FORM - 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE

(See section 10 and rule 13)
COMBINATION TABLET FOR THE TREATMENT OF AIDS
EMCURE PHARMACEUTICALS LTD.,
an Indian Company
of Emcure House, T-184, M.I.D.C, Bhosari, Pune 411 026,
Maharashtra, India,
THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED:

FIELD OF INVENTION
This invention relates to a combination therapy for treatment of AIDS.
INTRODUCTION
Antiretroviral therapy is the main treatment for Human Immunodeficiency Virus (HIV) or Acquired Immuno-Deficiency Syndrome (AIDS). In this therapy, a person needs to take at least two and preferably three drugs at the same time. This is because if only one drug is taken, the person might become resistant to the drug within a short span itself. Several drugs of different categories taken together lengthen the time taken by a person to become resistant to the drugs.
More than 20 anti-retroviral drugs have been approved for use in HIV-infected adults and adolescents. These drugs fall into several major classes:
1. Nucleoside/tide Reverse Transcriptase Inhibitors (NRTIs), which include abacavir (Ziagen), lamivudine, 3TC (Epivir), tenofovir (Viread), abacavir/lamivudine/zidovudine (Trizivir), lamivudine / zidovudine (Combivir), stavudine, d4T (Zerit), didanosine, ddl (Videx, Videx EC), zalcitabine, ddC (HIVID), and zidovudine, AZT (Retrovir).
2. Non-nucleoside Reverse Transcriptase Inhibitors (NnRTIs), which include delavirdine (Rescriptor), efavirenz (Sustiva), and nevirapine (Viramune).
3. Protease Inhibitors (PIs), which include amprenavir (Agenerase), nelfinavir (Viracept), saquinavir (Fortavase), indinavir (Crixivan), ritonavir (Norvir), saquinavir (Invirase), and lopinavir/ritonavir (Kaletra).
Unfortunately, antiretroviral drugs do not result in complete reconstitution of the immune function. Moreover, inhibition of viral replication by these agents is temporary, due to the evolution of resistant strains of virus that can grow in the presence of the antiretroviral agents. Monotherapy with these currently available antiretroviral drugs is hence not recommended.
Antiretroviral therapy, which typically involves combinations of various antiretroviral drugs, is now the standard of care for people with HIV. It is sometimes called HAART
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(Highly Active Anti-Retroviral Therapy). Studies clearly show that three-drug combinations of these anti-HIV drugs are much more effective than one drug used alone or two-drug combinations in preventing disease progression and death. Numerous studies of triple drug combinations using either a PI or an NnRTI with two NRTI anti-HIV drugs show that the triple combination could greatly reduce disease progression and deaths in people with AIDS.
The combination of drugs taken at the time of beginning the treatment is called the 'first-line treatment'. WHO recommends a standard first line treatment for all AIDS patients. This standardized regimen is an essential component of the so called "3-by-5" regimen which consists of:
a thymidine analog nucleoside reverse transcriptase inhibitor (NRTI) [stavudine (d4T) or zidovudine (ZDV)], a thiacytidine NRTI [lamivudine (3TC)] and
a non-nucleoside reverse transcriptase inhibitor (NNRTI) [nevirapine (NVP) or efavirenz (EFV).
However, antiretrovirals should not be combined abruptly due to overlapping toxicities and potential viral antagonism. Viral Antagonism or Overlapping Toxicity is shown in combinations of Stavudine + Zidovudine; Stavudine + Zalcitabine and Didanosine + Zalcitabine.'
Further, certain combination are devoid of adequate efficacy and hence are not acceptable such as combinations of Abacavir + Lamivudine (or Emtricitabine) + Tenofovir Didanosine + Lamivudine (or Emtricitabine) + Tenofovir.
Such combinations are therefore not useful.
Stavudine (Formerly called d4T) is a synthetic thymidine nucleoside analogue active
against the Human immunodeficiency Virus (HIV). Its chemical name is 2', 3'-
didehydro-3' -deoxythymidine
Stavudine inhibits replication of HIV in human cells. Antiretroviral activity is
dependent on phosphorylation by cellular kinases stavudine triphosphate. Once in the
active form stavudine inhibits HIV reverse transcriptase by competing with the natural
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substrate deoxythymidine triphosphate and by its incorporation into viral DNA causing a termination of DNA elongation. Stavudine inhibits DNA elongation, because it lacks an essential 3'-OH group. Stavudine triphosphate also inhibits cellular DNA polymerase beta and gamma and reduces the synthesis of mitochondrial DNA.
Stavudine is rapidly absorbed following oral administration. Mean absolute bioavailability ranges from 78 % to 86 %. It distributes equally between red blood cells and plasma. Stavudine crosses the blood brain barrier and distributes into cerebrospinal fluid. Protein binding of stavudine is negligible. The mechanism for metabolism in humans has not been elucidated, but it may be due to stavudine being cleaved to thymine, and subsequently used or eliminated. Non-renal clearance accounts for approximately 50 % of an oral dose, regardless of route of administration. Terminal half-life following oral administration is about 1/4 .The intracellular half-life of stavudine triphosphate is 3.5 hours. Excretion is about 40% renal via tubular secretion and glomerular filtration. Renal insufficiency prolongs the terminal elimination half-life up to as much as 8 hours.
Lamivudine (-)-l-[(2R, 5S)-2(Hydroxymethyl-l, 3-oxathiolan-5-yl] cytosine is synthetic nucleoside analogue used as an antiviral agent in the treatment of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections.
Lamivudine is reverse transcriptase inhibitor. It has been shown to inhibit both type 1 & type 2 HIV reverse transcriptase. Lamivudine can also inhibit replication of hepatitis B virus (HBV) because this replication depends on reverse transcription of an intermediate RNA to a minus strand DNA, which then serves as the template for synthesis of the plus-strand DNA. Intracellular phosphorylation of lamivudine produces the 5'-triphosphate metabolite (L-TP) in vitro. This active metabolite inhibits reverse transcriptase & viral DNA synthesis. L-TP also inhibits cellular DNA polymerase.
Lamivudine oral absorption is rapid, with a mean absolute bioavailability of 68% for the tablet. Food has no significant effect on systemic exposure to lamivudine. AUC and Cmax increase in proportion to oral dose over the range from 0.25 - 10 mg/kg. Lamivudine distributes into extravascular spaces. Lamivudine was found to penetrate into the cerebrospinal fluid (CSF) in children; CSF concentrations ranged from 5.6 -
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30.9 % of the concentration in a simultaneous serum sample. Plasma protein binding is less than 36%. Intracellular^ lamivudine is phosphorylated to its active 5'-triphosphate metabolite (L-TP), which has an intracellular half-life 10.5 - 15.5 hours. Hepatic metabolism is a minor route of elimination for lamivudine. The mean elimination half-life after single dose of Lamivudine ranges 5-7 hours.
Fixed dose combinations of three commonly known antiretrovirals, Lamivudine & Stavudine with or without Nevirapine are currently available in the market. However, these 3-in-l Fixed Dose Compositions are associated with many drawbacks, which need to be alleviated. These drawbacks are as follows:
1. Fixed Dose Combinations are particularly cautioned against use in patients who are
initiating therapy with nevirapine. Such compositions come with a caution statement
that they should not be administered to patients who have just initiated a therapy with
nevirapine. This is because; the recommended dose of Nevirapine varies depending
upon the stage of treatment. Importantly, the recommended dose of nevirapine, during
the initiating phase of the treatment is only one 200 mg tablet per day. This dosage must
not be exceeded under normal circumstances. This is essentially because, the drug
causes a severe rash in the first few weeks of treatment in around 7% of people who
take it and a small proportion develop serious, potentially life threatening liver
toxicities. Hence a lead in period must be followed religiously for the first 14 days of
therapy. A lead dose has been found to lessen the frequency of rash development and
other associated side effects. Following this lead-in dose, a dose escalation
(maintenance dose) nevirapine b.d. may be carried out in the absence of any
hypersensitivity reaction
Each tablet of a fixed dose combination of nevirapine + stavudine + lamivudine, to be taken twice daily, contains 200 mg of nevirapine. Hence such a combination is essentially not recommended for patients initiating the three-drug therapy.
2. Overdose of nevirapine in case of unmonitored administration of an FDC.
There is no antidote known, for a nevirapine overdose. Roughly 16% of people starting Nevirapine get a rash in the form of red blotches, itchy lumps or speckles on the skin. This rash usually appears after one to four weeks of treatment. In most cases the rash goes away after two to four weeks on the drug, and thereafter most people experience very few or no side effects. The rash can be treated in many cases with anti-histamines.
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However about 7% of people taking Nevirapine develop a more serious rash which can
occasionally require hospitalisation This rash usually goes away upon discontinuing the
drug, but one patient needed a skin graft.
Starting Nevirapine at a low dose and building up to the standard dose after two weeks
seems to reduce the risk of Nevirapine-related rash.
So it is recommended that people starting this combination should not begin treatment
straight away with triple drug combination, because it contains the full dose of
Nevirapine. Instead treatment should begin with Nevirapine once daily as a separate
tablet for first 14 days. After 14 days it can be started as a part of fixed drug
combination to be given twice daily.
3. Toxicity management of nevirapine in the fixed dose composition becomes very
difficult, more so because the physicians themselves find it hard to diagnose as to which
of the active drug is causing side effect.
4. Further, in a three in one fixed dose combination, dosage of nevirapine cannot be adjusted as per requirement and stage of treatment. The patient must therefore switch over to a two-drug combination or take the three drugs separately. Such regimens are not preferred as they are difficult to adhere to.
5. Fixed dose combinations offer no solution as far as paediatric administration is concerned.
6. Determination of the differential half-lives of drugs when treatment is interrupted becomes much more difficult and tedious in three-in -one FDCs.
So there is need for a formulation that provides Stavudine & Lamivudine in a single tablets, to be presented in a kit form together with Nevirapine , so that it is useful from the point of view of patient convenience. The best solution should be starter packs in which two different fixed dose combinations with or without Nevirapine are presented as the morning and evening pills. A patient compliant combination which while providing a three drug therapy not just limits the concentration of nevirapine present to that of a lead in dose but also offers an easily accessible risk management, particularly of nevirapine, is the need of the hour.
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OBJECT OF THE INVENTION
The object of the invention is to provide a process for the preparation of a fixed dose composition of stavudine and lamivudine either to be used alone or to be included in a kit containing all three drugs..
Yet another object of the invention is to provide a combination therapy comprising a fixed dose composition of stavudine and lamivudine, alone or co-packaged with nevirapine composition in a co-blister pack.
In particular, the object of the invention is to provide a more patient compliant combination therapy comprising a fixed dose composition of stavudine and lamivudine, co-packaged with nevirapine composition in a co-blister pack.
DESCRIPTION OF THE FIGURES
Figure 1 is a graph showing the Comparative Dissolution of Emduo (Combination of
Stavudine and Lamivudine as per the instant invention) with Zerit (Stavudine) and
Epivir (Lamivudine).
Figure 2 is a graph showing the Comparative Dissolution of Lamivudine (Emduo) with
Lamivudine (Epivir).
Figure 3 is a graph showing the Comparative Dissolution of Stavudine (Emduo) with
Stavudine (Zerit).
DETAILED DESCRIPTION
Treatment with stavudine and lamivudine combination has been found to be as effective as zidovudine and lamivudine combination (combivir) in reducing virus load although both combinations, without inclusion of nevirapine in the therapy, are sub optimal. WHO guidelines suggest a substitution of stavudine with zidovudine in case of intolerance to the latter and vice versa. However, stavudine is favored as the chosen nucleoside for the majority of patients in ART programs (in settings with severe resource limitations) because of lesser need for initial laboratory monitoring.
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Amongst the clinically effective and safe two-drug combination therapies, stavudine and lamivudine combination is categorized as an "alternative" dual NRTI backbone for initial therapy. In case of late virologic failure during a salvage therapy Stavudine needs to be combined with lamivudine with which it is synergistic.
Combination therapy is essential for the treatment of HIV/AIDS. At least three active drugs, usually from two different classes, are required to suppress the virus, allow recovery of the immune system, and reduce the emergence of HIV resistance. Co-packaged drugs (such as blister packs) or FDCs facilitate distribution and improve patient adherence.
Nevirapine + stavudine + lamivudine combination therapy is a well-established and accepted therapy for the treatment of AIDS. However, the therapy comes with an essential caution statement relating to the dosage and administration of nevirapine that Nevirapine is to be administered once daily for the first two weeks followed by twice daily. Therefore, for the first two weeks, one could not administer the triple-regimen as a single FDC.
This invention envisages a process for making a single tablet of stavudine 30/40 mg &
Lamivudine 150 mg. to be included in a kit Each kit contains:
PART A: 2 tablets of Stavudine 30/40 mg & Lamivudine 150 mg tablets
PART B: 1 tablet of Nevirapine 200 mg tablets.
Compositions of the invention containing excipients can be prepared by as exemplified
below:
For the combination tablet of stavudine and lamivudine

S.No Excipient Range (%)
1 Disintegrant 0.5-10%
2 Binder 1 - 75%
3 Wetting agent Not more than 5%
4 Diluent 5 - 95%.
5 Glidant 0.05 - 0.5%
6 Antiadherent 0.25 - 5%
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Procedure for the formation of combination tablet of stavudine and lamivudine
The process for preparation of Stavudine extended release tablet as per the invention
involves the following steps:
Step I. Sifting: Stavudine and lamivudine along with all excipients is sifted individually.
Step II. Preparation of a mix A blend of stavudine and lamivudine along with all the
sifted excipients except lubricants is prepared.
Step III. Granulation Blended mass was granulated with a suitable solvent for example
water.
Step IV. Wet mass milling: Step (III) wet mass is passed through multimill
Step V. DryingStep (IV) wet mass is dried at temperature of between 60°C to 70°C
Step VI. Lubrication:Step (V) granules are lubricated with lubricants, which had earlier
been sifted
Step VII. Compression
Step (VI) lubricated granules are compressed into tablets.
The tablets of the combination tablet of stavudine and lamivudine prepared as per the method disclosed herein show an immediate release profile. The profile shown by the tablets so formed [Emduo] is comparable with the dissolution profile shown by the marketed preparations of stavudine (Zerit) and lamivudine (Epivir). For better clarification the individual profiles of lamivudine (in Emduo) is separately compared with the marketed preparation, Epivir. Similarly, Emduo (stavudine) has been compared with the marketed preparation, Zerit separately. Table 1

Time Zerit Epivir Emduo Emduo
Minues Stavudine Lamivudi ne Stavudin e Lamivudine
0 0 0 0 0
5 57.93 79.83 76.68 80.98
10 83.21 88.86 93.68 99.29
20 89.22 91.85 95.8 101.85
30 92.16 94.87 95.49 101.86
45 93.56 95.12 95.44 102.49
60 94.68 96.97 96.33 103.68
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The invention is described in detail herein below with respect to the following examples, which are provided merely for illustration and are not intended to restrict the scope of the invention in any manner. Any embodiments that may be apparent to a person skilled in the art are deemed to fall within the scope of the present invention. Tables provide a summary of release pattern obtained over a period of 60 minutes using the composition of the present invention. These examples also state the best-preferred embodiments of the invention.
Formula:
Example 1
tablets of Stavudine 30/40 mg & Lamivudine 150 mg tablets
Active ingredient: Stavudine..30/40 mg
Lamivudine.... 150 mg
Excipients:
Maize Starch IP 27.38%
Microcrystalline cellulose IP 24.76 %
Pregelatinized starch 1.19%
Sodium starch glycolate 2.38 %
Colloidal silicon dioxide 0.714 %
Magnesium stearate 0.714 %
Purified water q.s.
Formulation Procedure:
Step I: Stavudine, Lamivudine, starch, Microcrystalline cellulose & Pregelatinized
starch were dry mixed.
Step II: Wet Granulation with starch paste.
Step III: Lubrication with colloidal silicon dioxide, Sodium starch glycolate & Magnesium stearate. Compression into tablet
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Example 2
tablets of Stavudine 30/40 mg & Lamivudine 150 mg tablets
TABLE 2

S.No. Ingredients Qty/tab [mg]
1 Lamivudine 150
2 Stavudine 40
3 Maize Starch 105
4 AvicelpH 101 104
5 Pregelatinized Starch (Starch 1500)
6 Pregelatinized Starch [Fully pregelatinized starch 78-1551) 5
7 Sodium Starch Glycolate (Primogel) 10
8 Colloidal Silicon Dioxide 3
9 Magnesium Stearate 3
10 Purified water
Tablet weight 420
Formulation Procedure: Step I. Sifting:
Stavudine and lamivudine along with all excipients is sifted. Step II. Preparation of a mix
A blend of stavudine along with all the sifted excipients except lubricants is prepared. Step III. Granulation
Blended mass was granulated with a suitable solvent for example water. Step IV. Wet mass milling:
Step (III) wet mass is passed through multimill Step V. Drying
Step (IV) wet mass is dried at temperature of between 60 °C to 70 °C Step VI. Lubrication:
Step (V) granules are lubricated with lubricants, which had earlier been sifted Step VII. Compression
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Step (VI) lubricated granules are compressed into tablets Dissolution Profile Table 3

Dissolution Stavudine (Emduo) Lamivudine (Emduo)
5 min 22.44 22.61
10min 40.74 41.2
20 min 64.83 65.82
30 min 80.16 81.67
45 min 88.01 90.19
60 min 97.14 97.34
Example 3 tablets of Stavudine 30/40 mg & Lamivudine 150 mg tablets

S.No. Ingredients Qty/tab [mg]
1 Lamivudine 150
2 Stavudine 40
3 Maize Starch 90
4 Avicel Ph l0l 94
5 Crosscarmellose Sodium 20
6 Sodium Lauryl Sulphate 10
7 Crosscarmellose Sodium 10
8 Colloidal Silicon Dioxide 3
9 Magnesium Stearate 2
10 Purified water qs
Tablet weight 419
Formulation Procedure same as in example 1: Dissolution Profile
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Table 4

Dissolution Stavudine Lamivudine
5 min 41.46 41.66
10min 74.95 75.43
20 min 91.63 92.47
30 min 88.96 90
45 min 91.27 92.15
60 min 90.02 92.93
Example 4
tablets of Stavudine 30/40 mg & Lamivudine 150 mg tablets

S.No. Ingredients Qty/tab [mg]
1 Lamivudine 150
2 Stavudine 40
3 Maize Starch 85
4 Avicel pH l01 94
5 Crosscarmellose Sodium 20
6 Sodium Lauryl Sulphate 10
7 Crosscarmellose Sodium 10
8 Maize Starch 5
9 Colloidal Silicon Dioxide 3
10 Magnesium Stearate 3
11 Purified water qs
Tablet weight 420
Formulation Procedure: same as in example 1 Dissolution Profile
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Table 5

Dissolution Stavudine Lamivudine
5 min 38.15 37.24
10min 68.6 67.81
20 min 88.21 88.28
30 min 89.91 90.11
45 min 90.16 90.7
60 min 89.19 90.04
Example 5
tablets of Stavudine 30/40 mg & Lamivudine 150 mg tablets

S.No. Ingredients Qty/tab [mg]
1 Lamivudine 150
2 Stavudine 40
3 Maize Starch 85
4 Avicel pH l0l 94
5 Crosscarmellose Sodium 20
6 Sodium Lauryl Sulphate 10
7 Crosscarmellose Sodium 10
8 Pregelatinized Starch (Starch 1500) 5
9 Colloidal Silicon Dioxide 3
10 Magnesium Stearate 3
11 Purified water qs
Tablet weight 420
Formulation Procedure: same as in example 1 Dissolution Profile
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Table 6

Dissolution Stavudine Lamivudine
5 min 42.74 42.45
10min 69.04 69.38
20 min 83.2 83.75
30 min 86.08 86.85
45 min 87.22 88.21
60 min 87.86 89.26
Example 6
tablets of Stavudine 30/40 mg & Lamivudine 150 mg tablets

S.No. Ingredients Qty/tab [mg]
1 Lamivudine 150
2 Stavudine 40
3 Maize Starch 85
4 Avicel Ph l0l 94
5 Sodium Lauryl Sulphate 10
6 Maize Starch 5
7 Sodium Starch Glycolate (Primogel) 30
8 Colloidal Silicon Dioxide 3
9 Magnesium Stearate 3
10 Purified water qs
Tablet weight 420
Formulation Procedure: same as in example 1 Dissolution Profile
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Table 7

Dissolution Stavudine Lamivudine
5 min 33.49 35.93
10min 56.56 61.65
20 min 78.42 86.48
30 min 82.56 91.25
45 min 83.78 92.83
60 min 83.53 92.9
Example 7
tablets of Stavudine 30/40 mg & Lamivudine 150 mg tablets

S.No. Ingredients Qty/tab [mg]
1 Lamivudine 150
2 Stavudine 40
3 Maize Starch 96.5
4 Avicel pH l0l 96.5
5 Crosscarmellose Sodium 3
6 Sodium Lauryl Sulphate 12
7 Crospovidone [Polyplasdone XL 10] 3
8 Crospovidone [Polyplasdone XL 10] 7
9 Crosscarmellose Sodium 7
10 Colloidal Silicon Dioxide 3
11 Magnesium Stearate 2
12 Purified water qs
Tablet weight 420
Formulation Procedure: same as in example 1 Dissolution Profile
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Table 8

Example 8

Dissolution Stavudine Lamivudine
5 min 41.19 41.38
10min 72.79 73.33
20 min 96.04 97.01
30 min 99.43 100.68
45 min 101.94 103.48
60 min 102.23 104.23

tablets of Stavudine 30/40 mg & Lamivudine 150 mg tablets

Dissolution Profile Table 9

S.No. Ingredients Qty/tab [mg]
1 Lamivudine 150
2 Stavudine 40
3 Maize Starch 86.5
4 Avicel pH l0l 90.5
5 Crosscarmellose Sodium 20
6 Sodium Lauryl Sulphate 12
7 Crosscarmellose Sodium 15
8 Colloidal Silicon Dioxide 3
9 Magnesium Stearate 3
10 Purified water qs
Tablet weight 420

Dissolution Stavudine Lamivudine
5 min 76.78 80.98
10 min 93.68 99.29
20 min 95.8 101.85
30 min 95.49 101.86
45 min 95.44 102.49
60 min 96.33 103.68
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Example 9
tablets of Stavudine 30/40 mg & Lamivudine 150 mg tablets

S.No. Ingredients Qty/tab [mg]
Lamivudine IP 150.00
Stavudine IP 30.00
Maize Starch IP 96.000
Microcrystalline cellulose IP [Avicel PH l0l] 90.50
Sodium Lauryl Sulphate IP 12.000
Croscarmellose Sodium USPNF 20.000
Colour Lake of Quinoline Yellow 0.500
Purified Water IP Qs
Croscarmellose Sodium USPNF 15.000
Colloidal Silicon Dioxide IP 3.00
Magnesium Stearate IP 3.00
Tablet weight 420
Formulation Procedure: same as in example 1
Comparative profile of Epivir (marketed composition of lamivudine individually) and Zerit (marketed composition stavudine individually) with lamivudine and stavudine as in the combination showing an equivalent and desired dissolution for an immediate release.
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Table 10

Time Zerit Epivir Emduo Emduo
Min Stavudine Lamivudine Stav Lam
0 0 0 0 0
5 57.93 79.83 76.68 80.98
10 83.21 88.86 93.68 99.29
20 89.22 91.85 95.8 101.85
30 92.16 94.87 95.49 101.86
45 93.56 95.12 95.44 102.49
60 94.68 96.97 96.33 103.68
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We Claim:
1. A single tablet dosage form of a synergistic fixed dose composition of stavudine and lamivudine in combination containing 30/40 mg & Lamivudine 150 mg.
2. A blister packaging, wherein tablets according to claim 1 are present in the form of a kit in a co-blister strip, as two tablets of stavudine and lamivudine combination and one tablet of Nevirapine sufficient for a daily dose.
3. A blister packaging, wherein the tablets are present in the form of seven kits as in claim 2, in a blister strip, sufficient for a weekly dose.
4. A tablet composition as in claim 1 , which further comprises disintegrant, preferablty at least one of sodium starch glycolate, croscarmellose sodium, and crospovidone, the mass of the disintegrant ranging from about 0.5 % to about 10 % of the total mass of the tablet; a binder preferably at least one of pregelatinized starch, hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, and gum arabic, the mass of the binder ranging between 1 - 75% of the total mass of the tablet; a wetting agent, typically sodium lauryl sulfate the mass of the wetting agent being not more than 5% of the total mass of the tablet, a diluent preferably at least one of lactose, mannitol, potato starch, wheat starch, rice starch, corn starch, and crystalline cellulose , the mass of the diluent ranging between 5 - 95% of the total mass of the tablet , a glidant, typically colloidal silicon dioxide the mass of the glidant ranging between 0.05 - 0.5% of the total mass of the tablet, lubricants, fluidizers preferably at least on of hydrous silica, light anhydrous silicic acid, and dried aluminium hydroxide gel, colorants, surfactants preferably at least one of sodium lauryl sulfate sucrose fatty acid ester, coating agents preferably at least one of zein, hydroxypropyl methylcellulose, and hydroxypropylcellulose .and antiadherent preferably at least one of stearic acid, calcium stearate, magnesium stearate, talc, magnesium meta-silicate aluminate, calcium hydrogen phosphate, and anhydrous calcium hydrogen phosphate the mass of the antiadherent ranging between 0.25 - 5% of the total mass of the tablet.
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5. A process for preparing a tablet as claimed in claim 1 comprising the steps of
sifting predetermined mass of Stavudine and Lamivudine, disintegrant, binder, wetting
agent, diluent, glidant, fluidizers and surfactants to obtain a sifted mixture;
blending the sifted mixture to obtain a blended sifted mixture;
preparing a dough of the blended sifted mixture with granulating fluid and forming wet
granules typically by wet mass milling;
drying the wet granules to obtain dried granules;
lubricating the said granules by means of a lubricant to obtain lubricated granules
compressing the lubricated granules to form a tablet
6. A process as claimed in claim 5, wherein the granulating fluid is at least one pharmaceutically acceptable solvent selected from a group of solvents consisting of isopropyl alcohol and purified water.
7. A tablet composition substantially as herein described and illustrated with reference to the examples, tables graphs and figures.
8. A process for preparing the tablet composition substantially as herein described and illustrated with reference to the examples, graphs and figures.
Dated this 7th day of October 2005.

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ABSTRACT
Combination therapy for treatment of AIDS comprising a single tablet of stavudine and lamivudine.