Technical Field of the Invention
The present invention relates to water-dispersible pharmaceutical compositions comprising a combination of anti-retroviral drugs useful for the treatment of HIV (Human Immunodeficiency Virus) infections; and process for preparation of said pharmaceutical compositions.
Background of the Invention
Human immunodeficiency virus (HIV) has been implicated as the primary cause of the slowly degenerate disease of the immune system termed acquired immune deficiency syndrome (AIDS). AIDS predisposes subjects to fatal opportunistic infections. Characteristically, AIDS is associated with a progressive depletion of T-cells, especially the helper-inducer subset bearing the CD4 surface marker. HIV is cytopathic and appears to preferentially infect and destroy T-cells bearing the CD4 marker.
Currently several antiretroviral drugs are available, which inhibit the growth and replication of HIV at various stages of its life cycle, such as reverse transcriptase inhibitors (RTI's), protease inhibitors and fusion inhibitors. The RTI's inhibit the reverse transcriptase enzyme. This enzyme synthesizes double-stranded DNA from the retrovirus' own single-stranded RNA genome. This DNA double helix gets integrated into the host cell's chromosomes as a provirus. Transcription then leads to copies of the viral RNA genome, from which the virus's own proteins and enzymes are formed. New viral particles then bud from the membrane of the cell. Thus, reverse transcriptase inhibition is essential for inhibiting viral replication. RTI's fall into two categories." nucleoside/nucleotide analogs such as lamivudine, stavudine, zidovudine, didanosine, abacavir, tenofovir, emtricitabine and zalcitabine; and non-nucleoside analogs such as nevirapine, delavirdine and efavirenz.
U.S. Pat. No. 5,047,407 discloses lamivudine and its use in the treatment and prophylaxis of viral infections.
Nevirapine is a known agent for the treatment of HIV infection and its synthesis and use are described in various publications including, inter alia, U.S. Pat. No. 5,366,972 and European Patent Application No. 429,987.
Stavudine or 2',3'-didehydro-3'-deoxythymidine (d4T), is a potent inhibitor of HIV reverse transcriptase in vitro reported by S.A. Riddler, et al in Antiviral Research, 1995, vol. 27, pp. 189-203.
Development of resistance has recently become a major concern in the treatment of HIV infections. Resistance usually occurs when the drugs being used are not potent enough to completely stop virus replication. Moreover, the HIV virus is able to mutate or change frequently and develop resistance to drugs, making HIV infection and AIDS very difficult to treat. Once a mutation occurs, it then grows unchecked and soon becomes dominant strain of the virus in the individual. The drug becomes progressively weaker against the new strain.
Several studies have proven that combining two drugs delays the development of resistance to one or both drugs compared to when either drug is used alone. Combination therapy might help prevent drug failure caused by viral resistance and might decrease the amount of free virus that can infect other cells. Some of the available agents appear to have benefit only in combination therapy regimens. Most combinations comprise of two anti-retroviral drugs, such as a combination of a protease inhibitor and a RTI, or a combination of nucleoside RTI and a non-nucleoside RTI. It has also been found that therapy using combinations of three or more drugs, such as a protease inhibitor or an non-nucleoside RTI with two nucleoside RTI, may greatly reduce disease progression and deaths in people with AIDS. Such a therapy is also called as HAART (Highly Active Anti-Retroviral Therapy).
However, the success of combination therapy for HIV often requires strict compliance with a complex treatment regimen that can require the administration of many different drugs per day, administered at precisely timed intervals with careful attention to diet. Such complex treatment regimens may lead to potential compliance problems related to non-adherence to therapy. Patient non-compliance may be a
serious problem in the treatment of HIV because such non-compliance may lead to the emergence of multiple-drug resistant strains of HIV. An effort to simplify treatment regimens for HIV with the goal of enhancing patient compliance by providing a simplified dosage form was made by designing Fixed-Dose Combinations (FDC's), which combine two, or more active drugs in one tablet or capsule.
PCT Application No. WO 98/18477 discloses solid dosage forms such as tablet and capsules of a combination of lamivudine and zidovudine with a pharmaceutical glidant which prevents segregation of drugs leading to a homogeneous mixture, thus increasing efficacy.
South African Application No. 2001/10499 discloses pharmaceutical compositions of a combination of lamivudine, stavudine and nevirapine, or pharmaceutically acceptable derivatives thereof, and method of preparing such compositions. It describes compositions wherein the said combination is provided as a bi-layered tablet.
South African Application No. 2001/10501 discloses pharmaceutical compositions of a combination of lamivudine and stavudine or pharmaceutically acceptable derivatives thereof, and method of preparing such compositions. It describes compositions wherein the said combination is provided as a bi-layered or a conventional tablet.
All compositions as described above are solid dosage forms either in the form of tablet or capsule, which needs to be swallowed. Many patients may have difficulty in swallowing such tablets and capsules, and consequently may not take medications as prescribed. This may particularly be true for pediatric and geriatric patients. This may result in a high incidence of non-compliance and ineffective therapy, which may prove to be fatal in case of a progressive condition like AIDS.
Thus, there is a need in the art for solid dosage forms comprising one or more anti-retroviral drugs, which can be taken orally without the need of swallowing. It is an object of the present invention to provide compositions, which readily disperse in
water or a suitable vehicle of administration and can be taken orally, thus overcoming the problems as described in the art.
Summary of the Invention
In one aspect, it relates to a water-dispersible pharmaceutical composition for oral administration comprising an anti-retroviral drug and pharmaceutically acceptable excipients selected from a group comprising diluent, disintegrant, binder, lubricant and glidant.
In another aspect, it relates to a water-dispersible pharmaceutical composition for oral administration comprising:
a) a combination of at least two anti-retroviral drugs;
b) pharmaceutically acceptable excipients selected from a group comprising diluent, disintegrant, binder, lubricant and glidant.
In another aspect, it relates to a water-dispersible pharmaceutical composition for oral administration comprising:
a) an intragranular portion comprising atleast one anti-retroviral drug and one or more of a diluent, disintegrant, binder, lubricant and glidant; and
b) an extragranular portion comprising atleast one anti-retroviral drug and one or more of a diluent, disintegrant, binder, lubricant and glidant.
In another aspect, it relates to a water-dispersible pharmaceutical composition for oral administration comprising:
a) an intragranular portion comprising one or more of a diluent, disintegrant, binder, lubricant and glidant; and
b) an extragranular portion comprising atleast one anti-retroviral drug and one or more of a diluent, disintegrant, lubricant and glidant.
In another aspect, it relates to a water-dispersible tablet for oral administration comprising:
a) an intragranular portion comprising a diluent, disintegrant and optionally a binder; and
b) an extragranular portion comprising lamivudine, stavudine and one or more of a diluent, disintegrant, lubricant and glidant.
In another aspect, it relates to a water-dispersible tablet for oral administration comprising:
a) a first granular portion comprising diluent, disintegrant and optionally a binder;
b) a second granular portion comprising stavudine and one or more of a diluent, lubricant and glidant; and
c) an extragranular portion comprising lamivudine and one or more of a diluent, disintegrant, lubricant and glidant.
In another aspect, it relates to a water-dispersible tablet for oral administration comprising:
a) an intragranular portion comprising nevirapine, diluent, disintegrant and optionally a binder; and
b) an extragranular portion comprising lamivudine, stavudine, and one or more of a diluent, disintegrant, lubricant and glidant.
In another aspect, it relates to a water-dispersible tablet for oral administration comprising:
a) a first granular portion comprising nevirapine, diluent, disintegrant and optionally a binder;
b) a second granular portion comprising diluent, disintegrant and optionally a binder; and
c) an extragranular portion comprising lamivudine, stavudine and one or more of a diluent, disintegrant, lubricant and glidant.
In another aspect, it relates to a water-dispersible tablet for oral administration comprising:
a) a first granular portion comprising nevirapine, diluent, disintegrant and optionally a binder;
b) a second granular portion comprising stavudine and one or more of a diluent, lubricant and glidant; and
c) an extragranular portion comprising lamivudine, lubricant, glidant and optionally a diluent.
In another aspect, it relates to a process for preparation of a water-dispersible pharmaceutical composition for oral administration, wherein the process comprises:
a) preparing a blend of one or more of pharmaceutically acceptable excipients selected from a group comprising diluent, disintegrant, binder, lubricant, glidant and optionally an anti-retroviral drug;
b) granulating the blend of step (a);
c) blending the granules obtained in step (b) with one or more of pharmaceutically acceptable excipients selected from a group comprising diluent, disintegrant, lubricant, glidant, and at least one anti-retroviral drug; and
d) processing the blend of step (c) into a pharmaceutical composition.
In another aspect, it relates to a process for preparation of a water-dispersible tablet for oral administration, wherein the process comprises:
a) preparing a blend of diluent, disintegrant and optionally a binder;
b) granulating the blend of step (a) with water or an aqueous solution of a binder;
c) drying the granules;
d) blending the granules with lamivudine, stavudine and one or more of a diluent, disintegrant, lubricant and glidant; and
e) compressing the blend of step (d) into a tablet.
In another aspect, it relates to a process for preparation of a water-dispersible tablet for oral administration, wherein the process comprises:
a) preparing a first granular portion by blending a diluent, disintegrant and optionally a binder, granulating the blend with water or an aqueous solution of a binder and drying the granules;
b) preparing a second granular portion by blending stavudine and one or more of a diluent, lubricant and glidant, compacting the blend and milling;
c) blending the granules obtained in step (a) and (b) with lamivudine and one or more of a diluent, disintegrant, lubricant and glidant; and
d) compressing the blend of step (c) into a tablet.
In another aspect, it relates to a process for preparation of a water-dispersible tablet for oral administration, wherein the process comprises:
a) preparing a blend of nevirapine, diluent, disintegrant and optionally a binder;
b) granulating the blend of step (a) with water or an aqueous solution of a binder;
c) drying the granules;
d) blending the granules obtained in step (c) with lamivudine, stavudine and one or more of a diluent, disintegrant, lubricant and glidant; and
e) compressing the blend of step (d) into a tablet.
In another aspect, it relates to a process for preparation of a water-dispersible tablet for oral administration, wherein the process comprises:
a) preparing a first granular portion by blending nevirapine, diluent, disintegrant and optionally a binder, granulating the blend with water or an aqueous solution of a binder and drying the granules;
b) preparing a second granular portion by blending diluent and disintegrant, granulating the blend with water and drying the granules;
c) blending the granular portions obtained in step (a) and (b) with lamivudine, stavudine, and one or more of a diluent, disintegrant, lubricant and glidant; and
d) compressing the blend of step (e) into a tablet.
In another aspect, it relates to a process for preparation of a water-dispersible tablet for oral administration, wherein the process comprises:
a) preparing a first granular portion by blending nevirapine, diluent, disintegrant and optionally a binder, granulating the blend with water or an aqueous solution of a binder and drying the granules;
b) preparing a second granular portion by blending stavudine and one or more of a diluent, lubricant and glidant, compacting the blend and milling;
c) blending the granular portions of step (a) and (b) with lamivudine and one or more of a diluent, disintegrant, lubricant and glidant; and
d) compressing the blend of step (c) into a tablet.
Detailed Description of the Invention
The term "water dispersible" as used herein is intended to describe compositions that disintegrate and readily disperse in water or a suitable vehicle of administration in less than one minute.
The term "anti-retroviral drugs" as described herein includes drugs or compounds intended for treating, reversing, reducing or inhibiting retroviral infections, in particular infections caused by HIV. The anti-retroviral drug may be selected from the various classes of drug such as nucleoside or non-nucleoside reverse transcriptase inhibitor or protease inhibitor. Nucleoside reverse transcriptase inhibitors may include lamivudine, zidovudine, stavudine, abacavir, adefovir, tenofovir, emtricitabine, zaicitabine and didanosine. Non-nucleoside reverse transcriptase inhibitors may include efavirenz, nevirapine and delavirdine. Protease inhibitors may include indinavir, nelfinavir, lopinavir, ritonavir, saquinavir, amprenavir, atazanavir, tipranavir and fosamprenavir.
The compositions according to the present invention have been exemplified by lamivudine, stavudine, nevirapine and combinations thereof.
The drug "lamivudine" as used herein includes lamivudine base as well as any pharmaceutically acceptable salt, solvate, enantiomer, ester, polymorph thereof or any compound, which upon administration to the recipient, is capable of providing lamivudine or any active metabolite or residue thereof, either directly or indirectly. Lamivudine may be present in an amount ranging from about 1 % to about 20 % by weight of the composition.
The drug "stavudine" as used herein includes stavudine base as well as any pharmaceutically acceptable salt, solvate, enantiomer, ester, polymorph thereof or any compound, which upon administration to the recipient, is capable of providing stavudine or any active metabolite or residue thereof, either directly or indirectly. Stavudine may be present in an amount ranging from about 0.5 % to about 10 % by weight of the composition.
The drug "nevirapine" as used herein includes nevirapine base as well as any pharmaceutically acceptable salt, solvate, enantiomer, ester, polymorph thereof or any compound, which upon administration to the recipient, is capable of providing nevirapine or any active metabolite or residue thereof, either directly or indirectly. Nevirapine may be present in an amount ranging from about 5 % to about 30 % by weight of the composition.
The pharmaceutical compositions as described herein are meant for oral administration and may be utilized in the form of granules or tablets. More particularly, the compositions are meant to be dispersed in water or other suitable vehicle prior to administration. The pharmaceutical compositions as described herein disperse in water in less than one minute. The dispersion formed is visually uniform with no substantial sedimentation and does not exhibit any feeling of grittiness in the mouth on oral intake.
The pharmaceutical compositions as described herein may include pharmaceutically acceptable excipients like diluents, binders, disintegrants, lubricants and glidants.
Diluents may be selected depending upon the compatibility with the active ingredient. Diluents that may be used include saccharides like lactose, dextrose, sucrose, fructose, maltose; sugars like mannitol, erythritol, sorbitol, xylitol and lactitol; cellulose derivatives like powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, dicalcium phosphate, tribasic calcium phosphate, calcium sulphate, calcium carbonate and the like. Particularly suitable diluents are lactose, microcrystalline cellulose and silicified microcrystalline cellulose. The diluent

may be used in an amount ranging form about 25 % to about 75 % by weight of the composition.
Disintegrants play a major role in the disintegration of compositions as described herein. The disintegrant may be selected from sodium starch glycolate, cross-linked carboxymethylcellulose and its sodium salt, cross-linked polyvinylpyrrolidone, pregelatinised starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, alginates and the like. Particularly suitable disintegrant is sodium starch glycolate. The amount of the disintegrant may vary from 1 % to 20 % by weight of the composition.
Binders are generally used in a solid dosage form to impart cohesive properties to a powdered blend. Binder may be a dry binder such as microcrystalline cellulose, which is particulary useful in a dry granulation process. Binder may also be selected from the group comprising gums like acacia, guar gum, alginic acid, sodium alginate; starch derivatives like corn starch, pregelatinised starch; polyvinylpyrrolidone, ethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxyvinyl polymers like carbomers, acrylates like Eudragits and other such materials routinely used in the art of solid dosage form manufacturing. Particularly suitable binder is polyvinyl pyrrolidone. The binder may be present in an amount varying from about 0.5 % to about 15 %, by weight of the composition.
Lubricant may be selected from the group consisting of talc, magnesium stearate, zinc stearate, calcium stearate, sodium stearyi fumarate and stearic acid; whereas glidants may be selected from talc, colloidal silicon dioxide, and the like. The lubricant and glidant may be used in a concentration of 0.1 % to 2 % by weight of the composition.
The compositions as described herein may also include additional excipients like sweeteners, flavors and colors. Sweeteners may be selected from the group consisting of aspartame, saccharine sodium, sucrose, dextrose, fructose, sorbitol and the like.
The compositions as described herein may be prepared by direct compression or a granulation process, such as wet or dry granulation or a combination of wet and dry granulation. In direct compression, one or more anti-retroviral drugs may be blended with pharmaceutically acceptable excipients like diluent, disintegrant, binder, lubricant and glidant and compressed into a tablet. In wet granulation, a blend comprising pharmaceutically acceptable excipients like diluent and disintegrant, and optionally an anti-retroviral drug, may be granulated with a solution or dispersion of the binder. Alternatively, the binder may be added to the above blend and the resulting blend granulated with a suitable solvent. The granules obtained may be dried, and if needed, sized and subsequently blended with one or more anti-retroviral drugs or granules of one or more anti-retroviral drugs, and pharmaceutically acceptable excipients like diluent, disintegrant, lubricant and glidants and compressed into a tablet.
Dry granulation may be carried out by slugging or roller compaction, particularly suitable is roller compaction. In one aspect of the process, one or more anti-retroviral drug and one or more of pharmaceutical excipient selected from diluent, disintegrant, binder or lubricant are blended and transferred to a roller compactor in a known manner and compacted into a sheet. The compact sheet may then be fed to a mill, such as an oscillatory mill filled with a screen. After passing through the mill and the screen, the compact gets converted into granules of desired particle size distribution. The granules may further be mixed with one or more anti-retroviral drugs or granules of one or more anti-retroviral drugs, and pharmaceutically acceptable excipients like diluent, disintegrant, lubricant and glidant and compressed into a tablet.
In one embodiment, a water-dispersible tablet for oral administration may be prepared by
preparing a blend of one or more of a diluent, disintegrant, binder, lubricant and
optionally an anti-retroviral drug selected from nevirapine, stavudine or
lamivudine;
granulating the blend by either wet or dry granulation;
blending the granules with one or more a diluent, disintegrant, binder, lubricant,
glidant and at least one anti-retroviral drug selected from nevirapine, stavudine
or lamivudine; and
compressing the blend into a tablet
In another embodiment, a water-dispersible tablet for oral administration may be prepared by
preparing a blend of diluent and disintegrant;
granulating the blend with water;
drying the granules;
blending the granules with lamivudine, stavudine, lubricant and glidant; and
compressing the blend into a tablet.
In another embodiment, a water-dispersible tablet for oral administration may be prepared by
preparing a first granular portion by blending a diluent and disintegrant,
granulating the blend with water and drying the granules;
preparing a second granular portion by blending stavudine, binder and lubricant,
compacting the blend and milling;
blending the granules obtained above with lamivudine, lubricant and glidant; and
compressing the blend into a tablet.
In another embodiment, a water-dispersible tablet for oral administration may be prepared by
preparing a blend of a nevirapine, diluent and disintegrant;
granulating the blend with an aqueous solution of a binder;
drying the granules;
blending the granules with lamivudine, stavudine, diluent, disintegrant, lubricant
and glidant; and
compressing the blend into a tablet.
In another embodiment, a water-dispersible tablet for oral administration may be
prepared by
preparing a first granular portion by blending nevirapine, diluent and disintegrant, granulating the blend with an aqueous solution of binder and drying the granules;
preparing a second granular portion by blending diluent and disintegrant and granulating the blend with water and drying the granules; blending the first and second granular portions with lamivudine, stavudine, diluent, lubricant and glidant; and compressing the blend into a tablet.
In another embodiment, a water-dispersible tablet for oral administration may be prepared by
preparing a first granular portion by blending nevirapine, diluent and
disintegrant, granulating the blend with an aqueous solution of a binder and
drying the granules;
preparing a second granular portion by blending stavudine, diluent, lubricant and
glidant, compacting the blend and milling;
blending the granules obtained above with lamivudine, diluent, lubricant and
glidant; and
compressing the blend into a tablet.
In another embodiment, a water-dispersible tablet for oral administration may be prepared by
preparing a first granular portion by blending nevirapine, diluent and
disintegrant, granulating the blend with water and drying the granules;
preparing a second granular portion by blending stavudine, diluent, lubricant and
glidant, compacting the blend and milling;
blending the granules obtained above with lamivudine, diluent, disintegrant,
lubricant and glidant; and
compressing the blend into a tablet.
The pharmaceutical compositions as described herein may further be illustrated by the following examples but these should not be construed as limiting the scope of the invention:
EXAMPLE 1

(Example Removed)
PROCEDURE: A first granular portion was prepared by granulating a blend of nevirapine and lactose with an aqueous solution of polyvinyl pyrrolidone. A second granular portion was prepared by granulating a blend of microcrystalline cellulose and sodium starch glycolate with water. The first and the second granular portions were subsequently blended with lamivudine and stavudine. The blend obtained was mixed with microcrystalline cellulose, colloidal silicon dioxide, aspartame, flavor and magnesium stearate; and was compressed into a tablet using appropriate tooling.
EXAMPLE 2

(Example Removed)

PROCEDURE: Nevirapine, lactose and sodium starch glycolate were blended and subsequently granulated with an aqueous solution of polyvinyl pyrrolidone. The granules were blended with lamivudine and stavudine. The blend obtained was mixed with silicified microcrystalline cellulose, sodium starch glycolate, co))o)da) silicon dioxide, aspartame, flavor and magnesium stearate; and was compressed into a tablet using appropriate tooling.
EXAMPLE 3

(Example Removed)
PROCEDURE: A first granular portion was prepared by granulating a blend of nevirapine, microcrystalline cellulose and sodium starch glycolate with purified water, and drying the granules. A second granular portion was prepared by blending stavudine, microcrystalline cellulose, colloidal silicon dioxide and magnesium stearate, compacting the blend in a roller compactor and milling the compacts. The first and the second granular portions were subsequently blended with lamivudine, microcrystalline cellulose, colloidal silicon dioxide, aspartame, flavor and magnesium stearate, and compressed into a tablet using appropriate tooling.
EXAMPLE 4

(Example Removed)
PROCEDURE: A first granular portion was prepared by granulating a blend of nevirapine, lactose and sodium starch glycolate with an aqueous solution of polyvinyl pyrrolidone, and drying the granules. A second granular portion was prepared by blending stavudine, microcrystalline cellulose, colloidal silicon dioxide and magnesium stearate, compacting the blend in a roller compactor and milling the compacts. The first and the second granular portions were subsequently blended with lamivudine, silicified microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide, aspartame, flavor and magnesium stearate, and compressed into a tablet using appropriate tooling.
EXAMPLE 5

(Example Removed)
PROCEDURE: A first granular portion was prepared by granulating a blend of microcrystalline cellulose and sodium starch glycolate with purified water, and drying the granules. A second granular portion was prepared by blending stavudine, microcrystalline cellulose and magnesium stearate, compacting the blend in a roller compactor and milling the compacts. The first and the second granular portions were subsequently blended with lamivudine, colloidal silicon dioxide, aspartame, flavor and magnesium stearate, and compressed into a tablet using appropriate tooling.
EXAMPLE 6

(Example Removed)
PROCEDURE: Microcrystalline cellulose and sodium starch glycolate were blended and granulated with water. The granules were blended with lamivudine and stavudine. The blend obtained was mixed with colloidal silicon dioxide, aspartame,
flavor and magnesium stearate; and was compressed into a tablet using appropriate tooling.
EXAMPLE 7

(Example Removed)
PROCEDURE: Microcrystalline cellulose and sodium starch glycolate were blended and granulated with water. The granules were blended with lamivudine, colloidal silicon dioxide, aspartame, flavor and magnesium stearate; and was compressed into a tablet using appropriate tooling.
The water-dispersibility of the compositions as described herein may be determined by evaluation of disintegration time. Thus, the tablets prepared as described in Examples 1 to 6 were evaluated for their disintegration time using conventional apparatus such as a USP disintegration apparatus. In such a procedure, the tablets are placed in water maintained at 37° C wherein the motion of the disintegration apparatus simulates the passage of a tablet through the body and the time required for each tablet to break down is noted. The disintegration time of tablets of Example 1 to 6 is given in Table 1.
TABLE 1: Disintegration time of tablets of Examples 1 to 6:

(Table Removed)
*as measured in a disintegration apparatus
The tablets as described in Examples 1 to 6 may be placed in 10 ml of water wherein the tablet will disintegrate and disperse within the time as described in Table 1 to give a visually uniform dispersion.
While several particular forms of the inventions have been described, it will be apparent that various modifications and combinations of the inventions detailed in the text can be made without departing from the spirit and scope of the inventions. Accordingly, it is not intended that the inventions be limited, except as by the appended claims.

WE CLAIM:
1) A water-dispersible pharmaceutical composition for oral administration comprising
one or more antiretroviral drugs and pharmaceutically acceptable excipients selected from a group comprising diluent, disintegrant, binder, lubricant and glidant.
2) The water-dispersible pharmaceutical composition according to claim 1, wherein
the composition comprises:
a) a combination of atleast two anti-retroviral drugs;
b) pharmaceutically acceptable excipients selected from a group comprising diluent, disintegrant, binder, lubricant and glidant.
3) The water-dispersible pharmaceutical composition according to claim 2, wherein
the composition comprises:
a) an intragranular portion comprising pharmaceutically acceptable excipients selected from a group comprising diluent, disintegrant, binder, lubricant, glidant and optionally atleast one anti-retroviral drug; and
b) an extragranular portion comprising pharmaceutically acceptable excipients selected from a group comprising diluent, disintegrant, lubricant, glidant and optionally atleast one anti-retroviral drug.

4) The water-dispersible pharmaceutical composition according to claims 1 and 2, wherein the antiretroviral drug is selected from a group comprising of lamivudine, stavudine and nevirapine.
5) The water-dispersible pharmaceutical composition according to claims 1 and 2, wherein the diluent is selected from a group comprising of lactose, dextrose, sucrose, fructose, maltose, powdered cellulose, microcrystalline cellulose, mannitol, erythritol, sorbitol, xylitol lactitol, dicalcium phosphate, tribasic calcium phosphate, calcium sulphate, calcium carbonate, and mixtures thereof.
6) The water-dispersible pharmaceutical composition according to claims 1 and 2, wherein the disintegrant is selected from a group comprising of sodium starch glycolate, cross-linked carboxymethylcellulose and its sodium salt, cross-linked polyvinylpyrrolidone, pregelatinised starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, alginates and its salts, and mixtures thereof.
7) The water-dispersible pharmaceutical composition according to claims 1 and 2, wherein the binder is selected from a group comprising of corn starch, pregelatinised starch, polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxyvinyl polymers, acrylates, and mixtures thereof.
8) The water-dispersible pharmaceutical composition according to claims 1 and 2, wherein the lubricant is selected from a group comprising of talc, magnesium stearate, zinc stearate, calcium stearate, sodium stearyl fumarate, stearic acid, and mixtures thereof.
9) The water-dispersible pharmaceutical composition according to claims 1 and 2, wherein the glidant is selected from a group comprising of talc, colloidal silicon dioxide, and mixtures thereof.
10)The water-dispersible pharmaceutical composition according to any of the claims 1 to 9, wherein the pharmaceutical composition is a tablet.
11)A process for the preparation of a water-dispersible pharmaceutical composition for oral administration, wherein the process comprises:
a) preparing a blend of one or more of pharmaceutically acceptable excipients selected from a group comprising diluent, disintegrant, binder, lubricant, glidant and optionally an anti-retroviral drug;
b) granulating the blend of step (a);
c) blending the granules obtained in step (b) with one or more of pharmaceutically acceptable excipients selected from a group comprising diluent, disintegrant, lubricant, glidant, and at least one anti-retroviral drug; and
d) processing the blend of step (c) into a pharmaceutical composition.
12) A water-dispersible pharmaceutical composition and process for its preparation as substantially exemplified and described herein.