Fexofenadine-containing composition

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 troublesome part of many people's lives, often affecting the quality of life for adults and children. In many cases, allergies are unavoidable, 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 those containing 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 that can be unpleasant. Solid pharmaceutical preparations of fexofenadine hydrochloride available in the art are coated with a flavoring agent that masks the bitter taste. Alternatively, fexofenadine hydrochloride is mixed with a flavoring agent, but the flavoring agent cannot completely mask the unpleasant bitter taste. In addition to the bitter taste, fexofenadine hydrochloride formulations are difficult to manufacture. For example, drying fexofenadine hydrochloride formulations 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 creating unsafe working conditions. Summary of the Invention

[0004] What is needed is a more efficient, sustainable, and safe method for preparing pharmaceutical products 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 zwitterionic 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 oral solid dosage forms comprising the spray-dried formulations described herein.

[0006] In other embodiments, the present disclosure provides a method of alleviating symptoms of an allergy 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 present disclosure provides a method of alleviating symptoms of 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 is 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 particular compositions, methods, and processes disclosed. Additionally, the drawings are not necessarily drawn to scale. [Brief explanation of the drawings]

[0008] [Figure 1] Figure 1 is a bar graph comparing the bitterness of fexofenadine formulations. [Figure 2] FIG. 2 is a differential scanning calorimetry (DSC) thermogram of fexofenadine hydrochloride. [Figure 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 INVENTION

[0009] As used herein, the singular forms "a," "an," and "the" include plural referents. Reference to a particular value includes at least that particular value unless the context clearly dictates otherwise. Thus, for example, reference to "an entity" refers to at least one such entity and equivalents thereof known to those of ordinary skill in the art. When a value is expressed as an approximation by 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 will be interpreted in the particular context in which it is used. This would be understood as a matter of routine by one of ordinary skill in the art. In some cases, the number of significant figures used in a particular value may be one non-limiting method of determining the scope of the term "about." In other cases, the step numbers used in a series of values ​​can be used to determine the intended range in which the term "about" can be used for each value. Where present, all ranges are inclusive and combinable; that is, when values ​​stated in ranges are presented, they include all values ​​within that range. As used herein, data are presented with full disclosure of all significant figures; however, one skilled in the art will recognize that 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 all combinations of the list are to be construed as separate embodiments unless otherwise stated. For example, a list of embodiments presented as "A, B, or C" is to be construed 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, for brevity, described in the context of a single embodiment, may also be provided separately or in any subcombination. Furthermore, it should be noted that the claims may be drafted to exclude optional elements. Accordingly, such statements are intended as a prerequisite for using exclusive language, such as "only," "only," or the like, or for using a "negative" limitation 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 such step may also be considered a separate embodiment in itself.

[0011] The terms "patient" and "subject," as used herein, are used interchangeably to 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 upon oral administration. Such compositions are usable 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 doing so, 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 spray-dried fexofenadine zwitterion dihydrate formulations is advantageous for several reasons. For example, the process can utilize conventional techniques and, in particular, does not require specialized equipment, complex reactions, or expensive reagents. Furthermore, unlike those reported in the art, the process for preparing fexofenadine zwitterion dihydrate is efficient even for compositions containing high doses of fexofenadine zwitterion dihydrate. In particular, fexofenadine formulations in the art have been 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 humectant are combined. In some embodiments, fexofenadine hydrochloride is combined with a solution containing water and a humectant. The humectant is selected to facilitate the incorporation of fexofenadine hydrochloride into water and / or to enhance wettability. Many humectants are available, including, but not limited to, poloxamers, polysorbates, or polyoxyl hydrogenated castor oil.

[0015] The term "poloxamer," as used herein, refers to a nonionic 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 a combination thereof. The term "polysorbate," as used herein, refers to an oily liquid derived from ethoxylated sorbitan esterified with a fatty acid. 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 wetting step, the composition is combined with an alkalizing agent. The inventors have found that using an alkalizing agent reduces the amount of solids present in the composition, thereby reducing viscosity. This allows for the maintenance of the highest concentration of fexofenadine hydrochloride while spray-drying the composition in a later step. Generally, the alkalizing agent is a strong base. The inventors have found that using a strong base converts fexofenadine hydrochloride to fexofenadine zwitterion dihydrate in this step with the use of fewer solids than other routes, such as the use of a buffer. In some embodiments, the alkalizing agent is potassium hydroxide, calcium hydroxide, sodium hydroxide, or barium hydroxide, among others. In other embodiments, the alkalizing agent is potassium hydroxide. In a further embodiment, the alkalizing agent is calcium hydroxide. In yet another embodiment, the alkalizing agent is sodium hydroxide. In yet a further embodiment, 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 using 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 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 a combination 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 perceived by the human taste buds that corresponds to the taste of table salt, i.e., NaCl. The salty taste is different from the bitter taste imparted by fexofenadine hydrochloride. Furthermore, 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, saccharin sodium, sodium cyclamate, or ammonium glycyrrhizinate, or a combination 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 glycoside. 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 still further embodiments, three sweeteners are used.

[0019] A binder can be combined with the resulting sweetener-containing suspension. The binder is selected to stabilize the formulation, e.g., sterically stabilize, and to prevent particle aggregation. Examples of binders include, but are not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), 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, and in further embodiments, the composition contains three binders.

[0020] Fexofenadine zwitterionic dihydrate compositions containing an alkalizing agent, a buffering agent, a sweetening agent, and a binder have a pH of about 5.8 to about 7. In some embodiments, the pH of the fexofenadine zwitterionic dihydrate composition is 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 of the fexofenadine zwitterionic dihydrate composition is about 5.8. In a further embodiment, the pH of the fexofenadine zwitterionic dihydrate composition is about 5.9. In yet another embodiment, the pH of the fexofenadine zwitterionic dihydrate composition is about 6. In yet a further embodiment, the pH of the fexofenadine zwitterionic dihydrate composition is about 6.1. In other embodiments, the pH of the fexofenadine zwitterionic dihydrate composition is about 6.2. In further embodiments, the pH of the fexofenadine zwitterionic dihydrate composition is about 6.3. In still other embodiments, the pH of the fexofenadine zwitterionic dihydrate composition is about 6.4. In still further embodiments, the pH of the fexofenadine zwitterionic dihydrate composition is about 6.5. In still further embodiments, the pH of the fexofenadine zwitterionic dihydrate composition is about 6.6. In other embodiments, the pH of the fexofenadine zwitterionic dihydrate composition is about 6.7.In further embodiments, the pH of the fexofenadine zwitterionic dihydrate composition is from about 5.8 to about 7, from about 5.8 to about 6.9, from about 5.8 to about 6.8, from about 5.8 to about 6.7, from about 5.8 to about 6.6, from about 5.8 to about 6.5, from about 5.8 to about 6.4, from about 5.8 to about 6.3, from about 5.8 to about 6.2, from about 5.8 to about 6.1, from about 5.8 to about 6, from about 5.8 to about 5.9, from about 5.9 to about 7, from about 5.9 to about 6.9, from about 5.9 to about 6.8, from about 5.9 to about 6.7, or from about 5.8 to about 6.9. 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 its volume.

[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., granules. One feature of the processes of the present invention is this formation of granules containing fexofenadine zwitterion dihydrate. The granules produced according to these methods do not have a bitter taste, and subsequent steps on these granules do not convert the fexofenadine zwitterion dihydrate to fexofenadine hydrochloride. The granules comprise (i) the 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 several techniques and equipment. In some embodiments, spray drying is carried out using a fluidized bed and spray system. The inventors have found that a fluidized bed combines the granulation and drying steps. The spray system provides well-granulated granules. 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 pharmaceutically acceptable excipients. Desirably, the one or more pharmaceutically 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 pharmaceutically acceptable excipients maintain a pH of about 5.5 to about 7 to avoid the formation of fexofenadine hydrochloride. In other embodiments, the pharmaceutically acceptable excipients maintain a pH of 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 pharmaceutically 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 various products in the art. In still other embodiments, the diluent is mannitol having a pH of about 6 to about 7, e.g., 6.3. In a further embodiment, the diluent is maltitol. In a further embodiment, 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, or for example, 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 yet another 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 yet another embodiment, the diluent is starch. In a further embodiment, the diluent is starch having a pH of about 4 to about 8. In a still 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 embodiment, the diluent is inverted sucrose. In yet another embodiment, the diluent is lactitol. In yet another embodiment, the diluent is lactitol having a pH of about 4.5 to about 7. In another embodiment, the diluent is erythritol. In yet another embodiment, the diluent is erythritol having a pH of about 5 to about 7. In yet another embodiment, the diluent is fructose. In yet another embodiment, the diluent is glucose. In yet another embodiment, the diluent is glucose having a pH of about 4 to about 6. In yet another embodiment, the diluent is calcium carbonate. In yet another embodiment, the diluent is calcium carbonate having a pH of about 9. In another embodiment, the diluent is cellulose. In yet another embodiment, the diluent is cellulose having a pH of about 5 to about 7.5. In yet another embodiment, the diluent is a cellulose derivative. In yet another embodiment, the diluent is calcium carbonate. In yet another embodiment, the diluent is calcium lactate. In another embodiment, the diluent is calcium sulfate. In yet another embodiment, 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 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 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 embodiments, the glidant is talc. In other embodiments, 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 granules include, but are not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), carboxymethyl cellulose (CMC), hydroxyethyl methyl cellulose (HEMC), 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 still 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. Two or more binders may be used to form 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 a second portion of the disintegrant used to prepare the granules. 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 a combination thereof. In some embodiments, the disintegrant in the external phase is croscarmellose sodium. In other embodiments, the disintegrant in the external phase is sodium starch glycolate. In a further embodiment, the disintegrant in the external phase is crospovidone. In yet another embodiment, the disintegrant in the external phase is pregelatinized starch. In yet a further embodiment, the disintegrant in the external phase is starch. In another embodiment, 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 second disintegrants include sodium starch glycolate, crospovidone, pregelatinized starch, starch, hydroxypropyl cellulose (HPC), or a combination thereof. In some aspects, the second disintegrant is sodium starch glycolate. In other aspects, the second disintegrant is crospovidone. In a further aspect, the second disintegrant is pregelatinized starch. In yet another aspect, the second disintegrant is starch. In yet a further aspect, 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 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 still further embodiments, the diluent is maltitol. In a further embodiment, 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 having a pH of about 7. In yet a further embodiment, the diluent is erythritol. In a further embodiment, the diluent is erythritol having a pH of about 5 to about 7. In another embodiment, the diluent is dicalcium phosphate. In a further embodiment, 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 embodiment, the diluent is tricalcium phosphate. In a further embodiment, the diluent is tricalcium phosphate having a pH of about 6.8. In yet another 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 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 at 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 at 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 invert sucrose. In still further aspects, the diluent is lactitol. In further aspects, the diluent is lactitol having a pH of about 4.5 to about 7. In other aspects, the diluent is erythritol. In further aspects, the diluent is erythritol having a pH of about 5 to about 7. In further aspects, the diluent is fructose. In still other aspects, the diluent is glucose. In 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 further aspects, the diluent is calcium carbonate having a pH of about 9. In other aspects, the diluent is cellulose. In further aspects, the diluent is cellulose having a pH of about 5 to about 7.5. In still other 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 a further aspect, the diluent is calcium phosphate.

[0029] In yet other embodiments, the spray-dried formulation is combined with a flavoring agent 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, 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).

[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 a further embodiment, the lubricant is sodium stearyl fumarate. In yet another embodiment, the lubricant is stearic acid. In still further embodiments, the lubricant is sorbitan monostearate. In other embodiments, the lubricant is sucrose monopalmitate. In still further embodiments, the lubricant is glyceryl monostearate. In still other embodiments, the lubricant is glyceryl tribehenate. In still further embodiments, the lubricant is glyceryl dibehenate. In still other embodiments, the lubricant is calcium stearate. In still other embodiments, the lubricant is zinc stearate. In still other embodiments, the lubricant is hydrous magnesium silicate. In still further embodiments, the lubricant is sodium oleate. In still other embodiments, the lubricant is sterotex. In still other embodiments, the lubricant is sodium benzoate. In still other embodiments, the lubricant is talc. In still further embodiments, the lubricant is sodium acetate. In still other embodiments, the lubricant is a wax. In still other embodiments, the lubricant is sodium lauryl sulfate. In still other embodiments, 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 this 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 upon contact 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 a subject's taste buds or tongue. Additionally, the fexofenadine zwitterion products (formulations and compositions) defined herein can be chewed or swallowed. In some embodiments, chewing provides faster availability of fexofenadine for absorption compared to swallowed tablets, which must completely disintegrate before the fexofenadine can be absorbed. Thus, fexofenadine zwitterion can 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 vehicle for fexofenadine zwitterion dihydrate. That is, 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 fexofenadine zwitterion dihydrate. In some embodiments, the inert matrix comprises one or more pharmaceutically acceptable excipients. The one or more pharmaceutically 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, dicalcium phosphate, tricalcium 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 still further embodiments, the diluent is maltitol. In still 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 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 dicalcium phosphate. In a further embodiment, the diluent is dicalcium phosphate at a pH of about 5.1 to about 7.3, or e.g., about 7.3, or about 5.1, or about 6.1 to about 7.2. In a further embodiment, the diluent is tricalcium phosphate. In a further embodiment, the diluent is tricalcium phosphate at a pH of about 6.8. In yet another 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 yet another embodiment, the diluent is starch. In a further embodiment, the diluent is starch having a pH of about 4 to about 8. In a still 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 still further embodiments, the diluent is lactitol. In still further embodiments, the diluent is lactitol at a pH of about 4.5 to about 7. In other embodiments, the diluent is erythritol. In still further embodiments, the diluent is fructose. In still other embodiments, the diluent is glucose. In still further embodiments, the diluent is glucose at a pH of about 4 to about 6. In still further embodiments, the diluent is calcium carbonate. In still further embodiments, the diluent is calcium carbonate at a pH of about 9. In still other embodiments, the diluent is cellulose. In still further embodiments, the diluent is cellulose at a pH of about 5 to about 7.5. In still further embodiments, the diluent is a cellulose derivative. In still further embodiments, the diluent is calcium carbonate. In still further embodiments, the diluent is calcium lactate. In still other embodiments, the diluent is calcium sulfate. In still further embodiments, 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 a combination 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 still 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 humectant, alkalizing agent, buffer, sweetener, binder, or 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, 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).

[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 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. 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, dibasic sodium phosphate hydrate, dibasic potassium phosphate, and 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 phosphoric acid and monobasic phosphoric acid.

[0037] In still 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 contains one or more binders. Examples of binders include, but are not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), carboxymethylcellulose (CMC), hydroxyethyl methylcellulose (HEMC), 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 contains 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 a further aspect, the lubricant is sodium stearyl fumarate. In yet another aspect, the lubricant is stearic acid. In yet a further aspect, the lubricant is sorbitan monostearate. In another embodiment, the lubricant is sucrose monopalmitate. In a further embodiment, the lubricant is glyceryl monostearate. In yet another embodiment, the lubricant is glyceryl tribehenate. In a still further embodiment, the lubricant is glyceryl dibehenate. In another embodiment, the lubricant is calcium stearate. In a further embodiment, the lubricant is zinc stearate. In a still further embodiment, the lubricant is hydrous magnesium silicate. In a still further embodiment, the lubricant is sodium oleate. In another embodiment, the lubricant is sterotex. In a still further embodiment, the lubricant is sodium benzoate. In a still further embodiment, the lubricant is talc. In a still further embodiment, the lubricant is sodium acetate. In another embodiment, the lubricant is a wax. In a still further embodiment, the lubricant is sodium lauryl sulfate. In a still further embodiment, the lubricant is magnesium lauryl sulfate. In still further embodiments, 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 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). The spray-dried formulation may contain about 0.5 to about 10% wt / wt of one or more humectants, 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 humectants.In other embodiments, the spray-dried formulation has a saturation rate of 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 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% wt / w of one or more humectants.

[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 can contain from about 0.5 to about 5% wt / wt 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% wt / wt of one or more alkalizing agents. In other embodiments, the spray-dried formulation may comprise about 0.5 to about 5, about 0.5 to about 4.5, about 0.5 to about 4, about 0.5 to about 3.5, 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 5, about 1 to about 4.5, about 1 to about 4, about 1 to about 3.5, 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 5, about 1.5 to about 4.5, about 1.5 to about 4, about 1.5 to about 3.5, about 1.5 to about 3, 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, 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, dibasic sodium phosphate hydrate, or dibasic potassium phosphate hydrate. In further embodiments, the buffering agent is dibasic phosphate and monobasic phosphate. In some aspects, the buffering agent is sodium phosphate hydrate, e.g., 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 buffering agents. 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 buffering agents.In other embodiments, the spray-dried formulation may comprise 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, from about 2 to about 1 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% mass / mass of one or more buffers.

[0044] Examples of sweeteners include sucralose, aspartame, acesulfame potassium, saccharin, steviol glycosides, neotame, advantame, saccharin sodium, sodium cyclamate, or ammonium glycyrrhizinate, or combinations thereof. In some embodiments, the sweetener is sucralose. In other embodiments, the sweetener is aspartame. In a further embodiment, the sweetener is acesulfame potassium. In yet other embodiments, the sweetener is saccharin. In still further embodiments, the sweetener is steviol glycosides. In other embodiments, the sweetener is neotame. In a further embodiment, the sweetener is advantame. In still other embodiments, the sweetener is saccharin sodium. In still further embodiments, the sweetener is sodium cyclamate. The spray-dried formulation contains from about 0.2 to about 3% w / w 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), carboxymethylcellulose (CMC), hydroxyethyl methylcellulose (HEMC), 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. 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% wt / wt 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% wt / wt 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 a further aspect, the spray-dried formulation contains three diluents. In yet other aspects, the spray-dried formulation contains four diluents. In a still further aspect, 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, dicalcium phosphate, tricalcium 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 a combination thereof. In certain 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 further embodiments, the diluent is sucrose having a pH of about 7. In still further embodiments, the diluent is erythritol. In further embodiments, the diluent is erythritol having a pH of about 5 to about 7. In other embodiments, the diluent is dicalcium phosphate. In further embodiments, the diluent is dicalcium phosphate having 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 tribasic calcium phosphate at 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 a still 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 embodiments, the diluent is calcium carbonate. In further embodiments, the diluent is calcium carbonate with a pH of about 9. In other embodiments, the diluent is cellulose. In further embodiments, the diluent is cellulose with a pH of about 5 to about 7.5. In further embodiments, the diluent is a cellulose derivative. In still other embodiments, the diluent is calcium carbonate. In still further embodiments, the diluent is calcium lactate. In other embodiments, the diluent is calcium sulfate. In further embodiments, the diluent is calcium phosphate. The spray-dried formulation can contain about 30 to about 80% w / w of one or more diluents. In some embodiments, the spray-dried formulation contains about 30, about 40, about 50, about 60, about 70, or about 80% w / w of one or more diluents. In other embodiments, 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% wt / 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% w / w 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 to about 4 to 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 and about 14 to about 15%, about 10 to about 14, about 10 to about 13, about 10 to about 12, about 10 to about 11, about 11 to about 15, about 11 to about 14, about 11 to about 13, about 11 to about 12, about 12 to about 15, about 12 to about 14, about 12 to about 13, about 13 to about 15, about 13 to about 14, 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, 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 a further aspect, the lubricant is sodium stearyl fumarate. In yet other aspects, the lubricant is stearic acid. In still further embodiments, the lubricant is sorbitan monostearate. In other embodiments, the lubricant is sucrose monopalmitate. In still further embodiments, the lubricant is glyceryl monostearate. In still other embodiments, the lubricant is glyceryl tribehenate. In still further embodiments, the lubricant is glyceryl dibehenate. In still other embodiments, the lubricant is calcium stearate. In still other embodiments, the lubricant is zinc stearate. In still other embodiments, the lubricant is hydrous magnesium silicate. In still further embodiments, the lubricant is sodium oleate. In still other embodiments, the lubricant is sterotex. In still other embodiments, the lubricant is sodium benzoate. In still other embodiments, the lubricant is talc. In still further embodiments, the lubricant is sodium acetate. In still other embodiments, the lubricant is a wax. In still other embodiments, the lubricant is sodium lauryl sulfate. In still other embodiments, 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% w / w 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 6 to about 9, about 6 to about 7, about 6 to about 9, about 7 to about 8, about 8 to about 10, 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% 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 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 first disintegrant, a second disintegrant, a flavoring agent, and a lubricant. 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 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 oral solid dosage forms comprising the spray-dried formulation / granules or final fexofenadine zwitterionic composition 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 taste masking. In some embodiments, the oral dosage form lacks a coating layer containing a eudagrit 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, a 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 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] Oral solid dosage forms can contain fexofenadine zwitterion dihydrate in an amount 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 may comprise about 10 to about 180, about 10 to about 160, about 10 to about 140, about 10 to about 120, about 10 to about 100, about 10 to about 80, about 10 to about 60, about 10 to about 40, about 20 to about 200, about 20 to about 180, about 20 to about 160, about 20 to about 140, about 20 to about 120, about 20 to about 100, about 20 to about 80, about 20 to about 60, about 20 to about 40, about 30 to about 200, about 30 to about 180, about 30 to about 160, about 30 to about 140, about 30 to about 120, about 30 to about 30 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 In a further embodiment, the spray-dried formulation contains 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. These methods include administering a therapeutically effective amount of the spray-dried formulation or oral solid dosage form to the patient. Those skilled in the art will be able to determine appropriate allergies that can be treated using the described compositions and dosage forms. For example, the allergy can be due to indoor or outdoor allergens. In some embodiments, the allergy is due to one or more indoor allergens. Various 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 some areas, 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 due to outdoor mold.

[0056] Allergies can result in a patient experiencing a variety of symptoms. For example, a patient may experience one or more of the following: redness, itchy eyes, watery eyes, itchy nose, runny nose, nasal congestion, 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 redness of the 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 nasal congestion. In still further embodiments, the symptom is sneezing. In still other embodiments, the symptom is nasal congestion. 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 poor sleep quality. 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 alleviating symptoms of upper respiratory tract allergies in patients in need thereof. These methods comprise administering to a patient a therapeutically effective amount of a 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 a further embodiment, 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 a composition, method of preparation, and use, 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 (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. Embodiment 2: The process of embodiment 1, wherein the inert matrix comprises one or more pharmaceutically acceptable excipients. Aspect 3: The process of Aspect 1 or 2, wherein the pharmaceutically 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, dicalcium phosphate, tricalcium 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. Embodiment 8: The process of any one of embodiments 1 to 7, wherein the process is carried out using a fluidized bed and spraying system, such as tangential spraying, top spraying, or bottom spraying.

[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 to 7 using one or more buffering agents; (d) combining the product of step (c) with a sweetener; (e) combining the product of step (d) with a binder. Further including; The pH of the fexofenadine zwitterion dihydrate composition is 6.5 to 7, preferably 6.7. The process of any one of embodiments 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, wherein the process is carried out using a vessel comprising a rotor-stator homogenizer. Embodiment 12: The process of any one of embodiments 9-11, 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 said inert matrix comprises one or more pharmaceutically acceptable excipients. Embodiment 18: The spray-dried formulation of embodiment 17, wherein the one or more pharmaceutically acceptable excipients is 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, a sucrose derivative, invert sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, a cellulose derivative, 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 humectant 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 buffering agent is 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, or preferably 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, or more preferably monobasic sodium phosphate, monobasic sodium phosphate hydrate / dibasic sodium phosphate, or dibasic sodium phosphate hydrate, or combinations thereof, or preferably dibasic phosphoric acid and monobasic phosphoric acid.

[0065] Aspect 27: The spray-dried formulation of any one of Aspects 23 to 26, wherein the sweetening agent is sucralose, aspartame, acesulfame potassium, saccharin, steviol glycosides, neotame, advantame, saccharin sodium, 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 to 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; buffering agents; sweeteners; binder; Diluents; Disintegrants; Flavoring agents; and lubricant 10. A spray-dried formulation comprising:

[0067] Embodiment 35: The spray-dried formulation of embodiment 34, comprising two humectants. Aspect 36: The spray-dried formulation of aspect 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 to 36, comprising about 0.5 to about 10% wt / wt 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, which comprises two buffering agents. Aspect 41. The spray-dried formulation of any one of Aspects 34-40, wherein the buffering agent is 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, or preferably 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, or more preferably monobasic sodium phosphate, monobasic sodium phosphate hydrate / dibasic sodium phosphate, or dibasic sodium phosphate hydrate, or combinations thereof, or preferably dibasic phosphoric acid and monobasic phosphoric acid.

[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 buffering agent. 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, saccharin sodium, 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 methyl cellulose (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, a sucrose derivative, inverted sucrose, lactitol, erythritol, fructose, glucose, calcium carbonate, cellulose, a cellulose derivative, 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 between pH 5 and 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 for example 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 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, a 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 34-58, comprising fexofenadine zwitterion dihydrate, a humectant, 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 humectant, 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 humectant, 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 34-58, comprising fexofenadine zwitterion dihydrate, a humectant, 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 humectant, 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 humectant, 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 to 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, 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.

[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 eutagliatol polymer. Embodiment 75: A method of alleviating symptoms of an 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 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. Embodiment 79: The method of embodiment 78, wherein said 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 the symptom is one or more of: bloodshot eyes, itchy eyes, watery eyes, itchy nose, runny nose, nasal congestion, sneezing, stuffy nose, wheezing, cough, chest tightness, facial pain, rash, hives, shortness of breath, cough, postnasal 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 of 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 to 69 or the oral solid dosage form of any one of embodiments 70 to 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 allergy is hay fever. [Example]

[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 blended into the water + poloxamer mixture (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 was then spray-dried in an inert matrix to obtain granules. Spray drying was carried out using a fluidized bed and tangential atomization system. The inert matrix included 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, flavoring agents, 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 among the following samples: a suspension containing fexofenadine hydrochloride coated for taste masking (Sample 1), a chewable tablet containing fexofenadine zwitterion dihydrate of the present disclosure (Sample 2), a chewable tablet containing fexofenadine zwitterion dihydrate with a grape flavor (Sample 3), a chewable formulation containing a chewable tablet containing fexofenadine zwitterion dihydrate with a mint flavor (Sample 4), and a chewable tablet containing a spray-dried fexofenadine zwitterion dihydrate of the present disclosure with a grape flavor (Sample 5). The results are shown in Figure 1. As a baseline, the bitter substance quinine was measured at various concentrations to determine a bitterness scale. Additionally, the various samples were measured, and the resulting data was interpreted as the bitterness level of quinine hydrochloride. The results demonstrate that the bitterness level of the fexofenadine zwitterion suspension of the present disclosure is significantly lower than that of a 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. These 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 the fexofenadine zwitterion.

[0085] While the present disclosure has been described in conjunction with its preferred specific embodiments, it should be understood that the foregoing description and the examples that follow are intended to illustrate, but not limit, the scope of the present disclosure. Those skilled in the art will understand that various changes can be made, equivalents can be substituted, and 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 cited prior art documents that are complementary to 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 that such combinations are considered within the scope of the present disclosure. The disclosures of each patent, patent application, and publication cited or described herein are hereby incorporated by reference in their entirety for all purposes. Another aspect of the present invention may be as follows. 1. 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. [2] The process described in [1] above, wherein the inert matrix comprises one or more pharmaceutically acceptable excipients, such as a diluent, a binder, a glidant, or a 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 described in [2] above. [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 to 7 using 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 including; The pH of the fexofenadine zwitterion dihydrate composition is 6.5 to 7, preferably 6.7. The process described in any one of [1] to [3] above. [5] The process described in [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 PEG6000, 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 described in [5] above. [7] A product prepared according to any one of the steps described in [1] to [6] above. [8] A spray-dried formulation comprising fexofenadine zwitterion dihydrate and an inert matrix. [9] The spray-dried formulation described in [8], wherein the inert matrix comprises one or more pharmaceutically 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; The spray-dried preparation described in [9] above.

[11] The spray-dried formulation according to any one of [8] to

[11] above, further comprising one or more of a wetting agent, an alkalizing agent, a buffer, a sweetener, 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 potassium 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 sodium phosphate; 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; The spray-dried preparation according to

[11] above.

[13] The spray-dried preparation according to any one of [8] to

[12] above, which does not produce a bitter taste when brought into contact with the tongue of a human subject.

[14] Fexofenadine zwitterion dihydrate; Wetting agent; Alkalizing agents; buffering agents; sweeteners; binder; Diluents; Disintegrants; Flavoring agents; and lubricant 10. A spray-dried formulation comprising:

[15] The wetting agent comprises a poloxamer such as poloxamer 188, poloxamer 407, poloxamer 237, or 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 potassium 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 sodium phosphate; 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 a combination 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 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; The spray-dried preparation described in

[14] above.

[16] about 0.5 to about 10% wt / wt of a wetting agent; or about 0.5 to about 5% wt / wt of an alkalizing agent; or about 0.2 to about 10% w / w of a buffering agent; or about 0.2 to about 3% w / w of a sweetener; or about 0.5 to about 5% wt / wt of a binder; or about 30 to about 80% w / w of a diluent; or about 3 to about 15% w / w of a disintegrant; or about 3 to about 15% w / w of a disintegrant; or about 0.5 to about 10% w / w of a lubricant; or About 0.1 to about 5% w / w flavoring agent The spray-dried formulation according to

[14] or

[15] , comprising:

[17] An oral solid dosage form comprising the spray-dried formulation according to any one of

[14] to

[16] above, optionally lacking a coating layer for masking bitterness, such as a eutagliatol polymer.

[18] The oral solid dosage form according to

[17] , 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, preferably a chewable tablet, optionally containing about 10 to about 200 mg, e.g., about 30 to about 180 mg, or for example, about 30 mg, about 60 mg, about 120 mg, or about 180 mg of fexofenadine zwitterion.

[19] The spray-dried preparation according to any one of [8] to

[16] or the oral solid dosage form according to

[17] or

[18] , for alleviating symptoms caused by allergies such as upper respiratory tract allergies in a patient in need thereof.

[20] The spray-dried formulation or oral solid dosage form according to

[19] , wherein the allergy is caused by an indoor allergen such as a pet allergen 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.

Claims

1. 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.

2. The method of claim 1 , wherein the inert matrix comprises one or more pharmaceutically acceptable excipients.

3. The method of claim 2, wherein the pharmaceutically acceptable excipient is a diluent, binder, glidant, or disintegrant, or a combination thereof.

4. 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 method of claim 3.

5. (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 using 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; The method according to any one of claims 1 to 4.

6. 6. The method of claim 5, 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.

7. 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), 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 a combination thereof; The method of claim 6.

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 pharmaceutically acceptable excipients.

10. The spray-dried formulation of claim 9, wherein the pharmaceutically acceptable excipient is a diluent or a first disintegrant.

11. 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; or the first disintegrant is croscarmellose sodium, sodium starch glycolate, crospovidone, pregelatinized starch, starch, hydroxypropyl cellulose (HPC), or a combination thereof; 11. The spray-dried formulation of claim 10.

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

13. the wetting agent comprises a poloxamer; or the alkalizing agent is a strong base; 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 combinations thereof; 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), 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, magnesium stearate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or a combination thereof; 13. The spray-dried formulation of claim 12.

14. The wetting agent comprises poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, or a combination thereof; or the binder is HPMC 4 mPa.s or HPMC 5 mPa.s; or 14. The spray-dried formulation of claim 13, wherein the lubricant is polyethylene glycol 6000.

15. 15. The spray-dried formulation of any one of claims 8 to 14, which does not produce a bitter taste on contact with the tongue of a human subject.

16. Fexofenadine zwitterion dihydrate; Wetting agents; Alkalizing agents; buffering agents; sweeteners; binder; Diluent; Disintegrants; Flavoring agents; and lubricant 10. A spray-dried formulation comprising:

17. the humectant comprises a poloxamer, a polysorbate, or a polyoxyl hydrogenated castor oil, or a combination thereof; or the alkalizing agent is a strong base; 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 combinations thereof; 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), 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 a combination thereof; or the disintegrant is croscarmellose sodium, sodium starch glycolate, crospovidone, pregelatinized starch, starch, or hydroxypropyl cellulose (HPC), or a combination thereof; or the lubricant is polyethylene glycol, 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 a combination thereof; 17. The spray-dried formulation of claim 16.

18. The wetting agent comprising poloxamer 188, poloxamer 407, poloxamer 237, poloxamer 338, polysorbate 80, SEPITRAP™ 80, SEPITRAP™ 4000, or a combination thereof; or the alkalizing agent is potassium hydroxide, calcium hydroxide, sodium hydroxide, or barium hydroxide; or the binder is HPMC 4 mPa.s or HPMC 5 mPa.s; or 18. The spray-dried formulation of claim 17, wherein the lubricant is polyethylene glycol 6000.

19. 0.5 to 10% wt / wt of a humectant; or 0.5 to 5% wt / wt of an alkalizing agent; or 0.2 to 10% weight / weight of a buffering agent; or 0.2-3% w / w sweetener; or 0.5 to 5% wt / wt binder; or 30-80% w / w of diluent; or 3-15% w / w of a disintegrant; or 0.5 to 10% w / w of a lubricant; or 0.1 to 5% w / w flavoring agent 19. The spray-dried formulation of any one of claims 16 to 18, comprising:

20. An oral solid formulation comprising the spray-dried formulation of any one of claims 16 to 18.

21. An oral solid formulation as described in claim 20, lacking a coating layer for masking bitterness.

22. The oral solid formulation of claim 20, which is a solid formulation comprising 10 to 200 mg of fexofenadine zwitterion.

23. 21. The spray-dried formulation of claim 8, 9, 10, 16, 17, or 18 or the oral solid formulation of claim 20 for the relief of symptoms due to allergies in a patient in need thereof.

24. 24. The spray-dried formulation or oral solid formulation of claim 23, wherein the allergy is due to an indoor allergen or an outdoor allergen.

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