Fexofenadine-containing compositions

Abstract

The present disclosure is directed to a process for preparing a spray dried formulation comprising fexofenadine zwitterion dihydrate, comprising spray drying (i) a fexofenadine zwitterion dihydrate composition, and (ii) an inert matrix. The present disclosure also provides products prepared according to the processes described herein, spray dried formulations comprising fexofenadine zwitterion dihydrate and an inert matrix, oral solid dosage forms comprising the spray dried formulations described herein, and a method for alleviating allergy symptoms in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a spray dried formulation or oral solid dosage form described herein.

Description

[Technical field]

[0001] The present disclosure relates to compositions containing fexofenadine, processes for preparing said compositions, and methods of using said compositions. [Background technology]

[0002] Allergies are a troubling part of many people's lives, often affecting the quality of life for adults and children. In many cases, allergies cannot be avoided as they are triggered by indoor and outdoor allergens. Finding a treatment for allergies can be difficult and often depends on the type of allergy and the age of the patient. Various allergy medications are known in the art, including allergy medications that contain fexofenadine hydrochloride. Fexofenadine hydrochloride refers to 4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-α,α-dimethylbenzeneacetic acid hydrochloride, which has the following structure and is available in products such as Goodsense® Aller-ease, Aller-Fex™, Wal-Fex® Allergy, Allegra®, Allegra® Allergy 12 Hour, Allegra® Allergy 24 Hour, Children's Allegra® Allergy, and Mucinex Allergy, Allegra® Allergy, and Children's Wal-Fex®. [ka]

[0003] Fexofenadine hydrochloride has a bitter taste, which may be unpleasant. Fexofenadine hydrochloride solid pharmaceutical preparations available in the art are coated with flavoring agents that mask the bitter taste. Alternatively, fexofenadine hydrochloride is mixed with flavoring agents, but the flavoring agents cannot completely mask the unpleasant bitter taste. In addition to the bitter taste, fexofenadine hydrochloride formulations are difficult to manufacture. For example, drying the fexofenadine hydrochloride formulation results in the loss of a significant amount of fexofenadine hydrochloride, reducing the yield of the final product. Furthermore, because the particles of fexofenadine hydrochloride are very small, there is a possibility that small particles may ignite during the drying process, thereby reducing the yield of the final product and leading to unsafe working conditions. Summary of the Invention

[0004] What is needed are more efficient, sustainable and safe methods for preparing medicines containing fexofenadine.

[0005] In certain embodiments, the present disclosure provides a process for preparing a spray-dried formulation comprising fexofenadine zwitterion dihydrate, comprising spray drying (i) a fexofenadine zwitterion dihydrate composition and (ii) an inert matrix. In other embodiments, the present disclosure provides products prepared according to the processes described herein. In a further embodiment, the present disclosure provides a spray-dried formulation comprising fexofenadine zwitterion dihydrate and an inert matrix. In yet another embodiment, the present disclosure provides a spray-dried formulation comprising fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a buffering agent, a sweetening agent, a binder, a diluent, a disintegrant, a flavoring agent, and a lubricant. In still further embodiments, the present disclosure provides an oral solid dosage form comprising the spray-dried formulation described herein.

[0006] In other embodiments, the present disclosure provides a method of alleviating symptoms due to allergies in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a spray-dried formulation or oral solid dosage form described herein. In a further embodiment, the disclosure provides a method of alleviating symptoms from upper respiratory tract allergy in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the spray-dried formulation or oral solid dosage form described herein. Other aspects and embodiments of the present invention will become readily apparent from the following detailed description of the invention.

[0007] This application will be better understood when read in conjunction with the accompanying drawings. For the purpose of illustrating the subject matter, the drawings show exemplary embodiments of the subject matter, but the subject matter disclosed herein is not limited to the specific compositions, methods, and processes disclosed. Additionally, the drawings are not necessarily drawn to scale. [Brief description of the drawings]

[0008] [Figure 1] FIG. 1 is a bar graph comparing the bitterness of fexofenadine formulations. [Diagram 2] FIG. 2 is a differential scanning calorimetry (DSC) thermogram of fexofenadine hydrochloride. [Diagram 3] FIG. 3 is a DSC thermogram of fexofenadine zwitterion dihydrate. [Figure 4] FIG. 4 compares the DSC thermogram of fexofenadine zwitterion with that of the disclosed spray-dried fexofenadine zwitterion dihydrate. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] As used herein, the singular forms "a," "an," and "the" include plural referents. Reference to a particular numerical value includes at least that particular numerical value unless the context clearly dictates otherwise. Thus, for example, reference to "an entity" refers to at least one of such entities and equivalents thereof known to those of skill in the art. When a value is expressed as an approximation by the use of "about", it will be understood that the particular value forms another embodiment. In general, the use of "about" indicates an approximation that may vary depending on the desired properties sought to be obtained by the disclosed subject matter and is interpreted in the particular context in which it is used. This will be interpreted as normal by those skilled in the art. In some cases, the number of significant figures used for a particular value may be one non-limiting way of determining the scope of the term "about". In other cases, the scale used in a series of values ​​may be used to determine the intended range in which the term "about" can be used for each value. When present, all ranges are inclusive and combinable. That is, when values ​​described in a range are presented, they include all values ​​within that range. As used herein, data are presented with full disclosure of all significant digits; however, one of ordinary skill in the art will recognize that the data may be rounded to one or two decimal places.

[0010] When a list is presented, it is to be understood that each individual element of the list, and every combination of the list, is interpreted as a separate embodiment unless otherwise stated. For example, a list of embodiments presented as "A, B, or C" is interpreted as including the embodiments "A," "B," "C," "A or B," "A or C," "B or C," or "A, B, or C." It should be understood that certain features of the invention that are described herein in the context of separate embodiments for clarity may also be provided in combination in a single embodiment. That is, unless clearly incompatible or excluded, each individual embodiment is considered combinable with any other embodiment, and such combinations are considered to be separate embodiments. Conversely, various features of the invention that are described for brevity in the context of a single embodiment may also be provided separately or in any subcombination. It should be further noted that the claims may be drafted to exclude optional elements. Thus, such statements are intended as a prerequisite for using exclusive language, such as "only," "only," or "negative" limitations in connection with the recitation of claim elements. Finally, while an embodiment may be described as part of a series of steps or as part of a more general structure, each of said steps may also be considered an independent embodiment in its own right.

[0011] The terms "patient" and "subject" as used herein, interchangeably, refer to a mammal. In some embodiments, the patient or subject is a human. In other embodiments, the patient or subject is a veterinary or farm animal, a livestock or pet, or an animal commonly used in clinical research. In some embodiments, the patient is an adult, i.e., 18 years of age or older. In other embodiments, the patient is a child, i.e., under 18 years of age. The term "treating" includes ameliorating a disease or disorder (i.e., preventing or alleviating the onset of a disease or at least one of its clinical symptoms). In some embodiments, "treating" refers to improving at least one physical parameter, which may not be discernible by the subject. In other embodiments, "treating" refers to modulating a disease or disorder physically (e.g., stabilizing a discernible symptom), physiologically (e.g., stabilizing a physical parameter), or both. In further embodiments, "treating" refers to delaying the onset of a disease or disorder.

[0012] process The present disclosure relates to compositions containing fexofenadine in a form that is non-bitter when administered orally. Such compositions can be used in a variety of oral dosage forms and are ready to use, i.e., do not require water for oral administration. In particular, the inventors have discovered that fexofenadine zwitterion dihydrate can be formulated into compositions and oral dosage forms that do not convert to fexofenadine hydrochloride, which has an undesirable bitter taste. In so doing, a non-bitter tasting pharmaceutical product is provided for oral solid dosage forms, thereby enhancing a pleasing user experience (e.g., taste and texture) without a bitter aftertaste.

[0013] The terms "fexofenadine zwitterion" and "fexofenadine zwitterion dihydrate" are used interchangeably and refer to 4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-α,α-dimethylbenzeneacetic acid dihydrate. Fexofenadine zwitterion dihydrate has the following structure: [ka] The process used to prepare the spray dried fexofenadine zwitterion dihydrate formulations is advantageous for several reasons. For example, the process can use conventional technology and in particular does not require specialized equipment, complex reactions, or expensive reagents. Furthermore, the process for preparing fexofenadine zwitterion dihydrate is efficient even for compositions containing high doses of fexofenadine zwitterion dihydrate, unlike those reported in the art. In particular, fexofenadine formulations in the art were very bitter, especially at high doses. The process described herein provides a formulation that is not bitter at any dose.

[0014] A. Preparation of Fexofenadine Zwitterion Dihydrate Compositions Fexofenadine zwitterion dihydrate for use in the spray drying process is prepared as described herein. First, fexofenadine hydrochloride, water, and a wetting agent are combined. In some embodiments, fexofenadine hydrochloride is combined with a solution containing water and a wetting agent. The wetting agent is selected to facilitate incorporation of fexofenadine hydrochloride into water and / or to enhance wettability. Many wetting agents are available, including, but not limited to, poloxamers, polysorbates, or polyoxyl hydrogenated castor oil.

[0015] The term "poloxamer" as used herein refers to a non-ionic triblock copolymer consisting of a central hydrophobic block of polypropylene glycol flanked by two hydrophilic blocks of polyethylene glycol (PEG). Poloxamers are available in the art under the trade names Pluronic, Kolliphor, Lutrol, and Synperonic. In some embodiments, the wetting agent is a poloxamer, such as poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, or combinations thereof. The term "polysorbate" as used herein refers to an oily liquid derived from ethoxylated sorbitan esterified with fatty acids. Polysorbates are available in the art as Kolliphor, Scattics, Alkest, Canarcel, and Tween products. In other embodiments, the wetting agent is a polysorbate such as polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate), polysorbate 40 (polyoxyethylene (20) sorbitan monopalmitate), polysorbate 60 (polyoxyethylene (20) sorbitan monostearate), polysorbate 80 (polyoxyethylene (20) sorbitan monooleate), or SEPITRAP™ 80 (polysorbate 80 and magnesium aluminometasilicate). In further embodiments, the wetting agent is polysorbate 80 or SEPITRAP™ 80, or for example polysorbate 80, or for example SEPITRAP™ 80. In yet other embodiments, the wetting agent is polyoxyl hydrogenated castor oil, such as SEPITRAP™ 4000 (polyoxyl 40 hydrogenated castor oil and magnesium aluminometasilicate). One or more wetting agents can be used. In some embodiments, one wetting agent is used. In other embodiments, two humectants are used, and in further embodiments, three humectants are used.

[0016] After the step of using the wetting agent, the composition is combined with an alkalizing agent. The inventors have found that the use of an alkalizing agent reduces the amount of solids present in the composition, thereby reducing the viscosity. This allows the maximum concentration of fexofenadine hydrochloride to be maintained while spray drying the composition in a later step. Generally, the alkalizing agent is a strong base. The inventors have found that the use of a strong base converts fexofenadine hydrochloride to fexofenadine zwitterion dihydrate in this step with the use of less solids than other routes such as the use of a buffer. In some aspects, the alkalizing agent is potassium hydroxide, calcium hydroxide, sodium hydroxide, or barium hydroxide, among others. In other aspects, the alkalizing agent is potassium hydroxide. In a further aspect, the alkalizing agent is calcium hydroxide. In yet another aspect, the alkalizing agent is sodium hydroxide. In yet a further aspect, the alkalizing agent is barium hydroxide. One or more alkalizing agents can be used. In some embodiments, one alkalizing agent is used. In other embodiments, two alkalizing agents are used. In further embodiments, three alkalizing agents are used. The molar ratio of alkalizing agent to fexofenadine hydrochloride is about 0.8:1 to about 1.2:1. In certain aspects, the molar ratio of alkalizing agent to fexofenadine hydrochloride is about 1:1.

[0017] The pH of the resulting composition can be adjusted in situ with one or more buffering agents to about 5.8 to about 7. In some embodiments, the pH is adjusted to about 5.8, about 5.9, about 6, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, or about 7. In other embodiments, the pH is adjusted to about 5.8 to about 7, about 5.8 to about 6.8, about 5.8 to about 6.6, about 5.8 to about 6.4, about 5.8 to about 6.2, about 5.8 to about 6, 6 to about 7, about 6 to about 6.8, about 6 to about 6.6, about 6 to about 6.4, about 6 to about 6.2, about 6.2 to about 7, about 6.2 to about 6.8, about 6.2 to about 6.6, about 6.2 to about 6.4, about 6.4 to about 7, about 6.4 to about 6.8, about 6.4 to about 6.6, about 6.6 to about 7, about 6.6 to about 6.8, or about 6.8 to about 7. Examples of buffering agents include, but are not limited to, dibasic sodium phosphate 2H2O, monobasic sodium phosphate, citric acid / dibasic sodium phosphate, dibasic sodium phosphate hydrate, succinic acid / sodium hydroxide, citric acid / sodium citrate, sodium citrate hydrate, potassium citrate, maleic acid / sodium hydroxide, fumaric acid / sodium hydroxide, monobasic sodium phosphate hydrate, monobasic potassium phosphate / dibasic sodium phosphate, dibasic sodium phosphate hydrate, dibasic potassium phosphate, dibasic potassium phosphate hydrate. In some embodiments, the buffering agent includes monobasic sodium phosphate, monobasic sodium phosphate hydrate, monobasic potassium phosphate / dibasic sodium phosphate, dibasic sodium phosphate hydrate, dibasic potassium phosphate, or dibasic potassium phosphate hydrate. In other embodiments, the buffering agent is monobasic sodium phosphate, monobasic sodium phosphate hydrate / dibasic sodium phosphate, or dibasic sodium phosphate hydrate, or combinations thereof. In further embodiments, the buffering agent is dibasic and monobasic phosphoric acid. One or more buffering agents can be used. In some embodiments, one buffering agent is used. In other embodiments, two buffering agents are used. In a further embodiment, three buffers are used.

[0018] A sweetener can be combined with the resulting buffer-containing suspension. In some embodiments, the sweetener is selected to provide a pleasant user experience to the patient. In certain embodiments, the sweetener masks the salty taste that may result from NaCl produced when fexofenadine hydrochloride is converted to fexofenadine zwitterion dihydrate. The term "salty taste" as used herein refers to a taste recognized by the human taste buds that corresponds to the same taste as table salt, i.e., NaCl. The salty taste is different from the bitter taste provided by fexofenadine hydrochloride. Also, the salty taste is easier to mask than the bitter taste of fexofenadine hydrochloride. Examples of sweeteners include sucralose, aspartame, acesulfame potassium, saccharin, steviol glycosides, neotame, advantame, sodium saccharin, sodium cyclamate, or ammonium glycyrrhizinate, or combinations thereof. In some embodiments, the sweetener is sucralose. In other embodiments, the sweetener is aspartame. In further aspects, the sweetener is acesulfame potassium. In yet other aspects, the sweetener is saccharin. In still further aspects, the sweetener is steviol glycosides. In other aspects, the sweetener is neotame. In further aspects, the sweetener is advantame. In still other aspects, the sweetener is sodium saccharin. In still further aspects, the sweetener is sodium cyclamate. In other aspects, the sweetener is ammonium glycyrrhizinate. One or more sweeteners may be used. In some embodiments, one sweetener is used. In other embodiments, two sweeteners are used. In further embodiments, three sweeteners are used.

[0019] A binder can be combined with the resulting sweetener-containing suspension. The binder is selected to stabilize, e.g., sterically stabilize, the formulation and to avoid particle aggregation. Examples of binders include, but are not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), or carboxymethylcellulose (CMC), hydroxyethyl methylcellulose (HEMC), or hydroxyethyl cellulose (HEC), or combinations thereof. In some embodiments, the binder is HPMC. In other embodiments, the binder is HPMC having a viscosity of about 4 to about 100,000 mPa.s. In further embodiments, the binder is HPMC 4 mPa.s or HPMC 5 mPa.s. In yet other embodiments, the binder is HPC. In still further embodiments, the binder is PVP. In other embodiments, the binder is CMC. In further embodiments, the binder is HEMC. In still other embodiments, the binder is HEC. The composition can contain one or more binders. In some embodiments, the composition contains one binder. In other embodiments, the composition contains two binders. In further embodiments, the composition contains three binders.

[0020] The fexofenadine zwitterion dihydrate composition, including an alkalizing agent, a buffering agent, a sweetening agent, and a binder, has a pH of about 5.8 to about 7. In some embodiments, the fexofenadine zwitterion dihydrate composition has a pH of about 5.8, about 5.9, about 6, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, or about 7. In other embodiments, the fexofenadine zwitterion dihydrate composition has a pH of about 5.8. In further embodiments, the fexofenadine zwitterion dihydrate composition has a pH of about 5.9. In yet other embodiments, the fexofenadine zwitterion dihydrate composition has a pH of about 6. In yet further embodiments, the fexofenadine zwitterion dihydrate composition has a pH of about 6.1. In other embodiments, the pH of the fexofenadine zwitterion dihydrate composition is about 6.2. In further embodiments, the pH of the fexofenadine zwitterion dihydrate composition is about 6.3. In yet other embodiments, the pH of the fexofenadine zwitterion dihydrate composition is about 6.4. In yet further embodiments, the pH of the fexofenadine zwitterion dihydrate composition is about 6.5. In yet further embodiments, the pH of the fexofenadine zwitterion dihydrate composition is about 6.6. In other embodiments, the pH of the fexofenadine zwitterion dihydrate composition is about 6.7.In further embodiments, the pH of the fexofenadine zwitterion dihydrate composition is about 5.8 to about 7, about 5.8 to about 6.9, about 5.8 to about 6.8, about 5.8 to about 6.7, about 5.8 to about 6.6, about 5.8 to about 6.5, about 5.8 to about 6.4, about 5.8 to about 6.3, about 5.8 to about 6.2, about 5.8 to about 6.1, about 5.8 to about 6, about 5.8 to about 5.9, about 5.9 to about 7, about 5.9 to about 6.9, about 5.9 to about 6.8, about 5.9 to about 6.7, about 5. 9 to about 6.7, about 5.9 to about 6.6, about 5.9 to about 6.5, about 5.9 to about 6.4, about 5.9 to about 6.3, about 5.9 to about 6.2, about 5.9 to about 6.1, about 5.9 to about 6, about 6 to about 7, about 6 to about 6.9, about 6 to about 6.8, about 6 to about 6.7, about 6 to about 6.6, about 6 to about 6.5, about 6 to about 6.4, about 6 to about 6.3, about 6 to about 6.2, about 6 to about 6.1, about 6.1 to about 7, about 6.1 to about 6.9, about 6.1 to about 6.8, about 6.1 to about 6.7, about 6. 1 to about 6.6, about 6.1 to about 6.5, about 6.1 to about 6.4, about 6.1 to about 6.3, about 6.1 to about 6.2, about 6.2 to about 7, about 6.2 to about 6.9, about 6.2 to about 6.8, about 6.2 to about 6.7, about 6.2 to about 6.6, about 6.2 to about 6.5, about 6.2 to about 6.4, about 6.2 to about 6.3, about 6.3 to about 7, about 6.3 to about 6.9, about 6.3 to about 6.8, about 6.3 to about 6.7, about 6.3 to about 6.6, about 6.3 to about 6.5, about 6.3 to about 6.4, about 6.4 to about 7, about 6.4 to about 6.9, about 6.4 to about 6.8, about 6.4 to about 6.7, about 6.4 to about 6.6, about 6.4 to about 6.5, about 6.5 to about 6.9, about 6.5 to about 6.8, about 6.5 to about 6.7, about 6.5 to about 6.6, about 6.6 to about 7, about 6.6 to about 6.9, about 6.6 to about 6.8, about 6.6 to about 6.7, about 6.7 to about 7, about 6.7 to about 6.9, about 6.7 to about 6.8, about 6.8 to about 7, about 6.8 to about 6.9, or about 6.9 to about 7.

[0021] The process for forming fexofenadine zwitterion dihydrate can be carried out using equipment known in the art. In some embodiments, the fexofenadine zwitterion dihydrate composition is prepared using a rotor-stator homogenizer. During the preparation of the fexofenadine zwitterion dihydrate composition, the fexofenadine zwitterion dihydrate particles are suspended and air is incorporated into the composition. This reduces the density of the composition and increases the volume of the composition.

[0022] B. Preparation of Spray-Dried Fexofenadine Zwitterion Dihydrate Formulation The fexofenadine zwitterion dihydrate composition is then spray dried to provide a spray-dried fexofenadine zwitterion dihydrate formulation, e.g., a granule. One feature of the process of the present invention is this formation of granules containing fexofenadine zwitterion dihydrate. The granules produced according to these methods do not taste bitter, and subsequent steps of the granules do not convert the fexofenadine zwitterion dihydrate to fexofenadine hydrochloride. The granules comprise (i) a fexofenadine zwitterion dihydrate composition, and (ii) a spray-dried formulation containing fexofenadine zwitterion dihydrate obtained by spray drying an inert matrix. Spray drying for use herein can be carried out using a number of techniques and equipment. In some embodiments, spray drying is carried out using a fluidized bed and a spray system. The inventors have found that a fluidized bed combines the granulation and drying steps. The spray system provides a well-granulated granule. In some embodiments, the spray system is a top spray. In other embodiments, the spray system is a bottom spray. In a further embodiment, the spray system is tangential. Spray drying is performed using an inert matrix. Components of the inert matrix include one or more pharma- ceutically acceptable excipients. Desirably, the one or more pharma-ceutically acceptable excipients maintain the fexofenadine zwitterion dihydrate form in the granules, i.e., the fexofenadine zwitterion dihydrate is not converted to fexofenadine hydrochloride. In some embodiments, the pharma-ceutically acceptable excipients maintain the pH at about 5.5 to about 7 to avoid the formation of fexofenadine hydrochloride. In other embodiments, the pharma-ceutically acceptable excipients maintain the pH at about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, or about 7. In other embodiments, the pharma- ceutically acceptable excipient is a diluent, binder, glidant, or disintegrant, or a combination thereof.

[0023] Examples of diluents include, but are not limited to, microcrystalline cellulose, mannitol, maltitol, sucrose, erythritol, dibasic calcium phosphate, tribasic calcium phosphate, isomalt, xylitol, maltodextrin, lactose, starch, sorbitol, sucrose, sucrose derivatives, inverted sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, cellulose derivatives, calcium carbonate, calcium lactate, calcium sulfate, or calcium phosphate, or combinations thereof. In some embodiments, the diluent is microcrystalline cellulose. In further embodiments, the diluent is microcrystalline cellulose having a pH of about 5 to about 7.5, e.g., 6.2. In other embodiments, the diluent is mannitol. Mannitol is available in the art as a variety of products. In still other embodiments, the diluent is mannitol having a pH of about 6 to about 7, e.g., 6.3. In further embodiments, the diluent is maltitol. In further embodiments, the diluent is maltitol having a pH of about 5 to about 7. In yet another embodiment, the diluent is sucrose. In a further embodiment, the diluent is sucrose at a pH of about 7. In yet a further embodiment, the diluent is erythritol. In a further embodiment, the diluent is erythritol at a pH of about 5 to about 7. In another embodiment, the diluent is dibasic calcium phosphate. In a further embodiment, the diluent is dibasic calcium phosphate at a pH of about 5.1 to about 7.3, such as about 7.3, or about 5.1, or about 6.1 to about 7.2. In a further embodiment, the diluent is tribasic calcium phosphate. In a further embodiment, the diluent is tribasic calcium phosphate at a pH of about 6.8. In a further embodiment, the diluent is isomalt. In a still further embodiment, the diluent is xylitol. In another embodiment, the diluent is maltodextrin. In a further embodiment, the diluent is maltodextrin at a pH of about 4 to about 7. In a further embodiment, the diluent is lactose. In a still further embodiment, the diluent is starch. In a further embodiment, the diluent is starch having a pH of about 4 to about 8. In yet a further aspect, the diluent is sorbitol. In a further aspect, the diluent is sorbitol having a pH of about 4.5 to about 7. In a further aspect, the diluent is a sucrose derivative.In yet another aspect, the diluent is inverted sucrose. In yet another aspect, the diluent is lactitol. In yet another aspect, the diluent is lactitol having a pH of about 4.5 to about 7. In another aspect, the diluent is erythritol. In yet another aspect, the diluent is erythritol having a pH of about 5 to about 7. In yet another aspect, the diluent is fructose. In yet another aspect, the diluent is glucose. In yet another aspect, the diluent is glucose having a pH of about 4 to about 6. In yet another aspect, the diluent is calcium carbonate. In yet another aspect, the diluent is calcium carbonate having a pH of about 9. In another aspect, the diluent is cellulose. In yet another aspect, the diluent is cellulose having a pH of about 5 to about 7.5. In yet another aspect, the diluent is a cellulose derivative. In yet another aspect, the diluent is calcium carbonate. In yet another aspect, the diluent is calcium lactate. In another aspect, the diluent is calcium sulfate. In yet another aspect, the diluent is calcium phosphate. More than one diluent may be used to form the granules. In some embodiments, the granules are formed using one diluent. In other embodiments, the granules are formed using two diluents. In further embodiments, the granules are formed using three diluents.

[0024] Examples of disintegrants in the granules include, but are not limited to, croscarmellose sodium, sodium starch glycolate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or combinations thereof. In some aspects, the disintegrant is croscarmellose sodium. In other aspects, the disintegrant is sodium starch glycolate. In further aspects, the disintegrant is crospovidone. In still other aspects, the disintegrant is pregelatinized starch. In still further aspects, the disintegrant is starch. In other aspects, the disintegrant is hydroxypropyl cellulose (HPC). Two or more disintegrants may be used to form the granules. In some embodiments, the granules are formed using one disintegrant. In other embodiments, the granules are formed using two disintegrants. In further embodiments, the granules are formed using three disintegrants. Examples of glidants in granules include, but are not limited to, talc and silicon dioxide. In some aspects, the glidant is talc. In other aspects, the glidant is silicon dioxide. Two or more glidants may be used to form the granules. In some embodiments, the granules are formed using one glidant. In other embodiments, the granules are formed using two glidants.

[0025] Examples of binders in the granules include, but are not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), or carboxymethyl cellulose (CMC), hydroxyethyl methylcellulose (HEMC), or hydroxyethyl cellulose (HEC), or combinations thereof. In some aspects, the binder is HPMC. In other aspects, the binder is HPMC having a viscosity of about 4 to about 100,000 mPa.s. In further aspects, the binder is HPMC 4 mPa.s or HPMC 5 mPa.s. In still other aspects, the binder is HPC. In still further aspects, the binder is PVP. In other aspects, the binder is CMC. In further aspects, the binder is HEMC. In still other aspects, the binder is HEC. Two or more binders may be used to form the granules. In some embodiments, the granules are formed using one binder. In other embodiments, the granules are formed using two binders. In a further embodiment, the granules are formed using three binders.

[0026] C. Preparation of Fexofenadine Zwitterion Dihydrate Final Drug Product After formation of the spray-dried granules / formulations containing fexofenadine zwitterion dihydrate, a further step may be performed to incorporate an external phase, hi some embodiments, an external phase is included and integrated with the granules. In some embodiments, the external phase is provided by combining the spray-dried formulation with one or more of a second portion of a disintegrant, a second disintegrant, a second portion of a diluent, a flavoring agent, a second portion of a wetting agent, one or more lubricants, or combinations thereof.

[0027] In certain embodiments, the spray-dried formulation is combined with the second portion of the disintegrant used to prepare the granule. Examples of disintegrants in the external phase include, but are not limited to, croscarmellose sodium, sodium starch glycolate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or combinations thereof. In some aspects, the disintegrant in the external phase is croscarmellose sodium. In other aspects, the disintegrant in the external phase is sodium starch glycolate. In further aspects, the disintegrant in the external phase is crospovidone. In yet other aspects, the disintegrant in the external phase is pregelatinized starch. In still further aspects, the disintegrant in the external phase is starch. In other aspects, the disintegrant in the external phase is hydroxypropyl cellulose (HPC). In other embodiments, the spray-dried formulation is combined with a second disintegrant. Examples of the second disintegrant are sodium starch glycolate, crospovidone, pregelatinized starch, starch, hydroxypropyl cellulose (HPC), or combinations thereof. In some aspects, the second disintegrant is sodium starch glycolate. In other aspects, the second disintegrant is crospovidone. In further aspects, the second disintegrant is pregelatinized starch. In yet other aspects, the second disintegrant is starch. In still further aspects, the second disintegrant is HPC.

[0028] In further embodiments, the spray-dried formulation is combined with a second portion of the diluent used to form the granules. Examples of diluents include, but are not limited to, microcrystalline cellulose, mannitol, maltitol, sucrose, erythritol, dibasic calcium phosphate, tribasic calcium phosphate, isomalt, xylitol, maltodextrin, lactose, starch, sorbitol, sucrose, sucrose derivatives, inverted sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, cellulose derivatives, calcium carbonate, calcium lactate, calcium sulfate, or calcium phosphate, or combinations thereof. In some embodiments, the diluent is microcrystalline cellulose. In further embodiments, the diluent is microcrystalline cellulose with a pH of about 5 to about 7.5, e.g., 6.2. In other embodiments, the diluent is mannitol. In yet other embodiments, the diluent is mannitol with a pH of about 6 to about 7, e.g., 6.3. In further embodiments, the diluent is maltitol. In a further aspect, the diluent is maltitol having a pH of about 5 to about 7. In yet another aspect, the diluent is sucrose. In a further aspect, the diluent is sucrose having a pH of about 7. In yet a further aspect, the diluent is erythritol. In a further aspect, the diluent is erythritol having a pH of about 5 to about 7. In another aspect, the diluent is dicalcium phosphate. In a further aspect, the diluent is dicalcium phosphate having a pH of about 5.1 to about 7.3, such as about 7.3, or about 5.1, or about 6.1 to about 7.2. In a further aspect, the diluent is tricalcium phosphate. In a further aspect, the diluent is tricalcium phosphate having a pH of about 6.8. In yet another aspect, the diluent is isomalt. In a still further aspect, the diluent is xylitol. In another aspect, the diluent is maltodextrin. In a further aspect, the diluent is maltodextrin having a pH of about 4 to about 7. In a further aspect, the diluent is lactose. In yet another aspect, the diluent is starch. In a further embodiment, the diluent is starch having a pH of about 4 to about 8. In yet a further aspect, the diluent is sorbitol. In a further aspect, the diluent is sorbitol having a pH of about 4.5 to about 7.In further aspects, the diluent is a sucrose derivative. In yet other aspects, the diluent is inverted sucrose. In still further aspects, the diluent is lactitol. In still further aspects, the diluent is lactitol having a pH of about 4.5 to about 7. In other aspects, the diluent is erythritol. In still further aspects, the diluent is erythritol having a pH of about 5 to about 7. In still further aspects, the diluent is fructose. In still other aspects, the diluent is glucose. In still further aspects, the diluent is glucose having a pH of about 4 to about 6. In still further aspects, the diluent is calcium carbonate. In still further aspects, the diluent is calcium carbonate having a pH of about 9. In other aspects, the diluent is cellulose. In still further aspects, the diluent is cellulose having a pH of about 5 to about 7.5. In still further aspects, the diluent is a cellulose derivative. In still further aspects, the diluent is calcium carbonate. In still further aspects, the diluent is calcium lactate. In other aspects, the diluent is calcium sulfate. In a further aspect, the diluent is calcium phosphate.

[0029] In yet other embodiments, the spray-dried formulation is combined with flavoring agents approved for human use by the US FDA. In yet a further aspect, the spray-dried formulation is combined with a second portion of a wetting agent. Examples of wetting agents include, but are not limited to, poloxamer, polysorbate, or polyoxyl hydrogenated castor oil. In some embodiments, the wetting agent is a poloxamer, such as poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, or a combination thereof. In other embodiments, the wetting agent is a polysorbate, such as polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate), polysorbate 40 (polyoxyethylene (20) sorbitan monopalmitate), polysorbate 60 (polyoxyethylene (20) sorbitan monostearate), polysorbate 80 (polyoxyethylene (20) sorbitan monooleate), or SEPITRAP™ 80 (polysorbate 80 and magnesium aluminometasilicate). In further embodiments, the humectant is polysorbate 80 or SEPITRAP™ 80, or such as polysorbate 80, or such as SEPITRAP™ 80. In yet other embodiments, the humectant is polyoxyl hydrogenated castor oil, such as SEPITRAP™ 4000 (polyoxyl 40 hydrogenated castor oil and magnesium aluminosilicate).

[0030] In other embodiments, the spray-dried formulation is combined with one or more lubricants. Examples of lubricants include, but are not limited to, polyethylene glycol (PEG), magnesium stearate, sodium stearyl fumarate, stearic acid, sorbitan monostearate, sucrose monopalmitate, glyceryl monostearate, glyceryl tribehenate, glyceryl dibehenate, calcium stearate, zinc stearate, hydrous magnesium silicate, sodium oleate, sterotex, sodium benzoate, talc, sodium acetate, wax, sodium lauryl sulfate, or magnesium lauryl sulfate, or combinations thereof. In some embodiments, the lubricant is PEG, such as a PEG greater than about 6000 (e.g., PEG 6000, PEG 8000, PEG 20000, or PEG 35000). In other embodiments, the lubricant is magnesium stearate. In further embodiments, the lubricant is sodium stearyl fumarate. In yet other embodiments, the lubricant is stearic acid. In still further aspects, the lubricant is sorbitan monostearate. In other aspects, the lubricant is sucrose monopalmitate. In further aspects, the lubricant is glyceryl monostearate. In still other aspects, the lubricant is glyceryl tribehenate. In still further aspects, the lubricant is glyceryl dibehenate. In other aspects, the lubricant is calcium stearate. In still further aspects, the lubricant is zinc stearate. In still other aspects, the lubricant is hydrous magnesium silicate. In still further aspects, the lubricant is sodium oleate. In other aspects, the lubricant is sterotex. In still further aspects, the lubricant is sodium benzoate. In still other aspects, the lubricant is talc. In still further aspects, the lubricant is sodium acetate. In other aspects, the lubricant is a wax. In still further aspects, the lubricant is sodium lauryl sulfate. In still other aspects, the lubricant is magnesium lauryl sulfate. In yet a further aspect, the lubricant comprises PEG and a stearate, e.g., magnesium stearate. Two or more lubricants may be used in the external phase. In some embodiments, the external phase uses one lubricant.In other embodiments, the external phase uses two lubricants, hi further embodiments, the external phase uses three lubricants.

[0031] Formulations / Compositions The processes described herein provide useful products as described in the present disclosure. In certain embodiments, the present disclosure provides spray-dried formulations, i.e., granules, comprising fexofenadine zwitterion dihydrate and an inert matrix. Spray-dried formulations containing fexofenadine zwitterion dihydrate do not produce a bitter taste when contacted with the tongue of a human subject. The term "bitter taste", as used herein, refers to an unpleasant, sharp, tingling, and / or unpleasant taste that occurs when a substance contacts the taste buds or tongue of a subject. Additionally, the fexofenadine zwitterion products (formulations and compositions) defined herein may be chewed or swallowed. In some embodiments, chewing provides faster availability of fexofenadine for absorption compared to swallowing tablets, which must completely disintegrate before the fexofenadine can be absorbed. Thus, fexofenadine zwitterion may be formulated in both chewable and swallowable forms.

[0032] As discussed above, these spray dried formulations are in the form of granules and provide a stable medium for fexofenadine zwitterion dihydrate, i.e., fexofenadine zwitterion dihydrate remains in zwitterionic form in the granules and does not convert to fexofenadine hydrochloride or other fexofenadine salts when combined with other excipients. In some embodiments, fexofenadine zwitterion dihydrate remains in zwitterionic form in the granules when formulated as a solid dosage form. The term "inert matrix" as used herein refers to a solid form that provides a stable environment for the fexofenadine zwitterion dihydrate. In some embodiments, the inert matrix comprises one or more pharma- ceutically acceptable excipients. The one or more pharma-ceutically acceptable excipients are a diluent or a first disintegrant.

[0033] Examples of diluents include, but are not limited to, microcrystalline cellulose, mannitol, maltitol, sucrose, erythritol, dibasic calcium phosphate, tribasic calcium phosphate, isomalt, xylitol, maltodextrin, lactose, starch, sorbitol, sucrose, sucrose derivatives, inverted sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, cellulose derivatives, calcium carbonate, calcium lactate, calcium sulfate, or calcium phosphate, or combinations thereof. In some embodiments, the diluent is microcrystalline cellulose. In further embodiments, the diluent is microcrystalline cellulose having a pH of about 5 to about 7.5, e.g., 6.2. In other embodiments, the diluent is mannitol. In yet other embodiments, the diluent is mannitol having a pH of about 6 to about 7, e.g., 6.3. In further embodiments, the diluent is maltitol. In further embodiments, the diluent is maltitol having a pH of about 5 to about 7. In still other embodiments, the diluent is sucrose. In a further aspect, the diluent is sucrose at a pH of about 7. In yet a further aspect, the diluent is erythritol. In a further aspect, the diluent is erythritol at a pH of about 5 to about 7. In another aspect, the diluent is dicalcium phosphate. In a further aspect, the diluent is dicalcium phosphate at a pH of about 5.1 to about 7.3, such as about 7.3, or about 5.1, or about 6.1 to about 7.2. In a further aspect, the diluent is tricalcium phosphate. In a further aspect, the diluent is tricalcium phosphate at a pH of about 6.8. In yet another aspect, the diluent is isomalt. In a still further aspect, the diluent is xylitol. In another aspect, the diluent is maltodextrin. In a further aspect, the diluent is maltodextrin at a pH of about 4 to about 7. In a further aspect, the diluent is lactose. In yet another aspect, the diluent is starch. In further embodiments, the diluent is starch having a pH of about 4 to about 8. In still further aspects, the diluent is sorbitol. In further aspects, the diluent is sorbitol having a pH of about 4.5 to about 7. In further aspects, the diluent is a sucrose derivative. In yet other aspects, the diluent is inverted sucrose.In still further aspects, the diluent is lactitol. In still further aspects, the diluent is lactitol at a pH of about 4.5 to about 7. In other aspects, the diluent is erythritol. In still further aspects, the diluent is fructose. In still further aspects, the diluent is glucose. In still further aspects, the diluent is glucose at a pH of about 4 to about 6. In still further aspects, the diluent is calcium carbonate. In still further aspects, the diluent is calcium carbonate at a pH of about 9. In still further aspects, the diluent is cellulose. In still further aspects, the diluent is cellulose at a pH of about 5 to about 7.5. In still further aspects, the diluent is a cellulose derivative. In still further aspects, the diluent is calcium carbonate. In still further aspects, the diluent is calcium lactate. In still further aspects, the diluent is calcium sulfate. In still further aspects, the diluent is calcium phosphate.

[0034] Examples of the first disintegrant include croscarmellose sodium, sodium starch glycolate, crospovidone, pregelatinized starch, starch, hydroxypropyl cellulose (HPC), or combinations thereof. In some embodiments, the first disintegrant is croscarmellose sodium. In other embodiments, the first disintegrant is sodium starch glycolate. In further embodiments, the first disintegrant is crospovidone. In yet other embodiments, the first disintegrant is pregelatinized starch. In still further embodiments, the first disintegrant is starch. In other embodiments, the first disintegrant is hydroxypropyl cellulose (HPC). The spray dried formulation / granulation may be combined with additional excipients to provide the final fexofenadine zwitterion dihydrate composition, in some embodiments, the spray dried formulation further contains one or more of a wetting agent, an alkalizing agent, a buffering agent, a sweetening agent, a binder, or a solvent.

[0035] In other embodiments, the spray-dried formulation / granules further contain one or more wetting agents. Examples of wetting agents include, but are not limited to, poloxamers, polysorbates, or polyoxyl hydrogenated castor oil. In some embodiments, the wetting agent is a poloxamer, such as poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, or a combination thereof. In other embodiments, the wetting agent is a polysorbate, such as polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate), polysorbate 40 (polyoxyethylene (20) sorbitan monopalmitate), polysorbate 60 (polyoxyethylene (20) sorbitan monostearate), polysorbate 80 (polyoxyethylene (20) sorbitan monooleate), or SEPITRAP™ 80 (polysorbate 80 and magnesium aluminometasilicate). In further embodiments, the humectant is polysorbate 80 or SEPITRAP™ 80, or such as polysorbate 80, or such as SEPITRAP™ 80. In yet other embodiments, the humectant is polyoxyl hydrogenated castor oil, such as SEPITRAP™ 4000 (polyoxyl 40 hydrogenated castor oil and magnesium aluminosilicate).

[0036] In further embodiments, the spray-dried formulation / granules further contain one or more alkalizing agents. In certain aspects, the alkalizing agent is a strong base. In some aspects, the alkalizing agent is potassium hydroxide, calcium hydroxide, sodium hydroxide, or barium hydroxide, among others. In other aspects, the alkalizing agent is potassium hydroxide. In further aspects, the alkalizing agent is calcium hydroxide. In yet other aspects, the alkalizing agent is sodium hydroxide. In yet further aspects, the alkalizing agent is barium hydroxide. In yet other embodiments, the spray-dried formulation / granulation further contains one or more buffering agents. Examples of buffering agents include, but are not limited to, dibasic sodium phosphate 2H2O, monobasic sodium phosphate, citric acid / dibasic sodium phosphate, dibasic sodium phosphate hydrate, succinic acid / sodium hydroxide, citric acid / sodium citrate, sodium citrate hydrate, potassium citrate, maleic acid / sodium hydroxide, fumaric acid / sodium hydroxide, monobasic sodium phosphate hydrate, monobasic potassium phosphate / dibasic sodium phosphate hydrate, dibasic potassium phosphate, dibasic potassium phosphate hydrate. In some embodiments, the buffering agent is monobasic sodium phosphate, monobasic sodium phosphate hydrate, monobasic potassium phosphate / dibasic sodium phosphate, dibasic sodium phosphate hydrate, dibasic potassium phosphate, or dibasic potassium phosphate hydrate. In other embodiments, the buffering agent is monobasic sodium phosphate, monobasic sodium phosphate hydrate / dibasic sodium phosphate, or dibasic sodium phosphate hydrate, or combinations thereof. In further embodiments, the buffering agent is dibasic and monobasic phosphoric acid.

[0037] In yet further embodiments, the spray-dried formulation / granules further contain one or more sweeteners. Examples of sweeteners include sucralose, aspartame, acesulfame potassium, saccharin, steviol glycosides, neotame, advantame, sodium saccharin, sodium cyclamate, or ammonium glycyrrhizinate, or combinations thereof. In some aspects, the sweetener is sucralose. In other aspects, the sweetener is aspartame. In further aspects, the sweetener is acesulfame potassium. In still other aspects, the sweetener is saccharin. In still further aspects, the sweetener is steviol glycosides. In other aspects, the sweetener is neotame. In still further aspects, the sweetener is advantame. In still other aspects, the sweetener is sodium saccharin. In still further aspects, the sweetener is sodium cyclamate. In still further aspects, the sweetener is ammonium glycyrrhizinate.

[0038] In other embodiments, the spray-dried formulation / granulation further comprises one or more binders. Examples of binders include, but are not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), or carboxymethylcellulose (CMC), hydroxyethyl methylcellulose (HEMC), or hydroxyethyl cellulose (HEC), or combinations thereof. In some aspects, the binder is HPMC. In other aspects, the binder is HPMC having a viscosity of about 4 to about 100,000 mPa.s. In further aspects, the binder is HPMC 4 mPa.s or HPMC 5 mPa.s. In yet other aspects, the binder is HPC. In still further aspects, the binder is PVP. In other aspects, the binder is CMC. In further aspects, the binder is HEMC. In still other aspects, the binder is HEC. In further embodiments, the spray dried formulation / granulation further comprises one or more solvents. In some embodiments, the solvent is water. In other embodiments, the solvent is sterile water.

[0039] The spray-dried formulation / granulation may be combined with additional excipients to provide a final product comprising the disclosed fexofenadine zwitterionic composition. In some embodiments, the final fexofenadine zwitterionic composition further comprises one or more of a second disintegrant, a flavoring agent, and a lubricant. In some embodiments, the spray-dried formulation contains a second disintegrant. Examples of second disintegrants include sodium starch glycolate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or combinations thereof. In some aspects, the second disintegrant is sodium starch glycolate. In further aspects, the second disintegrant is crospovidone. In other aspects, the second disintegrant is pregelatinized starch. In still further aspects, the second disintegrant is starch. In other aspects, the second disintegrant is hydroxypropyl cellulose (HPC). In other embodiments, the final fexofenadine composition contains a flavoring agent.

[0040] In further embodiments, the final fexofenadine composition contains a lubricant. Examples of lubricants include, but are not limited to, polyethylene glycol (PEG), magnesium stearate, sodium stearyl fumarate, stearic acid, sorbitan monostearate, sucrose monopalmitate, glyceryl monostearate, glyceryl tribehenate, glyceryl dibehenate, calcium stearate, and zinc stearate, hydrous magnesium silicate, sodium oleate, sterotex, sodium benzoate, talc, sodium acetate, wax, sodium lauryl sulfate, or magnesium lauryl sulfate, or combinations thereof. In some aspects, the lubricant is PEG, e.g., PEG 6000. In other aspects, the lubricant is magnesium stearate. In further aspects, the lubricant is sodium stearyl fumarate. In yet other aspects, the lubricant is stearic acid. In still further aspects, the lubricant is sorbitan monostearate. In another aspect, the lubricant is sucrose monopalmitate. In a further aspect, the lubricant is glyceryl monostearate. In yet another aspect, the lubricant is glyceryl tribehenate. In yet a further aspect, the lubricant is glyceryl dibehenate. In another aspect, the lubricant is calcium stearate. In a further aspect, the lubricant is zinc stearate. In yet another aspect, the lubricant is hydrous magnesium silicate. In yet a further aspect, the lubricant is sodium oleate. In another aspect, the lubricant is STEROTEX. In a further aspect, the lubricant is sodium benzoate. In yet another aspect, the lubricant is talc. In yet a further aspect, the lubricant is sodium acetate. In another aspect, the lubricant is a wax. In a further aspect, the lubricant is sodium lauryl sulfate. In yet another aspect, the lubricant is magnesium lauryl sulfate. In yet a further embodiment, the lubricant comprises PEG and a stearate, such as magnesium stearate.

[0041] In certain aspects, the present disclosure provides a spray-dried formulation comprising fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a buffer, a sweetener, a binder, a diluent, a disintegrant, a flavoring agent, and a lubricant. In some embodiments, the spray-dried formulation contains two wetting agents. Examples of wetting agents include, but are not limited to, poloxamer, polysorbate, or polyoxyl hydrogenated castor oil. In some embodiments, the wetting agent is a poloxamer, such as poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, or a combination thereof. In other embodiments, the wetting agent is a polysorbate, such as polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate), polysorbate 40 (polyoxyethylene (20) sorbitan monopalmitate), polysorbate 60 (polyoxyethylene (20) sorbitan monostearate), polysorbate 80 (polyoxyethylene (20) sorbitan monooleate), or SEPITRAP™ 80 (polysorbate 80 and magnesium aluminometasilicate). In further embodiments, the wetting agent is polysorbate 80 or SEPITRAP™ 80, or such as polysorbate 80, or such as SEPITRAP™ 80. In yet other embodiments, the wetting agent is polyoxyl hydrogenated castor oil, such as SEPITRAP™ 4000 (polyoxyl 40 hydrogenated castor oil and magnesium aluminometasilicate). The spray-dried formulation may contain from about 0.5 to about 10% wt / wt of one or more wetting agents, hi some embodiments, the spray-dried formulation contains about 0.5, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10% wt / wt of one or more wetting agents.In other embodiments, the spray dried formulation is from about 0.5 to about 9, from about 0.5 to about 8, from about 0.5 to about 7, from about 0.5 to about 6, from about 0.5 to about 5, from about 0.5 to about 4, from about 0.5 to about 3, from about 0.5 to about 2, from about 0.5 to about 1, from about 1 to about 10, from about 1 to about 9, from about 1 to about 8, from about 1 to about 7, from about 1 to about 6, from about 1 to about 5, from about 1 to about 4, from about 1 to about 3, from about 1 to about 2, from about 2 to about 10, from about 2 to about 9, from about 2 to about 8, from about 2 to about 7, from about 2 to about 6, from about 2 to about 5, from about 2 to about 4, from about 2 to about 3, or about 9 to about 10% by weight / weight of one or more wetting agents.

[0042] In other embodiments, the spray-dried formulation contains an alkalizing agent. In certain aspects, the alkalizing agent is a strong base. In some aspects, the alkalizing agent is potassium hydroxide, calcium hydroxide, sodium hydroxide, or barium hydroxide, among others. In other aspects, the alkalizing agent is potassium hydroxide. In further aspects, the alkalizing agent is calcium hydroxide. In yet other aspects, the alkalizing agent is sodium hydroxide. In still further aspects, the alkalizing agent is barium hydroxide. The spray-dried formulation may contain about 0.5 to about 5% weight / weight of one or more alkalizing agents. In some embodiments, the spray-dried formulation contains about 0.5, about 1, about 1.5, about 2, about 2.5, about 3, about 3.5, about 4, about 4.5, or about 5% weight / weight of one or more alkalizing agents. In other embodiments, the spray dried formulation may be from about 0.5 to about 5, from about 0.5 to about 4.5, from about 0.5 to about 4, from about 0.5 to about 3.5, from about 0.5 to about 3, from about 0.5 to about 2.5, from about 0.5 to about 2, from about 0.5 to about 1.5, from about 0.5 to about 1, from about 1 to about 5, from about 1 to about 4.5, from about 1 to about 4, from about 1 to about 3.5, from about 1 to about 3, from about 1 to about 2.5, from about 1 to about 2, from about 1 to about 1.5, from about 1.5 to about 5, from about 1.5 to about 4.5, from about 1.5 to about 4, from about 1.5 to about 3.5, from about 1.5 to about 3, from about 1. or about 4.5 to about 5% mass / mass of one or more alkalizing agents.

[0043] In further embodiments, the spray-dried formulation contains one or two buffers. In some aspects, the spray-dried formulation contains one buffer. In other aspects, the spray-dried formulation contains two buffers. Examples of buffers include, but are not limited to, dibasic sodium phosphate 2H2O, monobasic sodium phosphate, citric acid / dibasic sodium phosphate, dibasic sodium phosphate hydrate, succinic acid / sodium hydroxide, citric acid / sodium citrate, sodium citrate hydrate, potassium citrate, maleic acid / sodium hydroxide, fumaric acid / sodium hydroxide, monobasic sodium phosphate hydrate, monobasic potassium phosphate / dibasic sodium phosphate hydrate, dibasic potassium phosphate, dibasic potassium phosphate hydrate. In some embodiments, the buffer is monobasic sodium phosphate, monobasic sodium phosphate hydrate, monobasic potassium phosphate / dibasic sodium phosphate, dibasic sodium phosphate hydrate, dibasic potassium phosphate, or dibasic potassium phosphate hydrate. In other embodiments, the buffer is monobasic sodium phosphate, monobasic sodium phosphate hydrate / dibasic sodium phosphate, or dibasic sodium phosphate hydrate, or combinations thereof. In further embodiments, the buffer is dibasic phosphate and monobasic phosphate. In some aspects, the buffer is sodium phosphate hydrate, such as dibasic sodium phosphate 2H2O, monobasic sodium phosphate, or a combination thereof. The spray-dried formulation contains about 0.2 to about 10% weight / weight of one or more buffers. In some embodiments, the spray-dried formulation contains about 0.2, about 0.5, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10% weight / weight of one or more buffers.In other embodiments, the spray dried formulation comprises from 0.2 to about 9, from about 0.2 to about 8, from about 0.2 to about 7, from about 0.2 to about 6, from about 0.2 to about 5, from about 0.2 to about 4, from about 0.2 to about 3, from about 0.2 to about 2, from about 0.2 to about 1, from about 0.5 to about 10, from about 0.5 to about 9, from about 0.5 to about 8, from about 0.5 to about 7, from about 0.5 to about 6, from about 0.5 to about 5, from about 0.5 to about 4, from about 0.5 to about 3, from about 0.5 to about 2, from about 0.5 to about 1, from about 1 to about 10, from about 1 to about 9, from about 1 to about 8, from about 1 to about 7, from about 1 to about 6, from about 1 to about 5, from about 1 to about 4, from about 1 to about 3, from about 1 to about 2, from about 2 to about 10 ... The composition contains one or more buffers at about 9, about 2 to about 8, about 2 to about 7, about 2 to about 6, about 2 to about 5, about 2 to about 4, about 2 to about 3, about 3 to about 10, about 3 to about 9, about 3 to about 8, about 3 to about 7, about 3 to about 6, about 3 to about 5, about 3 to about 4, about 4 to about 10, about 4 to about 9, about 4 to about 8, about 4 to about 7, about 4 to about 6, about 4 to about 5, about 5 to about 10, about 5 to about 9, about 5 to about 8, about 5 to about 7, about 5 to about 6, about 6 to about 10, about 6 to about 9, about 6 to about 8, about 6 to about 7, about 7 to about 10, about 7 to about 9, about 7 to about 8, about 8 to about 10, about 8 to about 9, or about 9 to about 10% by mass / mass.

[0044] Examples of sweeteners include sucralose, aspartame, acesulfame potassium, saccharin, steviol glycosides, neotame, advantame, sodium saccharin, sodium cyclamate, or ammonium glycyrrhizinate, or combinations thereof. In some embodiments, the sweetener is sucralose. In other embodiments, the sweetener is aspartame. In further embodiments, the sweetener is acesulfame potassium. In still other embodiments, the sweetener is saccharin. In still further embodiments, the sweetener is steviol glycosides. In other embodiments, the sweetener is neotame. In further embodiments, the sweetener is advantame. In still other embodiments, the sweetener is sodium saccharin. In still further embodiments, the sweetener is sodium cyclamate. The spray-dried formulation contains about 0.2 to about 3% weight / weight of one or more sweeteners. In some embodiments, the spray-dried formulation contains about 0.2, about 0.5, about 0.75, about 1, about 1.25, about 1.5, about 1.75, about 2, about 2.25, about 2.5, about 2.75, or about 3% weight / weight of one or more sweeteners. In other aspects, the spray-dried formulation contains 0.2 to about 2.5, about 0.2 to about 2, about 0.2 to about 1.5, about 0.2 to about 1, about 0.2 to about 0.5, about 0.5 to about 3, about 0.5 to about 2.5, about 0.5 to about 2, about 0.5 to about 1.5, about 0.5 to about 1, about 1 to about 3, about 1 to about 2.5, about 1 to about 2, about 1 to about 1.5, about 1.5 to about 3, about 1.5 to about 2.5, about 1.5 to about 2, about 2 to about 3, about 2 to about 2.5, or about 2.5 to about 3% w / w of one or more sweeteners.

[0045] In yet other embodiments, the spray-dried formulation contains a binder. Examples of binders include, but are not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), or carboxymethylcellulose (CMC), hydroxyethyl methylcellulose (HEMC), or hydroxyethyl cellulose (HEC), or combinations thereof. In some aspects, the binder is HPMC. In other aspects, the binder is HPMC having a viscosity of about 4 to about 100,000 mPa.s. In further aspects, the binder is HPMC 4 mPa.s or HPMC 5 mPa.s. In still other aspects, the binder is HPC. In still further aspects, the binder is PVP. In other aspects, the binder is CMC. In further aspects, the binder is HEMC. In still other aspects, the binder is HEC. The spray-dried formulation may contain about 0.5 to about 5% weight / weight of one or more binders. In some embodiments, the spray dried formulation contains about 0.5, about 1, about 2, about 3, about 4, or about 5% weight / weight of one or more binders. In other embodiments, the spray dried formulation contains about 0.5 to about 5, about 0.5 to about 4, about 0.5 to about 3, about 0.5 to about 2, about 0.5 to about 1, about 1 to about 5, about 1 to about 4, about 1 to about 3, about 1 to about 2, about 2 to about 5, about 2 to about 4, about 2 to about 3, about 3 to about 5, about 3 to about 4, or about 4 to about 5% weight / weight of one or more binders.

[0046] In still further embodiments, the spray-dried formulation contains one or more diluents. In some aspects, the spray-dried formulation contains one, two, three, four, five, or six diluents. In other aspects, the spray-dried formulation contains two diluents. In further aspects, the spray-dried formulation contains three diluents. In yet other aspects, the spray-dried formulation contains four diluents. In still further aspects, the spray-dried formulation contains five diluents. In other aspects, the spray-dried formulation contains six diluents. Examples of diluents include, but are not limited to, microcrystalline cellulose, mannitol, maltitol, sucrose, erythritol, dibasic calcium phosphate, tribasic calcium phosphate, isomalt, xylitol, maltodextrin, lactose, starch, sorbitol, sucrose, sucrose derivatives, invert sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, cellulose derivatives, calcium carbonate, calcium lactate, calcium sulfate, or calcium phosphate, or combinations thereof. In certain embodiments, the diluent is microcrystalline cellulose. In further embodiments, the diluent is microcrystalline cellulose at a pH of about 5 to about 7.5, e.g., 6.2. In other embodiments, the diluent is mannitol. In yet other embodiments, the diluent is mannitol at a pH of about 6 to about 7, e.g., 6.3. In further embodiments, the diluent is maltitol. In further embodiments, the diluent is maltitol at a pH of about 5 to about 7. In yet other embodiments, the diluent is sucrose. In further embodiments, the diluent is sucrose at a pH of about 7. In still further embodiments, the diluent is erythritol. In further embodiments, the diluent is erythritol at a pH of about 5 to about 7. In other embodiments, the diluent is dicalcium phosphate. In further embodiments, the diluent is dicalcium phosphate at a pH of about 5.1 to about 7.3, e.g., about 7.3, or about 5.1, or about 6.1 to about 7.2. In further embodiments, the diluent is tricalcium phosphate. In a further embodiment, the diluent is tricalcium phosphate with a pH of about 6.8. In yet another embodiment, the diluent is isomalt. In yet a further embodiment, the diluent is xylitol. In another embodiment, the diluent is maltodextrin.In a further aspect, the diluent is maltodextrin having a pH of about 4 to about 7. In a further aspect, the diluent is lactose. In yet another aspect, the diluent is starch. In a further embodiment, the diluent is starch having a pH of about 4 to about 8. In still a further aspect, the diluent is sorbitol. In a further aspect, the diluent is sorbitol having a pH of about 4.5 to about 7. In a further aspect, the diluent is a sucrose derivative. In a still further aspect, the diluent is inverted sucrose. In a still further aspect, the diluent is lactitol. In a further aspect, the diluent is lactitol having a pH of about 4.5 to about 7. In another aspect, the diluent is erythritol. In a further aspect, the diluent is erythritol having a pH of about 5 to about 7. In a further aspect, the diluent is fructose. In a still further aspect, the diluent is glucose. In a further aspect, the diluent is glucose having a pH of about 4 to about 6. In still further aspects, the diluent is calcium carbonate. In further aspects, the diluent is calcium carbonate with a pH of about 9. In other aspects, the diluent is cellulose. In further aspects, the diluent is cellulose with a pH of about 5 to about 7.5. In further aspects, the diluent is a cellulose derivative. In still other aspects, the diluent is calcium carbonate. In still further aspects, the diluent is calcium lactate. In other aspects, the diluent is calcium sulfate. In further aspects, the diluent is calcium phosphate. The spray-dried formulation may contain about 30 to about 80% weight / weight of one or more diluents. In some aspects, the spray-dried formulation contains about 30, about 40, about 50, about 60, about 70, or about 80% weight / weight of one or more diluents. In other aspects, the spray-dried formulation contains about 30 to about 70, about 30 to about 60, about 30 to about 50, about 30 to about 40, about 40 to about 80, about 40 to about 70, about 40 to about 60, about 40 to about 50, about 50 to about 80, about 50 to about 70, about 50 to about 60, about 60 to about 80, about 60 to about 70, or about 70 to about 80% w / w of one or more diluents.

[0047] In further embodiments, the spray-dried formulation contains one or more disintegrants. In some aspects, the spray-dried formulation contains two disintegrants. In other aspects, the spray-dried formulation contains three disintegrants. Examples of disintegrants include, but are not limited to, croscarmellose sodium, sodium starch glycolate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or combinations thereof. In some aspects, the disintegrant is croscarmellose sodium. In other aspects, the disintegrant is sodium starch glycolate. In further aspects, the disintegrant is crospovidone. In yet other aspects, the disintegrant is pregelatinized starch. In still further aspects, the disintegrant is starch. In other aspects, the disintegrant is hydroxypropyl cellulose (HPC). The spray-dried formulation may contain about 3 to about 15% weight / weight of one or more disintegrants. In certain embodiments, the spray dried formulation contains about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, or about 15% weight / weight of one or more disintegrants.In other embodiments, the spray dried formulation is from about 3 to about 14, from about 3 to about 13, from about 3 to about 12, from about 3 to about 11, from about 3 to about 10, from about 3 to about 9, from about 3 to about 8, from about 3 to about 7, from about 3 to about 6, from about 3 to about 5, from about 3 to about 4, from about 4 to about 15, from about 4 to about 14, from about 4 to about 13, from about 4 to about 12, from about 4 to about 11, from about 4 to about 10, from about 4 to about 9, from about 4 to about 8, from about 4 ~ about 7, about 4 to about 6, about 4 to about 5, about 5 to about 15, about 5 to about 14, about 5 to about 13, about 5 to about 12, about 5 to about 11, about 5 to about 10, about 5 to about 9, about 5 to about 8, about 5 to about 7, about 5 to about 6, about 6 to about 15, about 6 to about 14, about 6 to about 13, about 6 to about 12, about 6 to about 11, about 6 to about 10, about 6 to about 9, about 6 to about 8, about 6 to about 7, about 7 to about 15, about 7 to about 14, about 7 to about 13, about 7 to about 12, about 7 to about 11, about 7 to about 10, about 7 to about 9, about 7 to about 8, about 8 to about 15, about 8 to about 14, about 8 to about 13, about 8 to about 12, about 8 to about 11, about 8 to about 10, about 8 to about 9, about 9 to about 15, about 9 to about 14, about 9 to about 13, about 9 to about 12, about 9 to about 11, about 9 to about 1 or about 14 to about 15% mass / mass of one or more disintegrants.

[0048] In yet other embodiments, the spray-dried formulation contains one or more lubricants. In some aspects, the spray-dried formulation contains two lubricants. Examples of lubricants include, but are not limited to, polyethylene glycol (PEG), magnesium stearate, sodium stearyl fumarate, stearic acid, sorbitan monostearate, sucrose monopalmitate, glyceryl monostearate, glyceryl tribehenate, glyceryl dibehenate, calcium stearate, and zinc stearate, hydrous magnesium silicate, sodium oleate, sterotex, sodium benzoate, talc, sodium acetate, wax, sodium lauryl sulfate, or magnesium lauryl sulfate, or combinations thereof. In some aspects, the lubricant is PEG, such as PEG 6000. In other aspects, the lubricant is magnesium stearate. In further aspects, the lubricant is sodium stearyl fumarate. In yet other aspects, the lubricant is stearic acid. In still further aspects, the lubricant is sorbitan monostearate. In other aspects, the lubricant is sucrose monopalmitate. In further aspects, the lubricant is glyceryl monostearate. In still other aspects, the lubricant is glyceryl tribehenate. In still further aspects, the lubricant is glyceryl dibehenate. In other aspects, the lubricant is calcium stearate. In still further aspects, the lubricant is zinc stearate. In still other aspects, the lubricant is hydrous magnesium silicate. In still further aspects, the lubricant is sodium oleate. In other aspects, the lubricant is sterotex. In still further aspects, the lubricant is sodium benzoate. In still other aspects, the lubricant is talc. In still further aspects, the lubricant is sodium acetate. In other aspects, the lubricant is a wax. In still further aspects, the lubricant is sodium lauryl sulfate. In still other aspects, the lubricant is magnesium lauryl sulfate. In still further embodiments, the lubricant comprises PEG and a stearate, e.g., magnesium stearate. The spray-dried formulation may contain from about 0.5 to about 10% weight / weight of one or more lubricants.In some embodiments, the spray dried formulation contains about 0.5, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10% w / w of one or more lubricants. In other embodiments, the spray dried formulation contains about 0.5 to about 9, about 0.5 to about 8, about 0.5 to about 7, about 0.5 to about 6, about 0.5 to about 5, about 0.5 to about 4, about 0.5 to about 3, about 0.5 to about 2, about 0.5 to about 1, 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 2 to about 10, about 2 to about 9, about 2 to about 8, about 2 to about 7, about 2 to about 6, about 2 to about 5, about 2 to about 4, about 2 to about 3, about about 3 to about 10, about 3 to about 9, about 3 to about 8, about 3 to about 7, about 3 to about 6, about 3 to about 5, about 3 to about 4, about 4 to about 10, about 4 to about 9, about 4 to about 8, about 4 to about 7, about 4 to about 6, about 4 to about 5, about 5 to about 10, about 5 to about 9, about 5 to about 8, about 5 to about 7, about 5 to about 6, about 6 to about 10, about 6 to about 9, about 6 to about 8, about 6 to about 7, about 7 to about 10, about 7 to about 9, about 7 to about 8, about 8 to about 10, about 8 to about 9, or about 9 to about 10% by mass / mass of one or more lubricants.

[0049] In still further embodiments, the spray-dried formulation may contain one or more flavoring agents. Examples of flavoring agents include agents having grape or mint flavors. The spray-dried formulation may contain about 0.1 to about 5% w / w of one or more flavoring agents. In some aspects, the spray-dried formulation contains about 0.5, about 1, about 2, about 3, about 4, or about 5% w / w of one or more flavoring agents. In other aspects, the spray-dried formulation contains about 0.5 to about 5, about 0.5 to about 4, about 0.5 to about 3, about 0.5 to about 2, about 0.5 to about 1, about 1 to about 5, about 1 to about 4, about 1 to about 3, about 1 to about 2, about 2 to about 5, about 2 to about 4, about 2 to about 3, about 3 to about 5, about 3 to about 4, or about 4 to about 5% w / w of one or more flavoring agents.

[0050] In other embodiments, the spray dried formulation contains fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a first disintegrant, a second disintegrant, a flavoring agent, and a lubricant. In a further embodiment, the spray dried formulation contains fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a first disintegrant, a second disintegrant, a first lubricant, a second lubricant, and a flavoring agent. In yet other embodiments, the spray dried formulation contains fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a first disintegrant, a second disintegrant, a flavoring agent, and a lubricant. In yet a further embodiment, the spray dried formulation contains fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, and a lubricant.

[0051] In other embodiments, the spray dried formulation contains fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, and a lubricant. In a further embodiment, the spray dried formulation contains fexofenadine zwitterion dihydrate, a first wetting agent, a second wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, and a lubricant. In yet another embodiment, the spray dried formulation contains fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a fourth diluent, a fifth diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, and a lubricant.

[0052] In still a further embodiment, the spray dried formulation contains fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a fourth diluent, a fifth diluent, a sixth diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, and a lubricant. In other embodiments, the spray dried formulation contains fexofenadine zwitterion dihydrate, a first wetting agent, a second wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, a first lubricant, and a second lubricant. In a further embodiment, the spray dried formulation contains fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, a first lubricant, and a second lubricant.

[0053] As noted, the spray-dried formulation may also contain water. In some embodiments, the water is sterile water. The present disclosure also provides an oral solid dosage form comprising the spray dried formulation / granule or the final fexofenadine zwitterionic composition as described herein. Examples of oral solid dosage forms include tablets, caplets, or dispersible granules. In some aspects, the oral solid dosage form is a tablet, such as an orally disintegrating tablet or a chewable tablet. In other aspects, the oral solid dosage form is a caplet, such as an orally disintegrating caplet or a chewable caplet. In further aspects, the oral solid dosage form is a dispersible granule. Desirably, the oral solid dosage form lacks a coating layer for bitterness masking. In some embodiments, the oral dosage form lacks a coating layer containing a eutaglyte polymer. The term "chewable" as used herein refers to a dosage form that is intended to be chewed and then swallowed by a subject, rather than swallowed whole. In some embodiments, the subject chews the chewable dosage form, thereby breaking the dosage form into finer particles with a larger surface area. Without wishing to be bound by any particular theory, this greater surface area allows the fexofenadine zwitterion to be absorbed more rapidly as compared to a non-chewed dosage form. In another embodiment, the dosage form is an orally disintegrating tablet that dissolves when held in the subject's mouth. In a further embodiment, the patient chews the dosage form to cause it to dissolve. In yet another embodiment, the patient swallows the dosage form.

[0054] The oral solid dosage form may contain an amount of fexofenadine zwitterion dihydrate determined by one of skill in the art. In some embodiments, the oral dosage form contains about 10 to about 200 mg of fexofenadine zwitterion dihydrate. In some embodiments, the oral dosage form contains about 10, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120, about 130, about 140, about 150, about 160, about 170, about 180, about 190, or about 200 mg of fexofenadine zwitterion dihydrate.In other embodiments, the oral dosage form is from about 10 to about 180, from about 10 to about 160, from about 10 to about 140, from about 10 to about 120, from about 10 to about 100, from about 10 to about 80, from about 10 to about 60, from about 10 to about 40, from about 20 to about 200, from about 20 to about 180, from about 20 to about 160, from about 20 to about 140, from about 20 to about 120, from about 20 to about 100, from about 20 to about 80, from about 20 to about 60, from about 20 to about 40, from about 30 to about 200, from about 30 to about 180, from about 30 to about 160, from about 30 to about 140, from about 30 to about 120, from about 30 to about about 100, about 30 to about 80, about 30 to about 60, about 40 to about 200, about 40 to about 180, about 40 to about 160, about 40 to about 140, about 40 to about 120, about 40 to about 100, about 40 to about 80, about 40 to about 60, about 50 to about 200, about 50 to about 180, about 50 to about 160, about 50 to about 140, about 50 to about 120, about 50 to about 100, about 50 to about 80, about 60 to about 200, about 60 to about 180, about 60 to about 160, about 60 to about 140, about 60 to about 120, about 60 to about 100, about 60 to about 80, about 70 to about 200, about 70 to about 180, about 70 to about 160, about 70 to about 140, about 70 to about 120, about 70 to about 100, about 80 to about 200, about 80 to about 180, about 80 to about 160, about 80 to about 140, about 80 to about 120, about 80 to about 100, about 90 to about 200, about 90 to about 180, about 90 to about 160, about 90 to about 140, about 90 to about 120, about 100 to about 200, about 100 to about 180, about 100 to about 160, about 100 to about 140, about 100 to about 120, about 110 to about about 200, about 110 to about 180, about 110 to about 160, about 110 to about 140, about 120 to about 200, about 120 to about 180, about 120 to about 160, about 120 to about 140, about 130 to about 200, about 130 to about 180, about 130 to about 160, about 140 to about 200, about 140 to about 180, about 140 to about 160, about 150 to about 200, about 150 to about 170, about 160 to about 200, about 160 to about 180, about 170 to about 200, about 180 to about 200, or about 190 to about 200. In a further embodiment, the spray dried formulation contains about 30 to about 180 mg of fexofenadine zwitterion dihydrate. In yet another embodiment, the spray dried formulation contains about 30 mg of fexofenadine zwitterion dihydrate. In yet a further embodiment, the spray dried formulation contains about 60 mg of fexofenadine zwitterion dihydrate.In another embodiment, the spray dried formulation contains about 120 mg of fexofenadine zwitterion dihydrate. In a further embodiment, the spray dried formulation contains about 180 mg of fexofenadine zwitterion dihydrate.

[0055] method The spray-dried compositions and oral solid dosage forms described herein are useful for alleviating allergy symptoms in a patient in need thereof. The methods include administering to the patient a therapeutically effective amount of the spray-dried formulation or oral solid dosage form. One of ordinary skill in the art would be able to determine suitable allergies that may be treated using the described compositions and dosage forms. For example, the allergy may be due to indoor or outdoor allergens. In some embodiments, the allergy is due to one or more indoor allergens. A variety of indoor allergens are known, including dust mites, pet allergens, or mold. In further embodiments, the allergy is due to dust mites. In other embodiments, the allergy is due to pet allergens, such as animal saliva, animal urine, or animal dander. In still further embodiments, the allergy is due to indoor mold. In yet other embodiments, the allergy is due to one or more outdoor allergens. Many outdoor allergies are known in part, including, but not limited to, pollen and mold. In some embodiments, the outdoor allergy is pollen, such as from grasses, weeds, or trees. In other embodiments, the outdoor allergy is from outdoor mold.

[0056] As a result of allergies, a patient may experience a variety of symptoms. For example, a patient may experience one or more of the following: red eyes, itchy eyes, watery eyes, itchy nose, runny nose, stuffy nose, sneezing, stuffy nose, wheezing, coughing, chest tightness, facial pain, rash, hives, shortness of breath, coughing, postnasal drip, itchy throat, dry skin, sinus pressure, decreased sense of smell, decreased sense of taste, or decreased quality of sleep. In some embodiments, the symptom is red eyes. In other embodiments, the symptom is itchy eyes. In further embodiments, the symptom is watery eyes. In still other embodiments, the symptom is itchy nose. In still further embodiments, the symptom is runny nose. In other embodiments, the symptom is stuffy nose. In still further embodiments, the symptom is sneezing. In still other embodiments, the symptom is stuffy nose. In still further embodiments, the symptom is wheezing. In other embodiments, the symptom is coughing. In still further embodiments, the symptom is chest tightness. In still other embodiments, the symptom is facial pain. In still further embodiments, the symptom is a rash. In other embodiments, the symptom is hives. In further embodiments, the symptom is shortness of breath. In still other embodiments, the symptom is a cough. In still further embodiments, the symptom is postnasal drip. In other embodiments, the symptom is an itchy throat. In further embodiments, the symptom is dry skin. In still other embodiments, the symptom is sinus pressure. In still further embodiments, the symptom is a decreased sense of smell. In other embodiments, the symptom is a decreased sense of taste. In further embodiments, the symptom is a decreased quality of sleep. Thus, the methods described herein are useful for treating these symptoms. In some embodiments, the methods ameliorate one or more, or all, of the symptoms. In other embodiments, the methods reduce the number of symptoms in a patient. In further embodiments, the methods prevent the onset of one or more symptoms in a patient.

[0057] Thus, these compositions and dosage forms are useful for relieving symptoms of upper respiratory tract allergies in a patient in need thereof. These methods include administering to a patient a therapeutically effective amount of the spray-dried formulation or oral solid formulation described herein. In some embodiments, the symptoms are runny nose, itchy, watery eyes, sneezing, itchy nose, itchy throat, or a combination thereof. In further embodiments, the upper respiratory tract allergy is hay fever. The following examples are provided to illustrate some of the concepts described within this disclosure. Each example is considered to provide a particular individual embodiment of the compositions, methods of preparation, and uses, but no example should be considered to limit the more general embodiments described herein. In the following examples, efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperatures, etc.) but some experimental error and deviation should be accounted for. Unless otherwise noted, temperatures are in °C and pressures are at or near atmospheric.

[0058] Aspects Aspect 1: A method for preparing a spray-dried formulation comprising fexofenadine zwitterion dihydrate comprising spray drying (i) a fexofenadine zwitterion dihydrate composition and (ii) an inert matrix. Aspect 2. The process of aspect 1, wherein the inert matrix comprises one or more pharma- ceutically acceptable excipients. Aspect 3: The process of aspect 1 or 2, wherein the pharma- ceutically acceptable excipient is a diluent, binder, glidant, or disintegrant, or a combination thereof. Aspect 4: The process of aspect 3, wherein the diluent is microcrystalline cellulose, mannitol, maltitol, sucrose, erythritol, dibasic calcium phosphate, tribasic calcium phosphate, isomalt, xylitol, maltodextrin, lactose, starch, sorbitol, sucrose, sucrose derivatives, inverted sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, cellulose derivatives, calcium carbonate, calcium lactate, calcium sulfate, or calcium phosphate, or a combination thereof.

[0059] Aspect 5: The process of aspect 4, wherein the pH of the microcrystalline cellulose is between pH 5 and 7.5, preferably 6.2. Aspect 6: The process of aspect 4, wherein the mannitol has a pH of about 6 to about 7, preferably 6.3. Aspect 7. The process of aspect 3, wherein the disintegrant is croscarmellose sodium, sodium starch glycolate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or a combination thereof.

[0023] Aspect 8: The process of any one of aspects 1-7, carried out using a fluidized bed and spraying system, such as tangential spray, top spray, or bottom spray.

[0060] Aspect 9: (a) combining fexofenadine hydrochloride, water, and a wetting agent; (b) combining the product of step (a) with an alkalizing agent; (c) adjusting the pH of the product of step (b) to pH 5.8-7 with one or more buffering agents; (d) combining the product of step (c) with a sweetening agent; (e) combining the product of step (d) with a binder. further comprising; The pH of the fexofenadine zwitterion dihydrate composition is 6.5 to 7, preferably 6.7. The process according to any one of aspects 1 to 8. Embodiment 10: The process of embodiment 9, wherein fexofenadine hydrochloride is combined with a solution comprising water and a wetting agent. Embodiment 11: The process of embodiment 9 or 10, carried out using a vessel comprising a rotor-stator homogenizer. Embodiment 12: The process of any one of embodiments 9 to 11, further comprising combining the spray-dried formulation with one or more of a second portion of a disintegrant, a second disintegrant, a second portion of a diluent, a flavoring agent, a second portion of a wetting agent, and one or more lubricants.

[0061] Aspect 13: The process of aspect 12, wherein the second disintegrant is sodium starch glycolate, crospovidone, pregelatinized starch, starch, hydroxypropyl cellulose (HPC), or a combination thereof. Aspect 14: The process of aspect 12 or 13, wherein the lubricant is polyethylene glycol (PEG) such as PEG 6000, magnesium stearate, sodium stearyl fumarate, stearic acid, sorbitan monostearate, sucrose monopalmitate, glyceryl monostearate, glyceryl tribehenate, glyceryl dibehenate, calcium stearate, and zinc stearate, hydrous magnesium silicate, sodium oleate, Sterotex, sodium benzoate, talc, sodium acetate, wax, sodium lauryl sulfate, or magnesium lauryl sulfate, or a combination thereof. Embodiment 15: A product prepared according to the process of any one of embodiments 1 to 14. Embodiment 16: A spray-dried formulation comprising fexofenadine zwitterion dihydrate and an inert matrix.

[0062] Embodiment 17: The spray-dried formulation of embodiment 16, wherein the inert matrix comprises one or more pharma- ceutically acceptable excipients. Embodiment 18: The spray-dried formulation of embodiment 17, wherein the one or more pharma- ceutical acceptable excipients are a diluent or a first disintegrant. Aspect 19: The spray dried formulation of aspect 18, wherein the diluent is microcrystalline cellulose, mannitol, isomalt, xylitol, or a combination thereof, preferably microcrystalline cellulose and mannitol, preferably microcrystalline cellulose, mannitol, maltitol, maltodextrin, lactose, starch, sorbitol, sucrose, sucrose derivatives, inverted sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, cellulose derivatives, calcium carbonate, calcium lactate, calcium sulfate, or calcium phosphate, or a combination thereof. Aspect 20. The spray-dried formulation of aspect 19, wherein the microcrystalline cellulose has a pH of 5 to 7.5, preferably 6.2.

[0063] Aspect 21: The spray-dried formulation of Aspect 19, wherein the mannitol has a pH of about 6 to about 7, preferably 6.3. Aspect 22: The spray-dried formulation of Aspect 18, wherein the first disintegrant is croscarmellose sodium, sodium starch glycolate, crospovidone, pregelatinized starch, starch, hydroxypropyl cellulose (HPC), or a combination thereof. Embodiment 23: The spray-dried formulation of any one of embodiments 16-22, further comprising one or more of a humectant, an alkalizing agent, a buffering agent, a sweetening agent, a binder, or a solvent. Aspect 24. The spray-dried formulation of aspect 23, wherein the wetting agent comprises a poloxamer, such as poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, or a combination thereof.

[0064] Aspect 25. The spray-dried formulation of aspect 23 or 24, wherein the alkalizing agent is a strong base such as potassium hydroxide, calcium hydroxide, sodium hydroxide, or barium hydroxide. Aspect 26: The spray dried formulation of any one of aspects 23-25, wherein the buffer is sodium phosphate dibasic 2H2O, sodium phosphate monobasic, citric acid / sodium phosphate dibasic, sodium phosphate dibasic hydrate, succinic acid / sodium hydroxide, citric acid / sodium citrate, sodium citrate hydrate, potassium citrate, maleic acid / sodium hydroxide, fumaric acid / sodium hydroxide, sodium phosphate monobasic hydrate, potassium phosphate monobasic / sodium phosphate dibasic, sodium phosphate dibasic hydrate, potassium phosphate dibasic, potassium phosphate dibasic hydrate, or preferably sodium phosphate monobasic, sodium phosphate monobasic hydrate, potassium phosphate monobasic / sodium phosphate dibasic, sodium phosphate dibasic hydrate, potassium phosphate dibasic, or more preferably sodium phosphate monobasic, sodium phosphate monobasic / sodium phosphate dibasic, or sodium phosphate dibasic hydrate, or a combination thereof, or preferably dibasic and monobasic.

[0065] Aspect 27: The spray-dried formulation of any one of Aspects 23-26, wherein the sweetening agent is sucralose, aspartame, acesulfame potassium, saccharin, steviol glycosides, neotame, advantame, sodium saccharin, sodium cyclamate, or ammonium glycyrrhizinate, or a combination thereof. Embodiment 28: The spray dried formulation of any one of embodiments 23 to 27, wherein the binder is hydroxypropyl methylcellulose (HPMC), such as HPMC 4 mPa.s or HPMC 5 mPa.s, hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), or carboxymethyl cellulose (CMC), hydroxyethyl methylcellulose (HEMC), or hydroxyethyl cellulose (HEC), or a combination thereof. Embodiment 29: The spray-dried formulation of any one of embodiments 23-28, wherein the solvent is water. Embodiment 30: The spray-dried formulation of any one of embodiments 23-29, further comprising one or more of a second disintegrant, a flavoring agent, and a lubricant.

[0066] Aspect 31: The spray-dried formulation of aspect 30, wherein the second disintegrant is sodium starch glycolate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or a combination thereof. Embodiment 32: The spray-dried formulation of embodiment 30 or 31, wherein the lubricant is polyethylene glycol, such as polyethylene glycol 6000, magnesium stearate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or a combination thereof. Embodiment 33: The spray dried formulation of any one of embodiments 16 to 32, which does not produce a bitter taste upon contact with the tongue of a human subject. Aspect 34: Fexofenadine zwitterion dihydrate; Wetting agent; Alkalizing agents; Buffers; Sweeteners; Binder; Diluent; Disintegrants; Flavoring agents; and lubricant 20. A spray-dried formulation comprising:

[0067] Embodiment 35: The spray-dried formulation of embodiment 34, comprising two wetting agents. Embodiment 36: The spray-dried formulation of embodiment 34 or 35, wherein the wetting agent comprises a poloxamer, such as Poloxamer 188, Poloxamer 407, Poloxamer 237, Poloxamer 338, a polysorbate, such as Polysorbate 80 or SEPITRAP™ 80, or a polyoxyl hydrogenated castor oil, such as SEPITRAP™ 4000, or a combination thereof. Embodiment 37: The spray-dried formulation of any one of embodiments 34-36, comprising about 0.5 to about 10% weight / weight of a humectant. Embodiment 38: The spray-dried formulation of any one of embodiments 34-37, wherein the alkalizing agent is sodium hydroxide. Embodiment 39: The spray-dried formulation of any one of embodiments 34 to 38, comprising about 0.5 to about 5% weight / weight of an alkalizing agent.

[0068] Embodiment 40: The spray-dried formulation of any one of embodiments 34 to 39, comprising two buffering agents. Aspect 41: The spray dried formulation of any one of aspects 34-40, wherein the buffer is sodium phosphate dibasic 2H2O, sodium phosphate monobasic, citric acid / sodium phosphate dibasic, sodium phosphate dibasic hydrate, succinic acid / sodium hydroxide, citric acid / sodium citrate, sodium citrate hydrate, potassium citrate, maleic acid / sodium hydroxide, fumaric acid / sodium hydroxide, sodium phosphate monobasic hydrate, potassium phosphate monobasic / sodium phosphate dibasic, sodium phosphate dibasic hydrate, potassium phosphate dibasic, potassium phosphate dibasic hydrate, or preferably sodium phosphate monobasic, sodium phosphate monobasic hydrate, potassium phosphate monobasic / sodium phosphate dibasic, sodium phosphate dibasic hydrate, potassium phosphate dibasic, or more preferably sodium phosphate monobasic, sodium phosphate monobasic / sodium phosphate dibasic, or sodium phosphate dibasic hydrate, or a combination thereof, or preferably dibasic and monobasic.

[0069] Embodiment 42: The spray-dried formulation of any one of embodiments 34 to 41, comprising about 0.2 to about 10% weight / weight of a buffer. Aspect 43: The spray-dried formulation of any one of Aspects 34 to 42, wherein the sweetening agent is sucralose, aspartame, acesulfame potassium, saccharin, steviol glycosides, neotame, advantame, sodium saccharin, sodium cyclamate, or ammonium glycyrrhizinate, or a combination thereof. Embodiment 44: The spray-dried formulation of any one of embodiments 34 to 43, comprising about 0.2 to about 3% weight / weight of a sweetener. Aspect 45: The spray dried formulation of any one of aspects 34 to 44, wherein the binder is hydroxypropyl methylcellulose (HPMC), such as HPMC 4 mPa.s or HPMC 5 mPa.s, hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), or carboxymethyl cellulose (CMC), hydroxyethyl methylcellulose (HEMC), or hydroxyethyl cellulose (HEC), or a combination thereof. Embodiment 46: The spray-dried formulation of any one of embodiments 34 to 45, comprising about 0.5 to about 5% weight / weight of a binder. Embodiment 47: The spray-dried formulation of any one of embodiments 34 to 46, comprising one, two, three, four, or five diluents. Aspect 48: The spray dried formulation of any one of aspects 34 to 47, wherein the diluent is microcrystalline cellulose, mannitol, isomalt, xylitol, maltitol, maltodextrin, lactose, starch, sorbitol, sucrose, sucrose derivatives, inverted sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, cellulose derivatives, calcium carbonate, calcium lactate, calcium sulfate, or calcium phosphate, or a combination thereof, preferably microcrystalline cellulose and mannitol. Embodiment 49: The spray-dried formulation of any one of embodiments 34 to 48, comprising about 30 to about 80% weight / weight of a diluent.

[0070] Embodiment 50: The spray-dried formulation of embodiment 48, wherein the microcrystalline cellulose has a pH of from pH 5 to 7.5, preferably 6.2. Embodiment 51: The spray-dried formulation of embodiment 48, wherein the mannitol has a pH of about 6 to about 7, or such as 6.3. Embodiment 52: The spray-dried formulation of any one of embodiments 34 to 50, comprising one, two, or three disintegrants. Aspect 53: The spray-dried formulation of any one of Aspects 34 to 52, wherein the disintegrant is croscarmellose sodium, sodium starch glycolate, sodium starch glycolate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or a combination thereof, or a combination thereof.

[0071] Embodiment 54: The spray-dried formulation of any one of 34 to 53, comprising about 3 to about 15% weight / weight of a disintegrant. Embodiment 55: The spray-dried formulation of any one of embodiments 34 to 54, comprising one or two lubricants. Aspect 56: The spray-dried formulation of any one of Aspects 34 to 55, wherein the lubricant is polyethylene glycol, such as polyethylene glycol 6000, magnesium stearate, sodium stearyl fumarate, stearic acid, sorbitan monostearate, sucrose monopalmitate, glyceryl monostearate, glyceryl tribehenate, glyceryl dibehenate, calcium stearate, and zinc stearate, hydrous magnesium silicate, sodium oleate, Sterotex, sodium benzoate, talc, sodium acetate, wax, sodium lauryl sulfate, or magnesium lauryl sulfate, or a combination thereof. Embodiment 57: The spray-dried formulation of any one of embodiments 34 to 56, comprising about 0.5 to about 10% weight / weight of a lubricant.

[0072] Embodiment 58: The spray-dried formulation of any one of embodiments 34 to 57, comprising about 0.1 to about 5% weight / weight of a flavoring agent. Embodiment 59: The spray dried formulation of any one of embodiments 34 to 58, comprising fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a first disintegrant, a second disintegrant, a flavoring agent, and a lubricant. Embodiment 60: The spray dried formulation of any one of embodiments 34-58, comprising fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a first disintegrant, a second disintegrant, a first lubricant, a second lubricant, and a flavoring agent. Embodiment 61 The spray dried formulation of any one of embodiments 34-58, comprising fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a first disintegrant, a second disintegrant, a flavoring agent, and a lubricant.

[0073] Embodiment 62: The spray dried formulation of any one of embodiments 34-58, comprising fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, and a lubricant. Embodiment 63: The spray dried formulation of any one of embodiments 34 to 58, comprising fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, and a lubricant. Embodiment 64: The spray dried formulation of any one of embodiments 34 to 58, comprising fexofenadine zwitterion dihydrate, a first wetting agent, a second wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, and a lubricant. Embodiment 65: The spray dried product of any one of embodiments 34 to 58, comprising fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a fourth diluent, a fifth diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, and a lubricant.

[0074] Embodiment 66: The spray dried formulation of any one of embodiments 34-58, comprising fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a fourth diluent, a fifth diluent, a sixth diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, and a lubricant. Embodiment 67: The spray dried formulation of any one of embodiments 34-58, comprising fexofenadine zwitterion dihydrate, a first wetting agent, a second wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, a first lubricant, and a second lubricant. Embodiment 68: The spray dried formulation of any one of embodiments 34-58, comprising fexofenadine zwitterion dihydrate, a wetting agent, an alkalizing agent, a first buffering agent, a second buffering agent, a sweetening agent, a binder, a first diluent, a second diluent, a third diluent, a first disintegrant, a second disintegrant, a third disintegrant, a flavoring agent, a first lubricant, and a second lubricant. Embodiment 69: The spray-dried formulation of any one of embodiments 34 to 68, further comprising water.

[0075] Embodiment 70: An oral solid dosage form comprising the spray-dried formulation of any one of embodiments 34-69. Embodiment 71: The oral solid dosage form of embodiment 70, which is a solid dosage form such as a tablet, e.g., an orally disintegrating tablet, a chewable tablet, or a dispersible granule, or a liquid dosage form such as a suspension. Embodiment 72: The oral solid dosage form of embodiment 70 or 71, which is a chewable tablet. Embodiment 73: The oral solid dosage form of any one of embodiments 70-72, comprising about 10 to about 200 mg, such as about 30 to about 180 mg, or such as about 30 mg, about 60 mg, about 120 mg, or about 180 mg of fexofenadine zwitterion.

[0076] Embodiment 74: An oral solid dosage form of any one of embodiments 70 to 73, lacking a coating layer for taste masking, such as a eutagliatite polymer. Embodiment 75: A method for alleviating an allergy symptom in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the spray dried formulation of any one of embodiments 1 to 69 or the oral solid dosage form of any one of embodiments 70 to 74. Embodiment 76: The method of embodiment 75, wherein the patient is an adult. Embodiment 77: The method of embodiment 75, wherein the patient is a child.

[0077] Aspect 78: The method of any one of aspects 75 to 77, wherein the allergy is due to an indoor allergen or an outdoor allergen. Aspect 79: The method of aspect 78, wherein the indoor allergen is an indoor allergen, such as a dust mite, a pet allergen such as found in animal saliva, animal urine, or animal dander, or a mold. Embodiment 80: The method of embodiment 78, wherein the outdoor allergen is pollen, such as from grasses, weeds, or trees, e.g., hay fever, or mold. Aspect 81: The method of any one of aspects 75-80, wherein said symptom is one or more of: bloodshot eyes, itchy eyes, watery eyes, itchy nose, runny nose, stuffy nose, sneezing, stuffy nose, wheezing, coughing, chest tightness, facial pain, rash, hives, shortness of breath, coughing, post nasal drip, itchy throat, dry skin, sinus pressure, decreased sense of smell, decreased sense of taste, or decreased sleep quality.

[0078] Embodiment 82: A method for alleviating symptoms due to upper respiratory tract allergy in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the spray dried formulation of any one of embodiments 16-69 or the oral solid dosage form of any one of embodiments 70-74. Aspect 83: The method of aspect 82, wherein said symptom is runny nose, itchy, watery eyes, sneezing, itchy nose, itchy throat, or a combination thereof. Embodiment 84: The method of embodiment 82 or 83, wherein said upper respiratory tract allergy is hay fever. EXAMPLES

[0079] Example 1 - Preparation of Fexofenadine Zwitterionic Granules Granules containing fexofenadine zwitterionic granules were prepared using the ingredients in Table 1 as follows. [Table 1]

[0080] First, a fexofenadine zwitterion dihydrate suspension formulation is prepared at room temperature using a vessel equipped with a rotor-stator. Step 1: Combine Poloxamer 407 with water. Step 2: Fexofenadine hydrochloride is combined with the water + poloxamer mixture, i.e., step 1, to form a suspension. Step 3: Next, combine the suspension with an equimolar amount of fexofenadine HCl and sodium hydroxide to obtain fexofenadine zwitterion dihydrate and sodium chloride. Step 4: A phosphate buffer, such as dibasic sodium phosphate dihydrate and monobasic sodium phosphate hydrate, is added to the suspension from step 3 to maintain the pH in the range of 5.80 to about 7.0. Step 5: Add sucralose to the suspension. Step 6: Include HPMC in the suspension to obtain a final suspension pH of around 6.7.

[0081] The final suspension is then spray-dried in an inert matrix to obtain granules. Spray drying was carried out using a fluidized bed and tangential spray system. The inert matrix includes microcrystalline cellulose, mannitol, and croscarmellose sodium. After granulation, the granules were calibrated. The final formulation was prepared by blending the granules in the external phase, which was done with starch glycolate, PEG 6000, poloxamer 407, flavorings and magnesium stearate.

[0082] Examples 2 to 26 The fexofenadine zwitterion dihydrate suspensions and granules in Tables 2-26 were prepared as described in Example 1, except using the suspension and granule ingredients shown in Tables 2-26. The granules in Tables 2-26 were then combined with the external phase ingredients to provide the final fexofenadine zwitterion dihydrate formulations. [Table 2] [Table 3] [Table 4] [Table 5] [Table 6] [Table 7] [Table 8]

Table 9

Table 10

Table 11

Table 12

Table 13

Table 14

Table 15

Table 16

Table 17

Table 18

Table 19

Table 20

Table 21

Table 22

Table 23

Table 24

Table 25

[0083] Example 27: Bitterness test E-tan analysis was performed to compare the bitterness levels between samples of a suspension containing fexofenadine hydrochloride coated for taste masking (Sample 1), a fexofenadine zwitterion dihydrate of the present disclosure (Sample 2), a chewable tablet containing fexofenadine zwitterion dihydrate with grape flavor (Sample 3), a chewable formulation containing a fexofenadine zwitterion dihydrate chewable tablet with mint flavor (Sample 4), and a chewable tablet containing a spray dried fexofenadine zwitterion dihydrate of the present disclosure with grape flavor (Sample 5). The results are shown in FIG. 1. As a baseline, the bitter substance quinine was measured at various concentrations to determine the bitterness scale. Additionally, various samples were measured and the generated data was interpreted as the bitterness level of quinine hydrochloride. The results show that the bitterness level of the fexofenadine zwitterion suspension of the present disclosure is significantly lower than the composition containing fexofenadine hydrochloride.

[0084] Example 28: Characterization The fexofenadine zwitterion dihydrate prepared in Example 1 was characterized using differential scanning calorimetry (DSC) and compared to the DSC of fexofenadine hydrochloride. See, e.g., Figures 2 and 3. The results show that fexofenadine hydrochloride has a melting point of 196-200°C and fexofenadine zwitterion has a melting point of 220-230°C. DSC analysis was also performed comparing the DSC thermograms of fexofenadine zwitterion dihydrate and spray dried formulations of the present disclosure containing fexofenadine zwitterion dihydrate. These results showed that the DSC of the spray dried formulations of the present disclosure containing fexofenadine zwitterion dihydrate exhibited thermal events in the same range as the melting point of fexofenadine zwitterion.

[0085] Although the present disclosure has been described with its preferred specific embodiments, it should be understood that the foregoing description and the following examples are intended to illustrate, but not to limit, the scope of the present disclosure. It will be understood by those skilled in the art that various modifications can be made and equivalents can be substituted without departing from the scope of the present disclosure, and that other aspects, advantages, and modifications will be apparent to those skilled in the art to which the present disclosure pertains. In addition to the embodiments described herein, the present disclosure contemplates and claims inventions resulting from combinations of features of the disclosure cited herein and features of the cited prior art documents that complement the features of the present disclosure. Similarly, it will be understood that any described material, feature, or article may be used in combination with any other material, feature, or article, and such combinations are considered to be within the scope of the present disclosure. The disclosures of each patent, patent application, and publication cited or described in this specification are hereby incorporated by reference in their entirety for all purposes.

Claims

1. 1. A process for preparing a spray-dried formulation comprising fexofenadine zwitterion dihydrate, comprising: (i) spray drying a fexofenadine zwitterion dihydrate composition; and (ii) spray drying an inert matrix.

2. The process of claim 1 , wherein the inert matrix comprises one or more pharma- ceutically acceptable excipients, such as a diluent, binder, glidant, or disintegrant, or a combination thereof.

3. the diluent is microcrystalline cellulose, mannitol, maltitol, sucrose, erythritol, dibasic calcium phosphate, tribasic calcium phosphate, isomalt, xylitol, maltodextrin, lactose, starch, sorbitol, sucrose, sucrose derivatives, inverted sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, cellulose derivatives, calcium carbonate, calcium lactate, calcium sulfate, or calcium phosphate, or a combination thereof; or The disintegrant is croscarmellose sodium, sodium starch glycolate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or a combination thereof; The process according to claim 2.

4. (a) combining fexofenadine hydrochloride, water, and a wetting agent; (b) combining the product of step (a) with an alkalizing agent; (c) adjusting the pH of the product of step (b) to pH 5.8-7 with one or more buffering agents; (d) combining the product of step (c) with a sweetener; and (e) combining the product of step (d) with a binder. Further comprising: The pH of the fexofenadine zwitterion dihydrate composition is 6.5 to 7, preferably 6.

7. The process according to any one of claims 1 to 3.

5. 5. The process of claim 4, further comprising combining the spray-dried formulation with one or more of a second portion of a disintegrant, a second disintegrant, a second portion of a diluent, a flavoring agent, a second portion of a wetting agent, and one or more lubricants.

6. the second disintegrant is sodium starch glycolate, crospovidone, pregelatinized starch, starch, hydroxypropyl cellulose (HPC), or a combination thereof; or the lubricant is polyethylene glycol (PEG) such as PEG 6000, magnesium stearate, sodium stearyl fumarate, stearic acid, sorbitan monostearate, sucrose monopalmitate, glyceryl monostearate, glyceryl tribehenate, glyceryl dibehenate, calcium stearate, and zinc stearate, hydrous magnesium silicate, sodium oleate, Sterotex, sodium benzoate, talc, sodium acetate, wax, sodium lauryl sulfate, or magnesium lauryl sulfate, or a combination thereof; The process according to claim 5.

7. A product prepared according to the process of any one of claims 1 to 3.

8. A spray-dried formulation comprising fexofenadine zwitterion dihydrate and an inert matrix.

9. 9. The spray-dried formulation of claim 8, wherein the inert matrix comprises one or more pharma- ceutically acceptable excipients, such as a diluent or a first disintegrant.

10. the diluent is microcrystalline cellulose, mannitol, isomalt, xylitol, or a combination thereof, preferably microcrystalline cellulose and mannitol, preferably microcrystalline cellulose, mannitol, maltitol, maltodextrin, lactose, starch, sorbitol, sucrose, sucrose derivatives, inverted sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, cellulose derivatives, calcium carbonate, calcium lactate, calcium sulfate, or calcium phosphate, or a combination thereof; or the first disintegrant is croscarmellose sodium, sodium starch glycolate, crospovidone, pregelatinized starch, starch, hydroxypropyl cellulose (HPC), or a combination thereof; 10. The spray-dried formulation of claim 9.

11. 11. The spray dried formulation of any one of claims 8 to 10, further comprising one or more of a wetting agent, an alkalizing agent, a buffering agent, a sweetening agent, a binder, or a solvent, and optionally further comprising one or more of a second disintegrant, a flavoring agent, and a lubricant.

12. the wetting agent comprises a poloxamer, such as poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, or a combination thereof; or the alkalizing agent is a strong base such as potassium hydroxide, calcium hydroxide, sodium hydroxide, or barium hydroxide; or The buffer is dibasic sodium phosphate 2H 2 O, monobasic sodium phosphate, citric acid / dibasic sodium phosphate, dibasic sodium phosphate hydrate, succinic acid / sodium hydroxide, citric acid / sodium citrate, sodium citrate hydrate, potassium citrate, maleic acid / sodium hydroxide, fumaric acid / sodium hydroxide, monobasic sodium phosphate hydrate, monobasic potassium phosphate / dibasic sodium phosphate, dibasic sodium phosphate hydrate, dibasic potassium phosphate, dibasic potassium phosphate hydrate, or preferably monobasic sodium phosphate, monobasic sodium phosphate hydrate, monobasic sodium phosphate / dibasic sodium phosphate, dibasic sodium phosphate hydrate, dibasic potassium phosphate, or dibasic potassium phosphate hydrate, or more preferably monobasic sodium phosphate, monobasic sodium phosphate hydrate / dibasic sodium phosphate, or dibasic sodium phosphate hydrate, or combinations thereof, or preferably dibasic and monobasic; or the sweetening agent is sucralose, aspartame, acesulfame potassium, saccharin, steviol glycosides, neotame, advantame, sodium saccharin, sodium cyclamate, or ammonium glycyrrhizinate, or a combination thereof; or the binder is hydroxypropyl methylcellulose (HPMC), such as HPMC 4 mPa.s or HPMC 5 mPa.s, hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), or carboxymethyl cellulose (CMC), hydroxyethyl methyl cellulose (HEMC), or hydroxyethyl cellulose (HEC), or a combination thereof; or the second disintegrant is sodium starch glycolate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or a combination thereof; or the lubricant is polyethylene glycol, such as polyethylene glycol 6000, magnesium stearate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or a combination thereof; 12. The spray-dried formulation of claim 11.

13. The spray-dried formulation of any one of claims 8 to 10, which does not produce a bitter taste on contact with the tongue of a human subject.

14. Fexofenadine zwitterion dihydrate; Wetting agent; Alkalizing agents; Buffering agent; Sweeteners; Binder; Diluent; Disintegrant; Flavoring agents; and lubricant 20. A spray dried formulation comprising:

15. the wetting agent comprises a poloxamer, such as Poloxamer 188, Poloxamer 407, Poloxamer 237, Poloxamer 338, a polysorbate, such as Polysorbate 80 or SEPITRAP™ 80, or a polyoxyl hydrogenated castor oil, such as SEPITRAP™ 4000, or a combination thereof; or the alkalizing agent is a strong base such as potassium hydroxide, calcium hydroxide, sodium hydroxide, or barium hydroxide; or The buffer is dibasic sodium phosphate 2H 2 O, monobasic sodium phosphate, citric acid / dibasic sodium phosphate, dibasic sodium phosphate hydrate, succinic acid / sodium hydroxide, citric acid / sodium citrate, sodium citrate hydrate, potassium citrate, maleic acid / sodium hydroxide, fumaric acid / sodium hydroxide, monobasic sodium phosphate hydrate, monobasic potassium phosphate / dibasic sodium phosphate, dibasic sodium phosphate hydrate, dibasic potassium phosphate, dibasic potassium phosphate hydrate, or preferably monobasic sodium phosphate, monobasic sodium phosphate hydrate, monobasic sodium phosphate / dibasic sodium phosphate, dibasic sodium phosphate hydrate, dibasic potassium phosphate, or dibasic potassium phosphate hydrate, or more preferably monobasic sodium phosphate, monobasic sodium phosphate hydrate / dibasic sodium phosphate, or dibasic sodium phosphate hydrate, or combinations thereof, or preferably dibasic and monobasic; or the sweetening agent is sucralose, aspartame, acesulfame potassium, saccharin, steviol glycosides, neotame, advantame, sodium saccharin, sodium cyclamate, or ammonium glycyrrhizinate, or a combination thereof; or the binder is hydroxypropyl methylcellulose (HPMC), such as HPMC 4 mPa.s or HPMC 5 mPa.s, hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), or carboxymethyl cellulose (CMC), hydroxyethyl methyl cellulose (HEMC), or hydroxyethyl cellulose (HEC), or a combination thereof; or the diluent is microcrystalline cellulose, mannitol, isomalt, xylitol, maltitol, maltodextrin, lactose, starch, sorbitol, sucrose, sucrose derivatives, inverted sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, cellulose derivatives, calcium carbonate, calcium lactate, calcium sulfate, or calcium phosphate, or combinations thereof, preferably microcrystalline cellulose and mannitol; or the disintegrant is croscarmellose sodium, sodium starch glycolate, sodium starch glycolate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or a combination thereof, or a combination thereof; or the lubricant is polyethylene glycol such as polyethylene glycol 6000, magnesium stearate, sodium stearyl fumarate, stearic acid, sorbitan monostearate, sucrose monopalmitate, glyceryl monostearate, glyceryl tribehenate, glyceryl dibehenate, calcium stearate, and zinc stearate, hydrous magnesium silicate, sodium oleate, Sterotex, sodium benzoate, talc, sodium acetate, wax, sodium lauryl sulfate, or magnesium lauryl sulfate, or a combination thereof; 15. The spray-dried formulation of claim 14.

16. about 0.5 to about 10% w / w of a humectant; or from about 0.5 to about 5% w / w of an alkalizing agent; or from about 0.2 to about 10% weight / weight of a buffering agent; or from about 0.2 to about 3% weight / weight of a sweetener; or about 0.5 to about 5% weight / weight of a binder; or about 30 to about 80% weight / weight of diluent; or from about 3 to about 15% weight / weight of a disintegrant; or from about 3 to about 15% weight / weight of a disintegrant; or from about 0.5 to about 10% weight / weight of a lubricant; or From about 0.1 to about 5% w / w flavoring agent 16. The spray dried formulation of claim 14 or 15, comprising:

17. 16. An oral solid dosage form comprising the spray-dried formulation of claim 14 or 15, optionally lacking a coating layer for taste-masking, such as a eudalgrit polymer.

18. 18. The oral solid dosage form according to claim 17, which is a solid dosage form such as a tablet, e.g. an orally disintegrating tablet, chewable tablet or dispersible granule, or a liquid dosage form such as a suspension, preferably a chewable tablet, optionally comprising about 10 to about 200 mg, e.g. about 30 to about 180 mg, or e.g. about 30 mg, about 60 mg, about 120 mg, or about 180 mg of fexofenadine zwitterion.

19. 18. The spray dried formulation of claim 8, 9, 14, or 15 or the oral solid dosage form of claim 17 for relieving symptoms due to allergies, such as upper respiratory tract allergies, in a patient in need thereof.

20. 20. The spray dried formulation or oral solid dosage form of claim 19, wherein the allergy is due to an indoor allergen such as a pet allergen such as one found in dust mites, animal saliva, animal urine or animal dander, or an outdoor allergen such as mold or grass, weed or tree pollen, e.g. hay fever or mold.

Images