. Additionally or alternatively, in some embodiments, a powder comprising means for controlling moisture content, a means for reducing friction between granules, an effervescent combination, one or more active pharmaceutical ingredient, and one or more pharmaceutically acceptable excipient may be compressed using conventional tableting equipment, such as a Flexitab® tablet press. The powder may becompressed into tablets of various size and weight ranges. For example, in some embodiments, the oral pharmaceutical composition (e.g., tablet) may be about 50 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about lOOOmg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg, about 1800 mg, about 1900 mg, about 2000 mg, about 2100 mg, about 2200 mg, about 2300 mg, about 2400 mg, about 2500 mg, about 2600 mg, about 2700 mg, about 2800 mg, about 2900 mg, or about 3000 mg. In some embodiments, the oral pharmaceutical composition may be at least about 200 mg. In a specific embodiment, the oral pharmaceutical composition may be about 250 mg. In another embodiment, the oral pharmaceutical composition may be about 1000 mg. In some embodiments, the oral pharmaceutical composition may be in any general shape (e.g., sphere, cube, cylinder, etc.). In some embodiments, the oral pharmaceutical composition may dissolve in water.

[0092] The oral pharmaceutical composition described herein may be an oral dosage form. The oral dosage form may be a solid oral dosage form such as a tablet, powder, pill, granule, chewing gum, candy, and an extruded form, such as a rod. In a particular embodiment, the solid oral dosage form is a tablet, for example a pressed tablet. In certain embodiments, the tablet is a chewable tablet. In another embodiment, the solid oral dosage form, such as a pressed tablet, is capable of or configured to dissolve in the mouth (in situ) rather than having to be added to water, such as a powder formulation, which is added to water and then consumed by a subject. In some embodiments, the solid oral dosage form can dissolve in the mouth without the addition of water. In other words, in some embodiments the solid oral dosage form can dissolve in the mouth using / with only saliva.

[0093] In some embodiments, the oral pharmaceutical composition may have a hardness of about 5 kP to about 14 kP, about 6 kP to about 13 kP, about 6 kP to about 12 kP, about 7 kP to about 12 kP, about 8 kP to about 11 kP, about 9 kP to about 10 kP, about 6 kP to about 12 kP, about 6 kP to about 11 kP, about 6 kP to about 10 kP, about 6 kP to about 9 kP, about 6 kP to about 8 kP, about 6 kP to about 7 kP, about 7 kP to about 13 kP, about 8 kP to about 13 kP, about 9 kP to about 13 kP, about 10 kP to about 13 kP, about 11 kP to about 13 kP, or about 12 kP to about 13 kP. In certain embodiments, the oral pharmaceutical composition may have a hardness of about 6 kP to about 12 kP. In certain embodiments, the oral pharmaceutical composition may have a hardness of about 6 kP to about 13 kP.

[0094] Ejection force as referred to herein is the force required to push the tablet out of the tablet press. In some embodiments, ejection force may help measure how well lubricated a formulation is.In some embodiments, the tablet can be ejected from tableting equipment with an ejection force of about 100 N to about 1000 N, about 200 N to about 900 N, about 300 N to about 800 N, about 350 N to about 750 N, about 400 N to about 700 N, about 450 N to about 650 N, about 500 N to about 600 N, about 525 N to about 675 N, about 100 N to about 900N, about 100 N to about 800 N, about 100 N to about 700 N, about 100 N to about 600 N, about 100 N to about 500 N, about 100 N to about 400 N, about 100 N to about 300 N about WO N to about 200 N, about WO N to about 150 N, about 150 to about WOO N, about 200 to about WOO N, about 300 to about WOO N, about 400 to about WOO N, about 500 to about WOO N, about 600 to about WOO N, about 700 to about WOO N, about 800 to about WOO N, about 900 to about WOO N, or about 950 to about WOO N. In certain embodiments, the tablet can be ejected from tableting equipment with an ejection force of about 100 N to about 600 N.

[0095] It is understood that the above examples are non-limiting, and for any oral pharmaceutical composition containing an API, it may be appropriate to add therein the effervescent combination, lubricant combination, a desiccant, and / or pharmaceutically acceptable excipient according to the present disclosure.Use / Method of TreatmentD. Use / Method of Treatment

[0096] In a further embodiment, a method is provided herein for treating one or more health conditions comprising administering an oral pharmaceutical composition described herein to a subject or patient. A non-limiting list of health conditions includes nutritional deficiencies, allergies, common cold and cold-like symptoms, cancer, bacterial infections, fungal infections, viral infections, diabetes, food poisoning, pain, such as headaches, kidney disease, etc.

[0097] In some embodiments, treatment includes an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired clinical results may include one or more of the following: a) inhibiting the disease or condition, (e.g., decreasing one or more symptoms resulting from the disease or condition, and / or diminishing the extent of the disease or condition); b) slowing or arresting the development of one or more clinical symptoms associated with the disease or condition (e.g., stabilizing the disease or condition, preventing or delaying the worsening or progression of the disease or condition, and / or preventing or delaying the spread (e.g., metastasis) of the disease or condition); and / or c) relieving the disease, that is, causing the regression of clinical symptoms (e.g., ameliorating the disease state, providing partial or total remission of the disease or condition,enhancing effect of another medication, delaying the progression of the disease, increasing the quality of life, and / or prolonging survival).

[0098] In some embodiments, prevention includes treatment of a disease or condition that causes the clinical symptoms of the disease or condition not to develop or progress. Oral pharmaceutical compositions may, in some embodiments, be administered to a subject (including a human) who may be at risk or may have a family history of the disease or condition in order to prevent the disease or condition.

[0099] In some embodiments, methods are provided herein for treating and / or preventing allergies and / or pain (e.g., hay fever, hives, conjunctivitis, and reactions to insect bites or stings). In some embodiments, the method comprises administering to a patient an oral pharmaceutical composition comprising an API, such as Dex. HBr, acetaminophen, or a pharmaceutically acceptable salt thereof. In some embodiments, the method comprises administering to a patient an oral pharmaceutical composition comprising nutritional ingredients such as calcium carbonate, and vitamins such as ascorbic acid (vitamin C), tocopherols (vitamin E), and retinols (vitamin A).EXAMPLES

[0100] The following examples are merely illustrative, and do not limit this disclosure in any way.

[0101] All formulations may contain External lubrication (Trace amount) - Zn stearate / Citric acid anhydrous (90 / 10).

[0102] EXAMPLE 1: Lubricant experiments

[0103] Multiple ratios of magnesium stearate and stearic acid were evaluated. Formulation 1 (Table 1) included 1% magnesium stearate. However, the tablet was too soft at less than about 3 kP (lower than the target tablet hardness range of 6 kP to 12 kP) and had a high ejection force (over 1000 N). Due to tablet softness, tablet compression profile data (e.g., ejection force, etc.) could not be calculated.

[0104] Table 1. Formulation 1 (magnesium stearate as lubricant)

[0105] Next, magnesium stearate was replaced by stearic acid, and microcrystalline cellulose (MCC) was added in Formulation 2 (Table 2). Figure 1 shows that as compression force increases, tablet hardness and ejection force also increase. However, the ejection force was no more than 500 N, even with the compression force and tablet hardness at the highest limit. Tablet hardness was significantly increased and ejection force was reduced compared to Formulation 1. However, high ejection stress such as punch sticking (i.e., sticking to the tablet press) and tablet chipping (i.e., when the tablet becomes dented or chipped, typically around the tablet’s edges during compression) were observed during the compression process.

[0106] Table 2: Formulation 2 (stearic acid as lubricant)

[0107] Formulations containing magnesium stearate and stearic acid were evaluated on tablet chipping, punch sticking, ejection force, and tablet hardness (Table 3). Formulation 3 only contained 2% stearic acid (no magnesium stearate). Formulation 4 included 2% stearic acid and 1% magnesium stearate. Formulation 5 included 2% stearic acid and 0.5% magnesium stearate.

[0108] Table 3: Formulations 3, 4, and 5[001091 Upon running compression studies on Formulations 3, 4, and 5 on a Fette tablet press 1200i, a Formulation 3 tablet was observed as capping and punch sticking when the formulation contains stearic acid only as the lubricant. Formulation 4 had lower tablet hardness (less than about 3 kP) compared to Formulation 5. Due to softness of these tablets, tablet compression profile data could not be collected. Formulation 5 achieved the target tablet hardness profile (about 6 kP to about 12 kP) and the maximum tablet hardness was 13 kP (Fig. 2). Fig. 2 shows that when the compression force is too high, tablet fracturing occurs and tablet hardness decreases. Such over-compression is a common tablet compression profile. No capping and tablet punch sticking were observed during tablet compression, and the ejection force was kept in the low range of 300-400 N. Formulations 4 and 5 maintained similar ejection force, likely due to the same level of 2% stearic acid, while Formulation5 had a slightly higher ejection force at a main compression force of 60 KN. Fig. 3 shows that with the higher amount of Mg stearate the low ejection force can be extended into a higher force compression range, making the tablet and tableting process more robust.

[0110] Without being bound by theory, adding stearic acid allowed the ejection force to be lowered compared to Formulation 1, while maintaining the tablet hardness profile, and magnesium stearate significantly impacted tablet hardness and reduced punch sticking and tablet capping during the compression process.

[0111] EXAMPLE 2: Beta-cyclodextrin experiments

[0112] In tablets that contain effervescent combinations, moisture control can help keep the effervescent reaction from activating prematurely. An analysis of the moisture content of the excipients used herein, in Formulation 6 (see, Table 4), identified Kleptose® with a moisture level of up to 14% and a level of more than 20% w / w in the formulation as the main contributor to the moisture level, but other excipients also contribute to the moisture. The inventors conducted the following experiments to try and minimize the moisture level of Kleptose® to keep the loss-on-drying (LOD) of ingredients as low as possible while maintaining tablet compressibility. To determine LOD, the formulation is put in an oven at 105°C and is dried until it does not lose any more weight. The % of weight referred to is the LOD. For most formulations, the weight is lost from water evaporating from the powder and one is left with a dry sample, hence the term loss on drying. However, not only water can evaporate, and other solvents or volatile compounds can also evaporate and can cause weight loss.

[0113] When comparing the structure of different grades of Kleptose® (beta-cyclodextrin), it was found that there was a difference in the structure of Kleptose®, which ultimately had an impact on tablet compressibility. Fig. 4 shows the microscopic structure of the different grades of Kleptose® particles (Kleptose® DC, 4% and 7%). Kleptose® 7% and Kleptose® 4% have moisture levels of less than 7% w / w and 4% w / w, respectively. Kleptose® is partially amorphous for better tablet compressibility. Kleptose® DC has a brittle, partially amorphous structure, whereas Kleptose® 4% and 7% is shown to have a rigid, crystalline structure. The formulation in Table 4 (either with Kleptose® DC / Kleptose® DC Dried / Kleptose® 7%, or Kleptose® 4%) was used to investigate the impact of the amorphous content on compressibility potential. It was noticed that the moisture content had a larger impact on the compressibility (hardness) than the amorphous content (Table 5). Table 5 shows that higher moisture yields harder tablets, while lower moisture yields softer tablets. D10, D50, and D90 are percentile size values and are read from the cumulative particle size distribution. D10,D50, and D90 indicate the size below which 10%, 50%, and 90%, respectively, of all particles are found. Thus, DIO, D50, D90 are the 10th, 50th and 90th percentile of a particle size distribution. To determine this, one can measure how big are all the particles are and note the middle size (50th percentile, D50) which means half the particles are bigger and half the particles are smaller. For D10 it means 10% of the particles are smaller and 90% are bigger. D90 is the opposite, as 90% are smaller and 10% are bigger. The partially amorphous content of Kleptose® DC, with its lower density, is to aid in the compressibility of the tablet, providing better compressibility characteristics. Kleptose® DC may allow for more compressibility due to its different moisture uptake potential. Amorphous materials tend to pick up moisture more readily than highly crystalline compounds. Fig. 4 also shows that Kleptose® DC absorbs moisture more readily and to a higher extent as compared to the crystalline one. Thus, the increased moisture content may be responsible for Kleptose® DC generating harder tablets. Although Kleptose® DC generated a tablet with 20.3 kP hardness, it should be understood that one can adjust the hardness of a tablet by not applying as much force during the compression process. But for the present experiment, manufacturing parameters were kept constant.

[0114] Table 4: Formulation 6

[0115] Table 5: Maximum Hardness of different Kleptose® grades

[0116] Initial studies indicated that using any of the dried Kleptose® grades (Kleptose® DC, Kleptose® DC Dried , Kleptose® 4%, and Kleptose® 7%) resulted in tablets in which the effervescent combination is not activated (due to internal moisture incorporated into the tablets through choice of excipients used in the formulation) at elevated temperatures. Thus, Kleptose® 7% was used in the next experiments due to commercial availability. During scale up studies, it was noticed that tablet compressibility was also strongly influenced by the particle size of the material. Within each grade of Kleptose®, it was found that the variability in the particle size has an effect on compressibility. When experimenting with various lot numbers of Kleptose® 7%, with varying particle size distribution, the compression profile of the tablet changed. Table 6 shows the relationship between particle size and hardness (compressibility). To note, X0017 and X0018 represent the different lot numbers used. Smaller particle size (represented in DIO, D50, and D90) yields higher tablet hardness (Table 6).

[0117] Table 6 - Relationship between Kleptose® Particle Size Distribution (PSD) of DifferentLots and Hardness

[0118] Kleptose® 7% is produced by drying standard Kleptose® to the desired moisture level of not more than 7%. Kleptose® 200F is produced through sieving of standard Kleptose® such that the retains on a 1000 pm sieve, a 200 pm sieve, and a 40 pm sieve are NMT 1%, 5%, and 50%, respectively.

[0119] As the particle size, moisture level, and structure of Kleptose® have an impact on the compressibility of the tablets, the inventors tried controlling these variables. A new variant of Kleptose® 7% was produced called Kleptose® 200F 7%, containing beta-cyclodextrin that is moisture-controlled within the LOD specifications of Kleptose® 7%, while also having controlled particle size, utilizing particle size controlled through using Kleptose® 200F as the starting material for the drying process. This also provides a crystalline form of the Kleptose® with less potential to pick up additional moisture, especially in the range below 30% relative humidity (RH), in which typical manufacturing takes place. Table 7 and Fig. 5 outlines how the hardness of the tablets is impacted by the moisture content of Kleptose®. A preferred moisture content of Kleptose® may be about 5.0% to about 7.0% to maintain a desired tablet hardness of about 6 kP to about 12 kP.

[0120] Table 7 - Kleptose® 200F hardness at different moisture levels (lot X00DI was used to keep the particle size constant)

[0121] The addition of dried Kleptose® to the formulation not only aids in the non-activation of the effervescent combination but can also be used for stabilizing moisture sensitive APIs such as Aspirin. The remaining moisture content present in the tablets may be redistributed to the Kleptose®, thus making it unavailable to react with other components. Using dried Kleptose®, Aspirin, and an effervescent combination hindered the Aspirin hydrolysis when dried Kleptose® is part of the formulation. Fig. 6 indicates free salicylic acid (FSA) level (one of the degradation products formed from Aspirin, also referred to as Acetyl Salicylic Acid (ASA)) at shelf life to be below 4% compared to the limit of 8% typically approached by other formulations not containing Kleptose®.

[0122] EXAMPLE 3: Additional Formulations

[0123] Additional formulations (Formulations 7-11) including 2% stearic acid and 0.5%magnesium stearate were generated as recited in Tables 8-12.

[0124] Table 8: Formulation 7

[0125] Table 9: Formulation 8

[0126] Table 10: Formulation 9

[0127] Table 11: Formulation 10

[0128] Table 12: Formulation 11

[0129] EXAMPLE 4: Stability Assays

[0130] Stability assays were performed to test how different desiccants (Starch 1500®, 3% Starch, and 20% Kleptose® Lot) affect aspirin degradation. FSA (salicylic acid) is the main degradant when aspirin degrades. Internal desiccants were added to the formulations in Table 13 and tested to determine if they could stabilize aspirin. Samples were stored at 40°C / 75% RH (relative humidity) for up to 12 weeks. While each desiccant may slow the degradation of aspirin, Kleptose® 20% may slow aspirin degradation the most, as the % of FSA after 12 weeks was only 2.3%, compared to 2.5% (Starch 3%) and 7.6% (Start 1500®) (Table 14).

[0131] Table 13: Formulations for desiccant stability assay

[0132] Table 14: Desiccant stability assay results

[0133] Additionally, stability assays were performed to test how different levels of effervescent couple (0%, 50%, 100%, and 200%) affect aspirin degradation. FSA (salicylic acid) is the main degradant when aspirin degrades. Different levels of effervescent couple were added to the formulations in Table 15 and tested to determine if they could stabilize aspirin. Samples were stored at 40°C / 75% RH (relative humidity) and packed in a laminated aluminum foil pouch. While each level of effervescent couple may slow the degradation of aspirin, lower percentages of effervescent couple may lower aspirin degradation (Table 16).

[0134] Table 15: Formulations for levels of effervescent couple stability assay

[0135] Table 16: Levels of effervescent couple stability assay results

[0136] Additionally, stability assays were performed to test how different levels of citric acid (.075mM excess, 1.0 mM excess, and 1.5mM excess) affect aspirin degradation (Table 18). FSA (salicylic acid) is the main degradant when aspirin degrades. Different levels of citric acid were added to the formulations in Table 17 and tested to determine if they could stabilize aspirin. Samples were stored at 40°C / 75% RH and packed in a laminated aluminum foil pouch.

[0137] Table 17: Formulations for levels of citric acid stability assay

[0138] Table 18: Levels of citric acid stability assay results

[0139] Additionally, stability assays were performed to test how different concentrations of Kleptose® affect aspirin degradation. FSA (salicylic acid) is the main degradant when aspirin degrades. Different concentrations of Kleptose® were added to the formulations in Table 19 and tested to determine if they could stabilize aspirin. While each concentration of Kleptose® may slow the degradation of aspirin, it seems a higher Kleptose® concentration may lower aspirin degradation more than a lower Kleptose® concentration (Table 20).

[0140] Table 19: Formulations for different concentrations of Kleptose® assay

[0141] Table 20: Different Kleptose® concentration stability assay results

Claims

WHAT IS CLAIMED IS:

1. An oral pharmaceutical composition comprising: a desiccant; a lubricant combination; an effervescent combination; one or more active pharmaceutical ingredient (API); and one or more pharmaceutically acceptable excipient.

2. The composition of claim 1, wherein the desiccant comprises a cyclodextrin or a starch.

3. The composition of claim 2, wherein the desiccant comprises a cyclodextrin, preferably a betacyclodextrin.

4. The composition of claim 3, wherein the beta-cyclodextrin is crystalline.

5. The composition of claim 3, wherein the beta-cyclodextrin is partially amorphous.

6. The composition of any one claims 3-5, wherein beta-cyclodextrin has a moisture content of about 4.0% to about 9.0%, preferably about 5.0% to about 7.0%.

7. The composition of any one of the previous claims, wherein the desiccant has a particle size distribution (PSD) of about 40 pm to about 1,000 pm.

8. The composition of any one of the previous claims, wherein the composition comprises about 0.1% to about 50.0%, preferably about 21.0% desiccant, by weight of the composition.

9. The composition of any one of the previous claims, wherein the composition comprises a molar ratio of desiccant to API of about 3:1 or greater.

10. The composition of claim of any one of the previous claims, wherein the lubricant combination comprises a metal stearate and stearic acid.

11. The composition of claim 10, wherein the composition further comprises calcium palmitate, magnesium palmitate, palmitic acid, or a combination thereof.

12. The composition of claim 10 or claim 11, wherein the metal stearate is magnesium stearate, calcium stearate, zinc stearate, aluminum stearate, barium stearate, lithium stearate, or a combination thereof.

13. The composition of claim of any one of the previous claims, wherein lubricant combination comprises magnesium stearate and stearic acid.

14. The composition of claim 13, wherein the composition comprises about 0.05% to about 5.0% magnesium stearate, preferably about 0.5% magnesium stearate, and about 1.0% to about 10.0%, preferably about 2.0% stearic acid, by weight of the composition.

15. The composition of any one of the previous claims, wherein the effervescent combination comprises citric acid and sodium bicarbonate.

16. The composition of any one of the previous claims, wherein the effervescent combination comprises a molar ratio of about 2:1 to about 3:1 sodium bicarbonate to citric acid.

17. The composition of any one of the previous claims, wherein the one or more API is a moisturesensitive API, such as aspirin, acyclovir, erythromycin base, itraconazole, ketoconazole, or a combination thereof.

18. The composition of any one of the previous claims, wherein the one or more API is a cough suppressant, an analgesic, an antihistamine, a decongestant, an antacid, an antidiarrheal, an antibiotic, an antiviral, a sedative, or a combination thereof.

19. The composition of any one of the previous claims, wherein the one or more API comprises dextromethorphan HBr, benzonatate, codeine, pholcodine, or a combination thereof.

20. The composition of any one of the previous claims, wherein the one or more API is an analgesic comprising acetaminophen (APAP); a COX-2 inhibitor; opioid; alcohol; cannabis; a nonsteroidal anti-inflammatory drug (NSAID), such as aspirin, ibuprofen, and naproxen; or a combination thereof.

21. The composition of any one of the previous claims, wherein the one or more API comprises an antihistamine comprising: an Hi-antihistamine, such as Azelastine, Chlorphenamine (CPM), Hydroxyzine, Loratadine, and Trazodone; an Hi-antihistamine, such as Cimetidine and Ranitidine; H -antihistamines, such as Clobenpropit and Conessine; an H4-antihistamine, such as Thioperamide; a histidine decarboxylase inhibitor, such as Tritoqualine; a mast cell stabilizer, such as Nedocromil; or a combination thereof.

22. The composition of any one of the previous claims, wherein the one or more API is a combination comprising a cough suppressant, analgesic, and an antihistamine.

23. The composition of any one of the previous claims, wherein the one or more API comprises a vitamin, such as vitamin C.

24. The composition of any one of the previous claims, wherein the composition comprises about 0.05 wt. % to about 35% of the one or more API, by weight of the composition.

25. The composition of any one of the previous claims, wherein the oral pharmaceutical composition is a tablet, preferably a chewable tablet.

26. The composition of claim 25, wherein the tablet has a hardness of about 6 kP to about 12 kP.

27. The composition of claim 25 or 26, wherein the tablet can be ejected from tableting equipment with an ejection force of about 100 N to about 1000 N, preferably about 100 N to about 600 N.

28. A method of making the oral pharmaceutical composition of any one of the previous claims, comprising compressing a powder blend to form the oral pharmaceutical composition, wherein the powder blend comprises a desiccant, a lubricant combination, an effervescent combination, one or more active pharmaceutical ingredient (API), and one or more pharmaceutically acceptable excipient.

29. An oral pharmaceutical composition comprising: a means for controlling moisture content; a means for reducing friction between granules; an effervescent combination; one or more active pharmaceutical ingredient (API); and one or more pharmaceutically acceptable excipient.

30. The oral pharmaceutical composition of claim 29, wherein the oral pharmaceutical composition is a tablet, preferably a chewable tablet.

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