WO2005062722A2 - Fexofenadine containing pharmaceutical formulation - Google Patents

Abstract

The present invention provides an immediate release oral pharmaceutical composition comprising a therapeutically effective amount of fexofenadine or its pharmaceutically acceptable salts, a dissolution enhancing amount of a thermomelting binding agent and pharmaceutically acceptable excipients.

Description

ORAL PHARMACEUTICAL COMPOSITION

FIELD OF THE INVENTION

The present invention relates to an immediate release oral pharmaceutical composition of an antihistamine. Particularly, the present invention relates to an oral pharmaceutical composition of a piperidinoalkanol compound.

BACKGROUND OF THE INVENTION

Fexofenadine hydrochloride is a piperidinoalkanol compound with the chemical name (±)-4- [1 -hydroxy-4-[4-(hydroxydiphenylmethyl)- 1 -piperidinyl]butyl]-cγ,α-dimethylbenzeneacetic acid hydrochloride. Fexofenadine is a histamine H receptor antagonist useful as an antihistamine, anti-allergy agent and bronchodilator. It is indicated for the relief of symptoms associated with seasonal allergic rhinitis in adults and children 6 years of age and older. It is also indicated for treatment of uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 years of age and older. The recommended dose of fexofenadine for treatment of allergic rhinitis in adults is 60 mg twice daily or 180 mg once daily. The recommended dose of fexofenadine for treatment of chronic idiopathic urticaria in adults is 60 mg twice daily.

Fexofenadine hydrochloride is commercially available in the United States of America as Allegra^® capsules and Allegra tablets.

United States Patent Number 4,929,605 (priority date Oct 7, 1987, assigned to Merrell Dow) claims a composition comprising piperidinoalkanol compound, 0.1 -6% w/w of a non-ionic or cationic surfactant, and 2-50% w/w of a pharmaceutically acceptable carbonate salt. These immediate release compositions have been reported to have acceptable in-vitro dissolution characteristics and efficient bioavailability. The surfactant used may be expected to improve the wetting of the hydrophobic piperidinoalkanols, and the carbonate salt used may be expected to provide efficient disintegration of the dosage form in the gastrointestinal milieu, thereby ensuring that a greater surface area of the piperidinoalkanol compound is made available for absorption.

United States Patent Numbers 5,738,872, 5,855,912, 5,932,247 and 6,1 13,942 (priority date

Feb 28, 1995, assigned to Hncchst Marion Roussel. Inc^") relate to a pharmaceutical composition of a piperidinoalkanol compound like fexofenadine prepared by a wet granulation process comprising a diluent, a disintegrant and a solution of a binding agent. The patents focus on improving the bioavailablility of the piperidinoalkanol compounds by using wet granulation.

United States Patent Application Number 20030203020A1 (priority date Feb 28, 1995, assigned to Hoechst Marion Roussel, Inc) relates to a composition of piperidinoalkanol compounds obtained using specific excipients, and using piperidinoalkanol compound having a specific surface area greater than lm²/g. The compositions described and exemplified in this application use the method of wet granulation. The large surface area and the process of wet granulation may be expected to improve bioavailability of the piperidinoalkanol compounds. However, use of solvents may cause change in the polymorphic form of the piperidinoalkanol and may adversely affect its bioavailability.

United States Patent Number 5,290,569 (priority date Apr 12, 1990, assigned to Shionogi and Co.) relates to orally administrable coated granules. The patent claims a composition comprising granules obtained by mixing polyethylene glycol and a drug, followed by coating of the granules with a mixture of polyethylene glycol and a hydrophobic thermomelting material, the coated granules being obtained by the process of melt granulation, without the use of solvents. The granules are coated to a thickness such that the site and/or time for disintegration or dissolution can be properly regulated. The compositions therefore provide modified release of the drug contained therein. The patent does not suggest or teach immediate release oral compositions that can be obtained by the process of melt granulation.

United States Patent Number 5,476,667 (priority date Oct 16, 1990, assigned to Kabi Pharmacia) claims a method for obtaining pellets by the process of melt granulation, the process being designed to obtain pellets comprising a high dose of the drug. However, the patent does not disclose or exemplify granules of piperidinoalkanol compounds that may be obtained by melt granulation.

United States Patent Application Number 20020160050A1 (priority date Sep 28, 1999, assigned to Lundbeck) claims melt granulated substantially homogenous composition comprising one or more hydrophilic cellulose ether polymers, a hydrophilic melt binder and a drug. The compositions provide modified release of the drug contained therein, since the cellulose ether used acts as binder or matrix system that regulates release of the drug.

United States Patent Application Number 20030228368A1 (priority date Sep 28, 2001 , assigned to Johnson and Johnson) claims an edible solid composition comprising 25-40% w/w of at least one non-aqueous carrier which has a melting temperature less than about 45 degrees C, and about 15-60% w/w of at least one thermoplastic material which has a melting temperature greater than 50 degrees C. The compositions are obtained by placing a mixture of the non-aqueous carrier material, the thermoplastic material and a drug in a mold, heating the mold to 50-100 degrees C, and cooling it to 0-25 degrees C.

United States Patent Number 6,723,348 (priority date Nov 16, 2001, assigned to Ethypharm) relates to orodispersible tablets of fexofenadine, which are able to disintegrate in the buccal cavity upon contact with saliva by formation of an easy-to-swallow suspension, in less than 60 seconds containing; fexofenadine, or one of its pharmaceutically acceptable salt, in the form of coated granules, and a mixture of excipients comprising at least one disintegrating agent, a soluble diluent agent and a lubricant. The formulation of this invention is prepared by direct compression of the coated granules of fexofenadine and the mentioned excipients. The patent does not relate to conventional tablet compositions that are meant to be swallowed and which disintegrate in the gastrointestinal tract.

Piperidinoalkanol compounds like fexofenadine are hydrophobic in nature and have low water solubility. Direct compression is a method of choice for the manufacture of tablets because it involves minimum number of steps. However, we have observed that use of direct compression for preparation of compositions of fexofenadine cause problems such as capping and sticking. We have also observed that tablets made using dry granulation process do not release fexofenadine at a desirable rate. The use of wet granulation processes may cause a change in the polymorphic form of the piperidinoalkanol, and may adversely affect its bioavailability. We have surprisingly found that the problems of the prior art can be avoided by the use of melt granulation process, so that the hydrophobic piperidinoalkanol compounds are in intimate contact with the. thermomelting binding agent used. The use of the process of melt granulation as per the present invention avoids micronisation of the piperidinoalkanol compounds to increase their surface area, avoids use of surfactants and other means such as large amounts of disintegrating agents, avoids use of solvents that may have a deleterious effect on the stability of the piperidinoalkanol compounds, and at the same time provides a process that is feasible and industrially applicable.

OBJECTS OF THE INVENTION

It is an object of the present invention to provide an immediate release oral pharmaceutical composition of a piperidinoalkanol compound by melt granulation process.

It is yet another object of the present invention to provide an immediate release oral pharmaceutical composition of fexofenadine or its pharmaceutically acceptable salts' by melt granulation, such that the composition provides therapeutically effective levels of fexofenadine.

SUMMARY OF THE INVENTION The present invention provides an immediate release oral pharmaceutical composition comprising a therapeutically effective amount of fexofenadine or its pharmaceutically acceptable salts, a dissolution enhancing amount of a thermomelting binding agent and phamiaceutically acceptable excipients.

DETAILED DESCRIPTION OF THE INVENTION

Melt granulation is a known process and involves mechanically working a paniculate substance mixed with a thermomelting binder which has a melting point of 40-100°C, so as to foπn granules. During the process of manufacture, the thermomelting binding agent melts and adheres to the surface of the particulate drug. The process thus causes adhering of the particles to form granules, which are then processed by methods conventional in the art to obtain pharmaceutical compositions.

The theπnomelting binding agent is present in the oral composition of the present invention in a dissolution enhancing amount. The term "dissolution enhancing amount" as used herein means that the rate of dissolution of fexofenadine or its pharmaceutically acceptable salt in the presence of the thermomelting binding agent is greater than the rate of dissolution in the absence of the thermomelting binding agent. The amount of the thermomelting binding agent used depends on the agent used and the properties of the agent used. The thermomelting binding agent may be any suitable substance with a melting point less than about 150°C. The thermomelting binding agents used in the composition of this invention typically include hydrophobic agents, hydrophilic agents or mixtures thereof. The term "hydrophobic agent" as used herein means a substance that has a hydrophilic-lipophilic balance of less than 10, and the term "hydrophilic agent" as used herein means a substance that has a hydrophilic- lipophilic balance of greater than 10. It excludes such hydrophobic agents that in any amounts will not function to enhance dissolution of fexofenadine or its phamiaceutically acceptable salt. However, the use of the term "hydrophobic agent" is not restricted to surfactants, i.e. amphiphilic compounds that have both hydrophobic and hydrophilic properties, but hydrophobic agents such as hydrogenated vegetable oils are also useful as the thermomelting binding agent of the present invention which is capable of enhancing dissolution of fexofenadine or its phamiaceutically acceptable salt. Hydrophobic agents that are not capable by themselves of enhancing the dissolution of fexofenadine or its phamiaceutically acceptable salt, may be used in admixture with a suitable agent such that the mixture acts as a thermomelting binding agent capable of enhancing dissolution. Generally, the thermomelting binding agent may be used in an amount ranging from about 5% to about 95% by weight of the composition. In preferred embodiments, the thermomelting binding agent is used in an amount ranging from about 15% to about 75% by weight of the composition, more preferably in an amount ranging from about 30% to about 60% by weight of the composition, such that the composition provides an immediate release of fexofenadine or its pharmaceutically acceptable salt.

Examples of thermomelting binding agents that may be used in the oral pharmaceutical composition of the present invention include, but are not limited to, hydrophilic agents like polyethylene glycols having an average molecular weight of not less than about 400, preferably of not less than about 1,000, more preferably from about 2,000 to 20,000, polyethylene glycol derivatives, saccharides like D-glucose, maltose, fructose and the like, sugar alcohols like xylitol, D-mannitol, D-sorbitol and the like, surfactants like sorbitan, Pluronic F68 and the like and hydrophobic agents like straight-chain saturated hydrocarbons, fats and oils like cocoa butter, beef tallow, lard, hydrogenated soybean oil, and the like, animal and plant waxes like yellow beeswax, white beeswax and the like, higher fatty acids like stearic acid and the like, higher alcohols like stearyl alcohol and the like, hydrogenated plant oils like hydrogenated castor oil, hydrogenated rapeseed oil, hydrogenated cottonseed oil (Lubritab), polishing wax (a mixture of camauba wax and paraffin), Presirol (a mixture of glycerol mono-, di- and tripalmitates), sorbitan esters, polyglycolglyceride, polyoxyethylene stearate, glycerol esters such as glyceryl monostearate (Geleol) and glyceryl distearate (Precirol); polyoxyethylene alkyl ethers such as lauroylmacrogol glyceride (Gelucire); polyoxyethylene-polyoxypropylene block copolymers such as poloxamer and the like, and mixtures thereof. It is preferred that the thermomelting binding agent has a melting point less than 100°C. In one embodiment of the present invention, xylitol is used as the theπnomelting binding agent.

The phamiaceutically acceptable excipients that may be used in the present invention typically include one or more surfactants, disintegrants, binders, wicking agents, lubricants, fillers and the like. Examples of surfactants or wetting agents that may be used in the present invention include, but are not limited to, sodium lauryl sulfate, sorbitan fatty acid esters, polyoxyethylene stearates, polyoxyethylene fatty acid esters, poloxamers, polyoxyethylene ethers, sodium docusate, polyethoxylated castor oil and the like. Examples of disintegrants that may be used in the oral phaπnaceutical composition of the present invention include, but are not limited to, starch, cellulose derivatives, gums, crosslinked polymers and the like. Binders that may be used include one or more of starch, gelatin, sugars, cellulose derivatives, polyvinylpyrrolidone and the like. Examples of wicking agents include colloidal silicon dioxide, kaolin, titanium dioxide, fumed silicon dioxide, niacinamide, sodium lauryl sulfate, m-pyrol, vinylpyπolidone polymers such as povidone, or crosslinked polyvinylpyrrolidone such as crospovidone; cellulose and cellulose derivatives such as microcrystalline cellulose, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropyl cellulose, carboxyalkyl celluloses or crosslinked carboxyalkylcelluloses and their alkali salts; sodium starch glycolate, starch and starch derivatives, ion-exchange resins and the like and mixtures thereof. Fillers that may be used in the present invention include, but are not limited to, lactose, mannitol, calcium carbonate, dicalcium phosphate, starch, microcrystalline cellulose, and the like and mixtures thereof. Examples of lubricants include talc, magnesium stearate, calcium stearate, aluminium stearate, stearic acid, hydrogenated vegetable oils, colloidal silicon dioxide, polyethylene glycol, cellulose derivatives such as carboxyalkyl cellulose and its alkali salts, and mixtures thereof. The pharmaceutical excipients are used in amounts conventionally used in the pharmaceutical art and known to a person of skill in the art.

The oral pharmaceutical composition of the present invention is prepared by the process of melt granulation, wherein the piperidinoalkanol such as fexofenadine or its phamiaceutically acceptable salt is mixed with the thermomelting binding agent and other phamiaceutically acceptable excipients and heated in a jacketed vessel at a suitable temperature so as to obtain a molten mass. Alternatively, the thermomelting binding agent may be heated so as to obtain a molten mass and the piperidinoalkanol may be added to it later. This mass is then passed through a sieve to obtain granules, which are cooled and lubricated. The lubricated mass is then either compressed to obtain tablets, or is filled in empty gelatin capsules. In yet another process, the granules of the drug obtained from the molten mass may be mixed with placebo granules comprising conventional pharmaceutical excipients, and compressed to obtain tablets. Compressed tablets may optionally be coated with a film coat for providing aesthetic appeal and/or for masking the taste of the piperidinoalkanol. Coating may be carried out using conventional methods and agents known to a person of skill in the phaπnaceutical art.

The oral phaniiaceutical composition of the present invention has essentially the same bioavailability as that provided by commercially available compositions of fexofenadine whose New Drug Application (NDA) received approval of the United States Food and Drug Administration (USFDA). The phrase "essentially the same bioavailability" as used herein means that if a pharmaceutical composition comprising fexofenadine or its phamiaceutically acceptable salt and a pharmaceutically acceptable carrier is tested in a crossover study (usually comprising a cohort of at least 10 or more human subjects), the average Area Under the Curve (AUC) and/or the Cmax for each crossover group is at least 80% of the (corresponding) average AUC and/or Cmax observed when the same cohort of subjects is dosed with the fexofenadine formulation whose NDA received approval of USFDA. Use of AUCs, Cmax and crossover studies is, of course well understood in the art. It may also be noted that the NDA product is approved for marketing on the basis of its therapeutic efficacy and safety demonstrated in human studies. The therapeutic efficacy and safety parameter may change if there is a change in bioavailability and thus once the NDA is approved, then it continues to be manufactured in a reproducible manner to provide the same bioavailability as the originally approved product. If there is a change in the manufacturing process, then the NDA holder must submit to the USFDA data demonstrating that the bioavailability of the product obtained using the new process is the same as that of the originally approved product. If there is any change in bioavailability of the product such that the therapeutic efficacy of the drug is affected, then the NDA holder will no longer be able to market the product using the approval received on the original product, and will instead need to file a NDA for the new product to obtain USFDA approval for it.

In preferred embodiments, the phaπnaceutical compositions of the present invention are bioequivalent to commercially available preparations of fexofenadine. Approval of a generic version (Abbreviated New Drug Application, AND A) of a proprietary drug (NDA) by the USFDA, as mentioned above, requires demonstration of "chemical equivalence" (similar quantities and availability of the active ingredient in proprietary and generic formulations), and "bioequivalence" (defined by absorption parameters generally falling between 80% and 125%o of those obtained with the proprietary agent under the same testing conditions). Hence, a generic drug fonnulation to be approved by the USFDA, has to be bioequivalent to the reference listed drug or the proprietary formulation. The present invention provides a phaniiaceutical composition for the treatment of histamine-mediated conditions that releases fexofenadine in a manner to provide desirable blood level profile of fexofenadine that provides efficacy in the treatment of histamine-mediated conditions. For example, when administered as a single dose in fasted state to healthy human subjects it provides area under the plasma concentration-time curve (AUC) which is comparable to that provided by the phaniiaceutical composition of fexofenadine commercially available in the United States of America in May 2003. Alternatively, it provides peak plasma levels (C_nιax) that are comparable with those provided by the pharmaceutical composition of fexofenadine commercially available in the United States of America in May 2003. Herein, the term comparable means that 90 percent confidence intervals for die ratio of the population geometric means between the phaπnaceutical composition of the present invention and the fexofenadine composition commercially available in the United States of America, namely Allegra*, based on log-transfonned data, is contained in the limits of 70-135 percent for AUC and C_max. More preferred embodiments of the present invention are bioequivalent to fexofenadine composition commercially available in the United States of America. Bioequivalence may be determined according to USFDA guidelines and criteria.

The examples that follow are provided as illustrations and do not limit the scope of the present invention. Comparative Example 1

Oral pharmaceutical composition in the fonn of tablets comprising fexofenadine hydrochloride was prepared as per Table 1 below. Table 1

Fexofenadine hydrochloride was mixed with direct compression grade lactose, Prosolv

SMCC 90, sodium lauryl sulfate, colloidal silicon dioxide and magnesium stearate and blended to obtain a mixture. The blend obtained had a poor flow, causing problems during compression. The tablets obtained had a high disintegration time. Comparative Example 2

Oral phaniiaceutical composition in the fonn of tablets comprising fexofenadine hydrochloride was prepared as per Table 2 below. Table 2

Fexofenadine hydrochloride was mixed with dibasic calcium phosphate, Prosolv SMCC 90, microcrystalline cellulose, sodium lauryl sulfate, colloidal silicon dioxide and magnesium stearate and blended to obtain a mixture. The mixture obtained was compressed to obtained tablets. The tablets thus obtained were subjected to dissolution testing using United States Phaπnacopoeia dissolution apparatus, type II, at a speed of 50 rpm. The dissolution medium used was 1800ml of 0.001M HC1. The dissolution was compared with that of Allegra^® tablets. The results are recorded in Table 3 below. Table 3

As is seen in Table 3 above, the release of fexofenadine hydrochloride from the tablets of comparative example 2 was not comparable to that from Allegra^® tablets. Example 1 The oral phaniiaceutical composition of the present invention was obtained as per the method given in Table 4 below. Table 4

Fexofenadine hydrochloride used had a particle size such that 90% of the particles are about 25 microns in diameter. Xylitol, PVP K30 and sodium lauryl sulfate were sifted through a sieve #40 ASTM (ASTM stands for American Society for Testing and Materials) and mixed together in a polybag. The above blend and Fexofenadine hydrochloride were taken in a stainless steel vessel and mixed well. The blend was heated in a stainless steel vessel using water bath maintained at 75-85°C and mixed continuously till a granular mass was obtained. The hot granulated mass was cooled to approximately 70°C with stimng and passed through ASTM 8# sieve. The granules were cooled for 7 hours. The cooled granules were then sifted through ASTM 20# sieve. The granules were blended with Avicel PH 200, sodium lauryl sulfate, colloidal silicon dioxide, sodium starch glycolate and talc. The blend was lubricated with magnesium stearate and compressed into tablets at 600 mg tablet weight. Core tablets were coated using Opadry 035B6773 (Brown).

The dissolution profile of the composition of the example 1 was compared with the Allegra^® tablets. The dissolution apparatus used was USP Type II at 50 rpm and the dissolution medium was 1800 ml of 0.001 M HC1. The results are given in table 5 below. Table 5

Examples 2 - 10

The oral phaniiaceutical compositions of the present invention were obtained as per the method given in Table 6 and Table 7 below.

Table 6

Table 7

Holt melt granulation of fexofenadine hydrochloride and the binding agent was carried out as mentioned in example l above. Placebo granules comprising lactose monohydrate, com starch and PVP K-30 were prepared by conventional wet granulation process and mixed with the melt-granulated product in amounts as specified in Table 6 above. The granules thus obtained were mixed with the extragranular excipients mentioned in Table 6 and compressed to obtain tablets.

The dissolution profile of the compositions of the examples 2-10 was compared with the Allegra ' tablets ( 180mg). The dissolution apparatus used was USP Type II at 50 rpm and the dissolution medium was 1800 ml of 0.001 M HCl. The results are given in table 8 below. Table 8

Example 11 The oral phaniiaceutical composition of the present invention was obtained as per the method given below in Table 9. Table 9

Holt melt granulation of fexofenadine hydrochloride and xylitol was carried out as mentioned in example 1. Placebo granules comprising lactose monohydrate, corn starch and PVP K-30 were prepared by conventional wet granulation process and mixed with the melt-granulated product. The granules thus obtained were mixed with the extragranular excipients and compressed to obtain tablets. The dissolution profile of the composition of the tablets thus obtained was compared with the Allegra^® tablets. The dissolution apparatus used was USP • Type II at 50 rpm and the dissolution medium was 1800 ml of 0.001 M HCl. The results are given in table 10 below. Table 10

Example 12

The oral phaniiaceutical composition of the present invention was obtained as per the method given below in Table 11. Table 11

Fexofenadine hydrochloride having a particle size such that d₉₀ is about 25 microns is used for this composition. Xylitol, PVP K30 and sodium lauryl sulfate were sifted through ASTM #40 and mixed in a polybag. Fexofenadine hydrochloride was then added to this mixture. The blend thus obtained was heated in a stainless steel vessel using a water bath maintained at 80+10°C, and mixed continuously to obtain a granular mass. The mass was cooled to room temperature for about 2 hours, followed by sifting of the granules through ASTM #20. The granules were then mixed with Avicel PH 200, starch 1500, sodium lauryl sulfate, colloidal silicon dioxide, sodium starch glycolate, talc and magnesium stearate. This mixture was then compressed to obtain tablet cores that were then coated with Opadry to a weight gain of about 3% by weight of the core.

The dissolution profile of the coated tablets thus obtained was compared with the Allegra^® tablets. The dissolution apparatus used was USP Type II at 50 rpm and the dissolution medium was 1800 ml of 0.001 M HCl. The results are given in table 12 below. Table 12

Example 13

The bioavailability of the pharmaceutical composition of fexofenadine hydrochloride (Example 12) of the present invention and that of commercially available fexofenadine hydrochloride tablets, Allegra^® (180 mg fexofenadine hydrochloride, Aventis, Inc., USA), were studied. A single-dose, open label, randomized, comparative and two-way crossover study, with a seven-day washout period, was undertaken for the same.

The pham acokinetic assessment was based on the plasma levels of fexofenadine hydrochloride measured by blood sampling. Blood samples were obtained before dosing and at the following times after administration of both the reference and test medications: 0.5, 1.0, L5, 1.75, 2.0, 2.25, 2.5, 2.75, 3.0, 3.5, 4.0, 6.0, 8.0, 12.0, 16.0 and 24.0 hours.

Eleven healthy male volunteers were enrolled for the study and all of them completed the two-way crossover study. The subjects were fasted overnight before dosing and for 4 hours thereafter. Drinking water was prohibited 2 hours before dosing and 2 hours thereafter, but was allowed ad lib at all other times. Standard meals were provided at 4, 8 and 12 hours after dosing, and at appropriate times thereafter. Meal plans were identical for both the periods.

Subjects received a single tablet of fexofenadine hydrochloride (180 mg, Example 12) with 240ml of drinking water at ambient temperature as the test medication, and a single oral dose of Allegra^® (180 mg fexofenadine hydrochloride) also with 240ml of drinking water at ambient temperature as the reference medication.

The plasma concentration of fexofenadine hydrochloride was detennined for samples collected at different time points and averaged over the eleven volunteers. The data is given in Table 13 below. Table 13

The pharmacokinetic parameters calculated using the Win Nonlin software are given in Table 14 below. Table 14

Thus, the phaniiaceutical composition of example 12 was found to be bioequivalent to Allegra^®.

Wliile the invention has been described by reference to specific embodiments, this was done for purposes of illustration only and should not be construed to li it the spirit or the scope of the invention.

Claims

1. An immediate release oral pharmaceutical composition comprising a therapeutically effective amount of fexofenadine or its pharmaceutically acceptable salts, a dissolution enhancing amount of a thermomelting binding agent and phamiaceutically acceptable excipients.

2. An immediate release oral phannaceutical composition as claimed in claim 1 , wherein the theπnomelting binding agent is selected from a hydrophilic agent, a hydrophobic agent and mixtures thereof.

3. An immediate release oral phaπnaceutical composition as claimed in claim 2, wherein the hydrophilic agent is selected from the group comprising polyethylene glycols and derivatives thereof, saccharides, sugar alcohols, hydrophilic surfactants and mixtures thereof.

4. An immediate release oral pharmaceutical composition as claimed in claim 2, wherein the hydrophobic agent is selected from the group comprising waxes, higher fatty acids, higher fatty alcohols, straight-chain saturated hydrocarbons, fats, hydrogenated vegetable oils, glycerol esters, polyoxyethylene alkyl ethers, polyoxyethylene-polyoxypropylene block copolymers, and mixtures thereof

5. An immediate release oral phannaceutical composition as claimed in claim 2, wherein the hydrophilic agent is a sugar alcohol selected from xylitol, mannitol, sorbitol and mixtures thereof.

6. An immediate release oral phannaceutical composition as claimed in claim 2, wherein the thermomelting binding agent is used in an amount ranging from about 5% to about 95% by weight of the composition.

7. An immediate release oral pharmaceutical composition as claimed in claim 5, wherein the thennomelting agent is xylitol.

8. An immediate release oral phannaceutical composition as claimed in claim 7, wherein xylitol is present in an amount ranging from about 30% to about 60% by weight of the composition.

9. An immediate release oral phannaceutical composition as claimed in claim 1 , wherein the pharmaceutically acceptable excipients is selected from one or more of surfactants, disintegrants, binders, wicking agents, lubricants and fillers.

10. An immediate release oral phannaceutical composition as claimed in claim 1 , wherein the composition has essentially the same bioavailability as commercially

aιlable fexofenadine composition whose New Drug Application received approval of United States Food and Drug Administration.