FIELD OF INVENTION
The present invention relates to a solid dosage formulation and in particular to oral pharmaceutical solid dosage formulations for use in HIV therapy. It also discloses the processes to make the same. The invention has been developed primarily for use as a formulation for use in HIV therapy and will be described hereinafter with reference to this application. However, it will be appreciated that the invention is not limited to this particular field of use.
BACKGROUND OF THE INVENTION AND RELATED PRIOR ART
Any discussion of the prior art throughout the specification should in no way be considered as an admission that such pi'ior art is widely known or forms part of the common general knowledge in the field.
There are multiple solid dosage pharmaceutical formulations known for use in HIV treatment therapy. Specifically, Kaletra® is a formulation of two HIV protease inhibitors [Lopinavir and Ritonavir] in a single solid dosage formulation. Till recently, this formulation was available in a soft gel capsule, embodied in the patent US6458818 granted to Abbott. The patent covers a solution of Lopinavir and Ritonavir in a long chain fatty acid organic solvent. This soft gel formulation has been criticized due to stability problems and need for keeping the formulation in refrigerated condition.
Abbott has now introduced a new solid dosage tablet formulation for combined administration of Lopinavir and Ritonavir, instead of the earlier soft gel formulation. It has also filed patent applications related to this tablet formulation. For instance, WO2005039551 covers a combination of Lopinavir and Ritonavir in a water soluble polymer and surface active agent wherein the tablet is formulated by melt extrusion process.
US2005084529 covers solid dispersion of HIV protease inhibitor in a water-soluble polymer and surface active agent. The water-soluble polymer has a glass transition temperature (Tg) of at least about 50°C.

US2007249692 covers solid dispersion of a pharmaceutical compound in a water soluble carrier, and a crystallization inhibitor [a polymer]. Also disclosed are methods of making solid dispersion which demonstrate an inhibition of crystallization.
OBJECTS OF THE INVENTION
It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.
It is an object of the invention in its preferred form to provide a solid dosage formulation for administration of at least one anti-retro viral drug selected from the group of protease inhibitors or Nucleoside Reverse Transcriptase Inhibitor or Non-Nucleoside Reverse Transcriptase Inhibitor.
It is an object of the invention in i'ts preferred form to provide a solid dosage formulation for administration of a plurality of anti-retro viral drugs in a single formulation.
It is an object of the invention in its preferred form to provide a solid dosage formulation for administration of a plurality of protease inhibitors in a single formulation.
It is an object of the invention in its preferred form to provide a solid dosage formulation for administration of Lopinavir and Riton.avir in a single formulation.
SUMMARY OF THE INVENTION
According to the invention there is provided a solid dosage pharmaceutical formulation for use in HIV therapy comprising a solid dispersion of at least one HIV protease inhibitor in at least one pharmaceutically acceptable v^ater-soluble non-polymeric excipient and at least one pharmaceutically acceptable surface acdve agent. According to an aspect of the invention, process to make the solid dosage formulation is also provided.

DETAILED DESCRIPTION INCLUDING PREFERRED EMBODIMENTS OF THE INVENTION:
The solid dosage form of the present invention envisages a dispersion of at least one anti-retro viral drug in a pharmaceutically acceptable water-soluble non-polymeric excipient. The solid dosage form may also contain a plu-ality of anti-retro viral drugs. The anti-retro viral drugs may be selected from:
(2S, 3S, 5S)-2- (2, 6-Dimethylphenoxyacetyl)amino-3-hydroxy-5-[2S-(l-tetrahydro- pyrimid-2-onyl)-3-methylbutanoyl]amino, 1, 6-diphenylhexane (Lopinavir);
(2S,3S, 5S)-5- (N- (N- ((N-methyl-N- ((2-isopropyl- 4- thiazolyl) methyl) amino) carbonyl)-L-valinyl)amino-2- (N- ( (5-thiazolyl) methoxy-carbonyl) -amino) -amino-1, 6-diphenyl-3-hydroxyhexane (Ritonavir);
N-tert-butyl-decahydro-2- [2 (R) -hydroxy-4-phenyl-3 (S)- [ [N- (2-quinolylcarbonyl)-Lasparaginyl] amino] butyl]- (4aS, 8aS) -isoquinoline-3 (S) -carboxamide (Saquinavir); N- (2 (R)-hydroxy-l (S) -indanyl) -2 (R)-phenylmethyl-4 (S)-hydroxy-5- (1- (4- (3-pyridylmethyl) -2 (S)-N'- (t-butylcarboxamido)-piperazinyl))-pentaneamide (Indinavir); Nelfinavir, Atazanavir, Tipranavir, Palinavir, Amprenavir, Mozenavir, Palinavir, Fosemaprenavir, Darunavir, Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Zidovudine, Zalcitabine, Nevirapine, Delavirdine, Efavirenz and Tenofovir their pharmaceutically acceptable sahs could also be employed.
"Dispersion" defines a system in a solid state (as opposed to a liquid or gaseous state) comprising at least two components, wherein one component is dispersed evenly throughout the other component or components. For e>:ample, the active ingredient or combination of active ingredients is dispersed in a matrix comjmsed of the pharmaceutically acceptable water-soluble non-polymeric excipient(s) and pharmace;utically acceptable surface active agent(s).
The term "solid dispersion" encompasses systems having small particles, typically of less than 1 fim in diameter, of one phase dispersed in another phase. When said dispersion of the components is such that the system is chemically and physically uniform or homogenous throughout or consists of one phase (as defined in thermodynamics), such a solid dispersion will be called a "solid solution" or a "glassy solution". A glassy solution is a homogeneous, glassy

system in which a solute is dissolved in a glassy solvent. Glassy solutions and isolid solutions of HIV protease inhibitors are preferred physical systems. These systems do not contain any significant amounts of active ingredients in their crystalline or microcrystalline state, as evidenced by thermal analysis (DSC) or X-ray diffraction analysis.
The water soluble non-polymeric excipients used in this invention can be selected from but are not limited to lactose, maltose, dextrose, sucrose, fructose, non-polymeric carbohydrate, alpha-hydroxy acid, marmitol, sorbitol, xylitol, dicalcium phosphate, calcium sulfate, lactitol, glucose, marmitol, citric acid, succinic acid, tartaric acid and derivatives of the foregoing, or combinations thereof Sorbitol is the preferred water soluble non-polymeric excipient.
The term "pharmaceutically acceptable surface active agent" as used herein refers to a pharmaceutically acceptable non-ionic surface active agent In one embodiment, the dosage form comprises at least one surface active agent having a hydrophilic lipophilic balance (HLB) value of from about 4 to about 10, preferably from about 7 to about 9. Known surface active agents like polyethylene glycols, sucrose fatty acid esters, e.g. sucrose monostearate, sucrose distearate, sucrose monolaurate, sucrose dilaurate; or sorbitan fatty acid mono esters such as sorbitan monolaurate (Span® series) can be effectively employed.
Besides the surface active agent having an HLB value of from about 4 to about 10, the dosage form may comprise additional pharmaceutically acceptable surface active agent s such as polyoxyethylene castor oil derivates, e.g. polyoxyethyleneglycerol triricinoleate or polyoxyl 35 castor oil (Cremophor® series); or block copolymers of ethylene oxide and propylene oxide, also known as polyoxyethylene polyoxypropylene block copolymers or polyoxyethylene polypropylene glycol (Poloxamer® series, from BASF Wyandotte Corp.); or a mono fatty acid ester of polyoxyethylene (20) sorbitan (Tween® series). The sorbitan mono fatty acid esters are preferred, with sorbitan mono laurate and sorbitan monopalmitate being particularly preferred.
In one embodiment of the present invention, the solid dosage form comprises a solid dispersion of:

(2S,3 S, 5 S)-5-(N-(N-((N-methyl-N-((2"isopropyl-4-thiazolyI) methyl) amino) carbonyI)-L-valinyl)amino-2-(N-((5-thiazolyl) methoxy-carbonyl)-amino)-amino-l, 6-diphenyl-3-hydroxyhexane (ritonavir) and
(2S, 3S,5S)-2- (2, 6-Dimethylphenoxyacetyl) amino-3-hydroxy-5-pS-(l-tetrahydro-pyrimid-2-onyl)-3-methylbutanoyi] amino-1, 6-diphenylhexane (lopinavir); sorbitol; and a sorbitan fatty acid ester.
^ Additionally, at least one additi\'e selected from flow regulators, disintegrants, bulking agents and lubricants may be added to the solid dosage form. The above excipients are well known to a person skilled in the art of formulations and hence not discussed in detail.
The process for preparing the above solid dosage formulation can be described as follows:
i) preparing a homogeneous melt of at least one anti-retro viral drug such as a HIV protease inhibitor, water-soluble non-polymeric excipients (s) and surface active agent (s), and ii) allowing the melt to solidify to obtain a solid dispersion product.
iii) and additionally adding additives i;o the solid dispersion product and compressing solid dispersion product into a tablet.
In one of the preferred forms, the: solid dosage form consists:
a) (2S, 3 S, 5 S)-5-(N-(N-((N-methyl-N-((2-isopropyl-4-thiazolyl) methyl) amino) carbonyl) -L-valinyl)amino-2- (N- ((5-thia2olyl) methoxy-carbonyl)-amino)-amino-l, 6-diphenyl-3-hydroxyhexane (ritonavir)
b) and (2S, 3S, 5S)-2-(2, 6-Dimethylphenoxyacefyl) amino-3-hydroxy-5-[2S-(l-tetrahydro-pyrimid-2-onyl)-3-methylbutanoyl] amino-1, 6-diphenylhexane (lopinavir) present in an amount from about 4 % to about 20 % by weight of the dosage form;
c) sorbitol from about 60 % to about 80 % by weight of the dosage form;
d) and a sorbitan fatty acid ester from atiout 5 % to about 10 % bv weight of the dosage form.

Various methods can be used for manufacturing the solid dosage forms according to the invention. These methods comprise the preparation of a solid solution of the anti-retro viral drug such as HIV protease inhibitor or the combination of HIV protease inhibitors in a matrix of the water-soluble non-polymeric excipient and the surface active agent, and shaping into the required tablet form. Alternatively, the solid solution product may be subdivided to granules, e.g. by grinding or milling, and the granules may subsequently be compacted to tablets. Various techniques exist for preparing solid solutions including melt-extrusion, spray-drying and solution-evaporation. Melt granulation \vith solvent evaporation or solution evaporation being preferred processes.
The melt-extrusion process comprises the steps of preparing a homogeneous meU of the HIV protease inhibitor or the combination of HIV protease inhibitors, the water-soluble non-polymeric excipient and the surface active agent, and cooling the melt until it solidifies. "Melting" means a transition into a licjuid or rubbery state in which it is possible for one component to get embedded homogeneously in the other. Typically, one component will meh and the other components will dissolve in the melt thus forming a solution. Melting usually involves heating above the softening point of the water-soluble non-polymeric excipient. The preparation of the melt can take place in a variety of ways. The mixing of the components can take place before, during or after the fonnation of the melt. For example, the components can be mixed first and then melted or be simultaneously mixed and melted. Usually, the melt is homogenized in order to disperse the active ingredients efficiently.
Usually, the melt temperature is m the range of about 70 to about 250°C., preferably from about 80 to about 180°C., most preferrec[ from about 100 to about 140°C. The active ingredients can be employed as such or as a solution or dispersion in a suitable solvent such as alcohols, aliphatic hydrocarbons or esters. Another solvent which can be used is liquid carbon dioxide. The solvent is removed, e.g. evaporated, upon preparation of the melt. Various additives may be included in the melt, for example flow regulators such as colloidal silica; lubricants, fillers, disintegrants, plasticizers, stabilizers such as antioxidants, light stabilizers, radical scavengers, stabilizers against microbial attack.

The melting and or mixing takes place in an apparatus customary for this purpose. Particularly suitable ones are extruders or kneaders. Suitable extruders include single screw extruders, intermeshing screw extruders or else multi-screw extruders, preferably twin screw extruders, which can be co-rotating or counter-rotating and, optionally, be equipped with kneading disks. It will be appreciated that the working temperatures will also be determined by the kind of extruder or the kind of configuration within the extruder that is usedr
The melt ranges from pasty to vi scous. Shaping of the extrudate conveniently is carried out by a calender with two counter-rotating rollers with mutually matching depressions on their surface. A broad range of tablet forms can be attained by using rollers with different forms of depressions. Alternatively, the extrudai:e is cut into pieces, either before (hot-cut) or after solidification (cold-cut).
Optionally, the resulting solid solution product is milled or ground to granules. The granules may then be compacted. Compression of the powder mass is usually done in a tablet press, more specifically in a steel die between two moving punches. Where a solid dosage form of the invention comprises a combination of more than one anti retro viral drug (or a combination of an anti retro viral drug with one or more other active ingredients) it is of course possible to separately prepare solid solution products of the individual active ingredients and to blend the milled or ground products before compacting.
Dosage forms according to the invention may be provided as dosage forms consisting of several layers, for example laminated or multilayer tablets. They can be in open or closed form. "Closed dosage forms" are those in which one layer is completely surrounded by at least one other layer. Multilayer forms have the advantage that two active ingredients which are incompatible with one another can be processed, or that the release characteristics of the active ingredient(s) can be controlled. For example, it is possible to provide an initial dose by including an active ingredient in one of the outer layers, and a maintenance dose by including the active ingredient in the inner layer(s).

Multilayer tablets types may be produced by compressing two or more layers of granules. Alternatively, multilayer dosage forms may be produced by a process known as "co-extrusion". In essence, the process comprises preparation of at least two different melt compositions as explained above, and passing these molten compositions into a joint co-extrusion die. The shape of the co-extrusion die depends on the required drug form. For example, dies with a plain die gap, called slot dies, and dies with an annular slit are suitable.
Optionally, the compressed tablets can be film-coated. A film coat on the tablet further contributes to the ease with which it Ciin be swallowed. A film coat also improves taste and provides an elegant appearance. If desired, the film-coat may be an enteric coat. Inline with the disclosed invention, the' exemplary compositions are given below to further illustrate the invention without limiting it. These compositions are processed by solvent evaporation technique. The prepared tablets were coated with Opadry aqueous dispersion.
Although the invention has been described- with reference to specific examples, it will be appreciated by those skilled in the art that the invention may be embodied in other forms.
Example 1

S.N. Ingredient Mg /unit
1 Lopinavir 200.00
2 Ritonavir 50.00
3 Sorbitol 853.00
4 Sorbitan monolaurate (Span 20) 85.00
5 Colloidal Silic;on Dioxide 12.00
6 Sodium Stean/l Fumarate 8.00
7 Colloidal Silic;on Dioxide 12.00
Tablet Weight 1220.00
Brief Manufacturing Process
1. Dissolve Lopinavir and Ritonavir in ethanol.
2. Mix well Sorbitol, sorbitan monolaurate and colloidal silicon dioxide and add it to ethanol to prepare dispersion.
3. Add step no 1 solution to step no. 2 dispersion and mix well.

4. Evaporate the solvent of step no 3 to prepare a premix.
5. Mill the premix to obtain a suitable paiticle size distribution.
6. Sift sodium stearyl fumarate and colloidal silicon dioxide and add to the premix and blend.
7. Compress the blend of step no. 6 to prepare tablets.
8. Coat the tablets of step no. 7.
Example 2

S.N. Ingredient Mg /unit
1 Lopinavir 200.00
2 Ritonavir 50.00
3 Citric Acid Anhydrous 653.00
4 Sorbitan monolaurate (Span 20) 105.00
5 Colloidal Sili(;on Dioxide 15.00
6 Sodium Stearyl Fumarate 12.00
7 Colloidal Sili<;on Dioxide 15.00
Tablet Weight 1050.00
Brief Manufacturing Process
1. Mix well Lopinavir and Ritonavir.
2. Mix well citric acid anhydrous, sorbitan monolaurate and colloidal silicon dioxide and add it to dry mix of Lopinavir and Ritonavir.
3. Heat the mixture of step no. 2 to about 120 - 140°C to get a molten mass and cool it immediately to obtain a solid mass.
4. Mill the solid mass of step no. 3 to obtain a suitable particle size distribution.

6. Sift sodium stearyl fumarate and colloidal silicon dioxide and add to the premix and blend.
7. Compress the blend of step no. 6 to prepare tablets.
8. Coat the tablets of step no. 7.
Example 3

S.N. Ingredient Mg /unit
1 Lopinavir 100.00
2 Ritonavir 100.00
3 Sorbitol 773.00
4 Polyoxyethylene Glycerol Oxystearate 75.00

(Cremophore mi 40)
5 Colloidal Silicon Dioxide 15.00
6 Sodium Stear)'l Fumarate 22.00
7 Colloidal Silicon Dioxide 15.00
Tablet Weight 1100.00
Brief Manufacturing Process
1. Mix well Lopinavir and Ritonavir.
2. Mix well Polyoxyethylene Glycerol (Dxystearate, sorbitan monolaurate and colloidal silicon dioxide and add it to dry mix of Lopinavir and Ritonavir.
3. Heat the mixture of step no. 2 to about 120 - 140°C to get a molten mass and cool it immediately to obtain a solid mass.
4. Mill the solid mass of step no. 3 to obtain a suitable particle size distribution.

6. Sift sodium stearyl fumarate and colloidal silicon dioxide and add to the premix and blend.
7. Compress the blend of step no. 6 to pr<:pare tablets.
8. Coat the tablets of step no. 7.
Example 4

S.N. Ingredient Mg /unit
1 Ritonavir 100.00
2 Mannitol 773.00
3 Sorbitan monolaurate (Span 20) 59.00
4 Colloidal Silicon Dioxide 11.00
5 Sodium Steand Fumarate 16.00
6 Colloidal Silicon Dioxide 11.00
Tablet Weight 970.00
Brief Manufacturing Process
1. Mix well Ritonavir and mannitol.
2. Mix well sorbitan monolaurate and colloidal silicon dioxide and add it to dry mix of Ritonavir and mannitol.
3. Dissolve the mixture of step no. 2 in a mixture of water and ethanol.
4. Evaporate the step no. 3 solution to prepare a premix.
5. Mill the premix of step no. 4 to obtain a suitable particle size distribution.
6. Sift sodium stearyl fumarate and colloidal silicon dioxide and add to the premix and blend.

7. Compress the blend of step no. 6 to prepare tablets.
8. Coat the tablets of step no. 7.
Example 5

S.N. Ingredient Mg /unit
1 Lopinavir 200.00
2 Ritonavir 50.00
3 L-Tartaric Acid 877.00
4 Sorbitan monolaurate (Span 20) 75.00
5 Colloidal Silicon Dioxide 17.00
6 Sodium Stear^'l Fumarate 18.00
7 Colloidal Silic;on Dioxide 13.00
Tablet Weight 1250.00
Brief Manufacturing Process
1. Mix well Lopinavir and Ritonavir.
2. Mix well tartaric acid, sorbitan monolaurate and colloidal silicon dioxide and add it to dry mix
of Lopinavir and Ritonavir.
3. Heat the mixture of step no. 2 to about 140 - 160°C to get a molten mass and cool it immediately to obtain a solid mass.
4. Mill the solid mass of step no. 3 to obtain a suitable particle size distribution.

6. Sift sodium stearyl fumarate and colloidal silicon dioxide and add to the premix and blend.
7. Compress the blend of step no. 6 to prepare tablets.
8. Coat the tablets of step no. 7.
Example 6

S.N. Ingredient Mg /unit
1 Lopinavir 200.00
2 Ritonavir 50.00
3 Soy Lecithin 54.00
4 Sorbitan monolaurate (Span 20) 84.00
5 Polysorbate 80 100.00
6 Sorbitol 600.00
7 Colloidal Silicon Dioxide 12.00

8 Sodium Stearj'l Fumarate 12.00
9 Colloidal Silicon Dioxide 8.00
10 Croscarmellose sodium 40
Tablet Weight 1160.00
Brief Manufacturing Process
1. Mix sorbitol, soy lecithin and colloidal silicon dioxide (ingredient 7)) and heat till molten
mass is formed 2 Add Sorbitan monolaurate and Polysoibate 80 to the material of step 1
3. Add Lopinavir and Ritonavir to the m:ixture of step 2 and mix till uniform system is obtained..
4. Cool the material of step 3 and Mill the solid mass to obtain a suitable particle size distribution.
5. Sift sodium stearyl ftimarate, croscarmellose sodium and colloidal silicon dioxide and add to the mixture of step 4.
6. Compress the blend of step no. 5 to prepare tablets.
Dissolution Study:
The composition illustrated in example 1 was subjected to dissolution test in 900mL of 0.06M Polyoxyethylene 10 Lauryl Ether at 75FIPM,, Apparatus-II (Paddle). The dissolution profile was compared with Kaletra® Tablets 200/50 mg (Lopinavir/Ritonavir Tablets 200/50 mg, Manufactured and supplied by Abbott Laboratories Ltd.)

Time
(minutes) Kaletra® Tablets (Lot No. 3U069Y40) Example 1

Mean %RSD Mean %RSD
% Lopinavir released
10 15.3 14.2 11.6 15.2
20 33.2 11.2 28.9 12.1
30 50.9 iO.3 48.3 9.6
45 69.7 9.0 66.4 8.9
60 85.4 6.8 82.3 7.0
90 97.1 4.8 96.5 4.5
120 iOI.4 1.2 99.6 1.1
% Ritonavir released
10 15.0 14.2 16.1 13.2
20 32.7 11.2 33.1 10.9
30 50.3 9.S 54.7 8.7

We claim:
1. A solid dosage form comprising,
a) a solid dispersion of at least one anti r(;tro viral drug,
b) at least one water-soluble non-polymeric excipient,
c) at least one surface active agent and pharmaceutically acceptable excipients.

2. The solid dosage form of claim 1, wherein said anti retro viral drug is selected from a group consisting of; ( 2S,3S, 5S)-5- (N- (N- ((TSI-methyl-N- ((2-isopropyl- 4- thiazolyl) methyl) amino) carbonyl)-L-valinyl)amino-2- (N- ((5-thiazolyl) methoxy-carbonyl) -amino) -amino-1, 6-diphenyl-3-hydroxyhexane (ritonavir)i(2S, 3S, 5S)-2- (2, 6-Dimethylphenoxyacetyl)amino-3-hydroxy-5-[2S-(l-tetrahydro- pyrimid-2-onyl)-3-methylbutanoyl]amino, 1, 6-diphenylhexane (lopinavir);N- (2 (R)-hydroxy-l (S) -indjmyl) -2 (R)-phenylmethyl-4 (S)-hydroxy-5- (1- (4- (3-pyridylmethyl) -2 (S)-N'- (t-butylcarboxamido)-piperazinyl))-pentaneamide (indinavir); N-tert-butyl-decahydro-2- [2 (R) -hydroxy-4-phenyl-3 (S)- [ [N- (2-quinolylcarbonyl)-Lasparaginyl] amino] butyl]- (4aS, 8aS) -isoquinoline-3 (S) -carboxamide (saquinavir); 5 (S) -Boc-amino-4 (S) -hydroxy-6-phenyl-2 (R) phenylmethylhexanoyl- (L)-Val- (L)-Phemorpholin-4-ylamide or a combination thereof.
3. The solid dosage form of claim 1, comprising a plurality of anti retro viral drugs.
4. The solid dosage form of claim 1, wherein said non-polymeric excipient is selected from a group consisting of lactose, maltose, dextrose, sucrose, fructose, non-polymeric carbohydrate, alpha-hydroxy acid, mannitol, sorbitol, xylitol, dicalcium phosphate, calcium sulfate, lactitol, glucose, mannitol, citric acid, succinic acid, tartaric acid and derivatives of the foregoing, or combinations thereof.
5. The solid dosage form of Claim 1 wherein said pharmaceutically acceptable non-polymeric excipient is a sorbitol.
6. The solid dosage form of Claim 1 wherein said pharmaceutically acceptable surface active agent is a sorbitan fatty acid ester.

7. A solid dosage form comprising a solid dispersion of
(2S,3 S, 5 S)-5-(N-(N-((N-methyl-N-((2-isopropyl-4-thiazolyl) methyl) amino) carbonyl)-L-
valinyl)amino-2-(N-((5-thiazolyi)methoxy-carbonyl)-amino)-amino-l, 6-diphenyl-3-
hydroxyhexane (ritonavir) and
(2S, 3S,5S)-2- (2, 6-Dimethylphenoxyacetyl) amino-3-hydroxy-5-[2S-(l-tetrahydro-pyrimid-2-
onyl)-3-methy]butanoyl] amino-1, 6-diphenylhexane (lopinavir);
sorbitol; and
a sorbitan fatty acid ester.
8. The solid dosage form of Claim 1 or 7 containing at least one additive selected from flow regulators, disintegrants, bulking agents and lubricants.
9. Process for preparing a solid-dosage form comprises;
i) preparing a homogeneous melt of at least one anti retro viral drug, water-soluble non-polymeric excipients (s) and surface active agent (s), and ii) allowing said melt to solidify to obtain a solid dispersion product.
iii) and additionally adding additives to said solid dispersion product and compressing solid dispersion product into a tablet.
10. A solid dosage form comprising,
a) (2S, 3 S, 5 S)-5-(N-(N-((N-methyl-N-((2-isopropyl-4-thiazolyl) methyl) amino) carbonyl) -L-valinyl)amino-2- (N- ( (5-thiazolyi) mei;hoxy-carbonyl)-amino)-amino-l, 6-diphenyl-3-hydroxyhexane (ritonavir)
b) and (2S, 3S, 5S)-2-(2, 6-Dimethylphenoxyacety]) amino-3-hydroxy-5-[2S-(l-tetrahydro-pyrimid-2-onyl)-3-methylbutanoyl] am:ino-l, 6-diphenylhexane (lopinavir) present in an amount from about 4 % to about 20 % by weight of said dosage form;
c) sorbitol from about 60 % to about 80 % by weight of said dosage form;
d) and a sorbitan fatty acid ester from about 5 % to about 10 % by weight of said dosage form.