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N.Sureshbabu et al. / International Journal of Advances in Pharmaceutical Research 

IJAPR 

Available Online through 

www.ijapronline.org 

Research Paper 

ISSN: 2230 – 7583 

DEVELOPMENT OF FIXED DOSE COMBINATION OF ANTI-RETROVIRAL DRUGS 

CONTAINING LAMIVUDINE, NEVIRAPINE AND ZIDOVUDINE IN THE FORM OF 

A DISPERSIBLE TABLET FOR PEDIATRIC USE 

N.Sureshbabu* 1 , Dr.M.SenthilKumar 1 , Dr.V.Sreenivasulu 2 , S.Valarmathi 1 , S.Srinivas Naidu 1 , 

Kasam Naveen Kumar 3 , D.Hariharan 1 . 

1 Annai Veilankannie’s Pharmacy College, Chennai-17, India 

2 Sri Lakshmi Venkateswara Institute of Pharmaceutical Sciences, Prodduturu, A.P, India 

3 Department of Pharmaceutics, SLC’S College of Pharmacy, Hyderabad, India 

Received on 22 – 07 - 2012 Revised on 18 – 08- 2012 Accepted on 25– 08 – 2012 

ABSTRACT 

In AIDS therapy, mono therapy is not recommended because incomplete viral suppression can lead to development 

of resistance. Combinations of antiretrovirals create multiple obstacles to HIV replication to keep the number of 

offspring low and reduce the possibility of a superior mutation. The present investigation reports development of an 

in-vitro dispersible fixed dose combination tablet containing Lamivudine(30mg), Nevirapine(50mg) and 

Zidovudine(60mg). The dispersible tablet is intended for ease of administration, primarily to pediatric patients. The 

tablets were prepared by wet granulation techanique and evaluated for various parameters like weight variations, 

hardness, friability, disintegration time, assay, related impurities and dissolation profile. The optimized formulation 

contains 12% of Lamivudine, 20% of Nevirapine and 24% of Zidovudine as active ingredients, 24.8% of Lactose 

monohydrate and 8% of Microcrystalline Cellulose as diluent, 5.2% of Sodium Starch Glycolate as disintegrant, 

1.4% silicon dioxide as Glidant, 1.6% Sucralose as sweetener, 0.8% strawberry flavor 1% of povidone as binder 

and 1.2% of magnesium stearate as lubricant. The optimized formulation had a weight variation < 10%, hardness of 

35-50N, percentage friability of 0.15, disintegration time of 55-60 sec, % assay was 102.2% for Lamivudine, 

99.9% for Nevirapine and 102.5% for Zidovudine and in vitro drug release after 30mins was 100.2 % for 

Lamivudine, 99.9% for Nevirapine and 100.1% for Zidovudine. Tablets were packed in HDPE containers for 

stability study. The formulation was stable after three month of accelerated stability studies. 

Key Words: AIDS, HIV, Dispersible tablets, fixed dose combination, Lamivudine, Nevirapine, wet granulation, 

Zidovudine. 

INTRODUCTION 

The number of people living with HIV/AIDS has 

risen from around 8 million in 1990 to more than 33 

million and is still growing. More than 25 million 

people have died of AIDS since 1981 and there is no 

immediate cure to curb such untimely deaths. India 

has a population of more than one billion; around 

half of them are adults in sexually active group. 

Address for Correspondence 

N.Sureshbabu 

Department of Pharmaceutics 

Annai Veilankanni’s Pharmacy College 

Chennai-17 

Mail I d:sureshpharma2012@yahoo.com 

The first AIDS in India was detected in 1986, since 

then HIV infection has been reported all over the 

country. As of July 2011 revised estimate, now 3 

million people in India are living with AIDS 1 . 

During this decade, effective therapies aimed at 

continued suppression of HIV replication and 

targeted at resting HIV reservoirs such as brain, 

lymphatic systems will be critical to prolong survival 

and renewing hopes for a cure. Thus goals of 

antiretroviral therapy include, reducing the 

symptoms of HIV infection and delay disease 

progression to AIDS. Established HIV infection is 

diagnosed by finding antibodies to HIV in the 

plasma using various serological testing methods 

IJAPR / Sept. 2012/ Vol. 3 /Issue. 9 / 1116 – 1130 1116


such as ELISA, Orasure western blot, SUDS, 

Orasure HIV-1. Generally according to the United 

States Food and Drug Administration and World 

Health Organization guidelines, the antiretroviral 

therapy is commenced with these observations, such 

as when patients experience severe symptoms of 

HIV infection or have been diagnosed with AIDS or 

when the viral load in the blood sample is found to 

be 50,000 copies/ml or more or when the CD4 cell 

count is less than 200-350 cells/mm 3 . 1 

Antiretroviral drugs are broadly classified 

by the phase of the retrovirus life cycle that the drug 

inhibits 1,3,4 . 

‣ Nucleoside and nucleotide reverse 

transcriptase inhibitors(NRTI) inhibits 

reverse transcription by being incorporated 

into the newly synthesized viral DNA and 

thus preventing further elongation 

Examples: Abacavir, Emtricitabine, 

Tenofovir, Lamivudine, Didanosine, 

Stavudine, Zidovudine, Amdoxovir 

‣ Non nucleoside reverse transcriptase 

inhibitor (NNRTI) inhibits reverse 

transcriptase by directly binding to the 

enzymes and thus interferes with its 

function. Examples: Efavirenz, Nevirapine, 

Etravirine, Rilpivirine 

‣ Protease inhibitors (PI) targets viral 

assembly by inhibiting the activity of 

protease, an enzyme used by HIV to cleave 

nascent proteins for final assembly of new 

virons. Examples: Ritonavir, Saquinavir, 

Lopinavir, Fosamprenavir, Saquinavir, 

Atazanavi. 

‣ Integrase inhibitors (IT) inhibit the 

enzyme integrase, which is responsible for 

integration of viral DNA into the DNA of 

infected cell. Examples: Elvitegravir, 

Raltegravir. 

‣ Entry inhibitors or Fusion inhibitors (FI) 

interferes with binding, fusion and entry of 

HIV-1 to the host cell by blocking one of 

several stages. Examples: Maraviroc, 

Enfuvirtide, Vicriviroc 

Combination therapy 

Mono-therapy is no longer recommended because 

incomplete viral suppression can encourage 

development of resistance. Similarly, magnitude and 

durability of viral suppression is lower with dual 

antiretroviral combinations compared with 

combinations containing three or more agents. For 

example, generally two NRTIs are combined with 

antiretroviral from PI or NNRTI class. Similarly, 

mono-therapy with PI or NNRTI is also not 

advisable in order to prevent the emergence of 

resistance and subsequent drug failure. 

In the present study, a combination of Lamivudine 

/Nevirapine/Zidovudine (30mg/50mg/60mg) has 

been used to develop in vitro dispersible tablet for 

pediatrics use. Since the dose of three active 

ingredients was more, it is a challenge to 

successfully formulate an in- vitro dispersible tablet 

using limited choice and concentration of excipients. 

In the present study Lactose monohydrate and MCC 

was used as diluents, SSG used as disintegrant, 

Povidone as binder, Colloidal silicon dioxide as 

Glidant, Sucralose as sweetener, strawberry as flavor 

and Mg.St as lubricant. 7 

MATERIALS AND METHODS 

Lamivudine, Nevirapine, Zidovudine, Lactose 

monohydrate, MCC, SSG, Povidone, Colloidal 

silicon Di oxide, Strawberry flavour, Mg Stearate 

Procured from Alchem Murugan Suppliers Chennai. 

Preformulation 

The following are the preformulation studies 

conducted on the active pharmaceutical ingredients: 

‣ Description 

‣ Solubility 

‣ Identification by IR, HPLC, DSC 

The preformulation parameters considered for 

formulation aspects are: 

‣ Melting point 

‣ Bulk density 

‣ Tapped density 

‣ Particle size analysis 

‣ Drug-excipients compatibility studies 

Description 

Powder was assessed for color, odour, 

taste, hydroscopicity, etc. 

Solubility: The solubility studies were carried out 

for all the three API’s in distilled water and also with 

other solvents by adding excess amount of the drug 

in to the flask in each case and keeping the flask on a 

shaker. 

Identification by IR spectroscopy 

IR spectra of the pure drug taken in KBr at 

moderate scanning speed. 

Bulk density and Tapped density 

Bulk density (D b ) ═ Mass of the powder (M) / 

Bulk volume (V b ) 

Tapped density (D t ) ═ Mass of the powder (M) 

/ Tapped volume (V T ) 

The Carr ’ s index is the measure of propensity of the 

powder to be compressed. It is calculated using the 

formula given below. 

Carr ’ s index (CI) ═ (D t – D b ) / D t × 100 



Angle of repose 

It is the maximum angle possible between the 

surface of a pile of the powder and the horizontal 

plane. 

Tan θ =h/r 

Where, 

h = height in cms 

r = radius in cms 

Compatibility studies 

The drug and excipients were mixed as per table 4.4 

and were distributed equally in 10ml moulded glass 

vials with 20mm grey coloured rubber plugs. They 

were loaded for stability study at 25 ± 2 0 C / 60 ± 

5%RH and 40 ± 2 0 C / 75 ± 5% RH. The samples 

were drawn in the intervals of zero (initial) and 

fourth week and analyzed for drug stability by HPLC 

method. 

Precompression parameters: 

Following properties were evaluated as 

Precompression parameters 

‣ Loss on drying 

‣ Bulk density 

‣ Tapped density 

‣ Particle size distribution 

Compression parameters: 

Following parameters were evaluated during 

compression 

‣ Average weight 

‣ Hardness test 

‣ Friability test 

‣ Disintegration test 

‣ Dissolution 

Post compression parameters: 

Following parameters were evaluated as 

post compression parameters 

‣ Physical parameters like Bulk density, 

Tapped density and Carr’s index 

‣ Disintegration 

‣ Assay 

‣ Related substances 

‣ Dissolution 

Formulation development: 

RESULTS AND DISCUSSION 

Drug – Excipients compatibility studies were 

performed for a period of 4 weeks at 40±2 0 C/75±5% 

RH. The results showed that the impurities were 

found to be with in limit. The results are shown in 

Table 5.4. The impurities were compared with 

samples (Table 5.4), and found with in the limit. 

From this we can conclude that there was no 

interaction between lamivudine,nevirapine and 

zidovudine with selected excipients. 

‣ F-1 was dropped as poor flow 

properties, torrent sticking to 

punches. 

‣ Dispersion in the water is poor. 

‣ This (F-2) was formulation 

dropped as sticking problem was 

observed. 

‣ So wet granulation is selected for 

next formulation. 

In the third formulation F-3 (Table 4.9) the wet 

granulation was selected using Cros-povidone as a 

disintegrating agent, used both intra and extra 

granularly. The granulation was done using FBP. 

Dispersion in water was satisfactory and taste was 

bland. However, formulation F-3 was dropped as rat 

hole was observed during compression in hopper & 

slight sticking to lower punch. The fourth 

formulation F-4 (Table 4.9) wet granulation was 

done RMG using cross-povidone as disintegrating 

agent, in both intra and extra granulation process. 

The approach was dropped as flow of the granules 

was poor. So next formulation including excipients 

which increase flow. 

In the fifth formulation F-5(Table 4.10), 

povidone was used as a binder and CCS used as a 

binder. Flow property of granules was satisfactory 

and taste of dispersion was sweet so sucralose to be 

used for further batches. This formulation F-5 was 

dropped as after dispersion in water slight bigger 

granules settled at the bottom. So Polyplasdone Xl- 

10 used as a disintegrate in the next batch. 

The sixth formulation F-6(Table 4.11) the 

average weight of tablet was increased to 250mg 

from 220mg using lactose monohydrate as a diluent 

and Polyplasdone Xl-10 used as disintegrant, 

granulation was done in RMG. Granules flow was 

satisfactory so granulation was carried out in RMG 

was further batch. Dispersion in water gave 

flavoured, sweet taste strawberry flavour was used 

for further batch. Few granules were retained after 

pouring on 30# mesh. The weight of tablet increased 

to 250mg for further batch this approach was 

dropped as rat hole in the hopper is observed and 

sticking to lower punch is observed. 

The seventh formulation F-7 (table 4.12) 

was by changing the disintegrate (SSG) used, 

dispersion in water is good it took 1 min disintegrate 

in water and dispersion passing through #30 mesh. 

Dispersion in water gave flavoured, sweet taste and 

flow of granules is good. The stability data for 3 

moths studied the amount of impurity within the 

limit and drug release is more 80% within 15 min. so 

this batch is optimized. 

Post compression parameters of F-7 were as 

follows, 

Average weight: The average weight of the tablet 

was 250 mg. 

Thickness: The thicknesses of the tablets were 

found between 3.0mm to 3.2mm. 



Hardness: The hardness of all formulations was 

between 35 – 50 N. 

Friability: Friability of the tablet is not the official 

test but required for the shipment of the product. The 

percentage of friability of the final lab scale 

formulation (F-7) was not more than 0.15% which 

was within the limit (NMT 1%). 

Weight variation: As the weight of the tablet is 

250.0mg the accepted variation is ± 2% and it was 

found that all the successful formulations were 

within the limits. 

In-Vitro Dissolution study: The % CDR after 

15minute was more than 80%. 

Assay: The percentage drug content was found to be 

within 90.0% to 105%. 

Disintegration time: The disintegration time of All 

the formulations were evaluated and results are 

represented in table no 5.7. The disintegration time 

should not be more than 3 minutes for tablets. Based 

on the Precompression and post compression 

parameters F-7 was optimized. After obtaining the 

stability reports, scale up batch was performed with 

bigger batch size 10,000 tablets. 

Stability studies: F–7 were subjected for stability 

studies and was analyzed for physical appearance, 

drug content, dissolution profile and related 

substances. 

Physical appearance: It was found that 

there was no significant change in the color, 

visual appearance in all the tablets during 

 

1 st , 2nd and 3 rd month stability study. 

Disintegration: There was no significant 

difference in DT w.r.t. initial DT. 

Drug content: The drug content in F -8 

showed no significant change w.r.t. to 

initial values. 

Dissolution profile: Dissolution was 

carried out for F – 7 at the intervals 1 st 2 nd 

and 3 rd months and it was found that there 

were no significant changes. 

Hence, the developed dispersible tablet of LNZ of 

formula (F-7) was suitable from pre-compression 

characteristics including dispersion time (DT) and 

also stable over 3- months 

CONCLUSION 

In the present study, an attempt was made to 

formulate a FDC tablet having three ARV drugs. The 

ARV drugs were Nevirapine an NNRTI, Lamivudine 

an NRTI and Zidovudine an NRTI. From the study 

carried out, following conclusions were made as 

given below: 

‣ FT-IR studies revealed that there is no 

chemical interaction between LNZ and the 

excipients used in the study. 

‣ The tablets prepared were found to be good 

without any chipping, capping and sticking 

‣ Formulated tablets gives satisfactorily result 

for various physico-chemical evaluations of 

tablets like tablet dimension, hardness, 

friability, weight variation, in vitro 

dispersion time, wetting time and drug 

content. 

‣ Based on in vitro dispersion time, 

formulation F 7 were found to be promising 

and displayed a dispersion time of 

approximately 55-60 s. 

‣ Initial Analysis using Simultaneous 

estimation by HPLC method was possible 

to show promising assay results. 

‣ In vitro release profile of the dispersible 

tablets were satisfactory and complete drug 

release was achieved within 30 minutes. 

‣ The drug release profile compared with 

individual drug liquid oral suspension form 

of available marketed products. So it’s same 

as marketed product. 

‣ The dosage form was optimized with 

respect to formulation and processing 

parameters, which indicated that 

formulation F-7, was having the desired 

optimum characteristics for taking up 

stability studies. 

‣ Stability studies were carried out as per ICH 

guidelines. After 3 months of accelerated 

stability studies, it was found that the F-7 

was sufficiently stable. 

‣ After successfully optimizing the 

formulation, scale up batch was taken by 

increasing the batch size. 

Table: 1 - Compositions for compatibility study 

Sl.No Combination Composition code 

01 Lamivudine+ Nevirapine+ Zidovudine A 

02 Lamivudine+ Nevirapine+ Zidovudine + lactose monohydrate + MCC+ B 

SSG+ Povidone + Colloidal silicon di oxide+ Mg-st+ Strawberry flavor 

03 Lamivudine+Nevirapine+ Zidovudine+Lactose monohydrate C 

04 Lamivudine+ Nevirapine+ Zidovudine+MCC D 

05 Lamivudine+nevirapine+zidovudine+SSG E 



Table-2: Formulation of F-1 

Sl/no Ingredients Qty/unit(mg) 

1 Lamivudine 30 

2 Nevirapine 50 

3 Zidovudine 60 

4 MCC-200 62 

5 CCS 12 

6 Sucralose 2 

7 Purified talc 2 

8 Magnesium stearate 2 

Table: 3- Formulation of F- 2 





4 MCC-200 62 

5 CCS 12 

6 Sucralose 2 


8 Colloidal silicon dioxide 2 


Table: 4 Formulation of F- 3 (1-5 intragranular and 6-11 extra granular) 

Sl/no Ingredients Qty/unit (mg) 




4 Cross Povidone 6 

5 MCC 40 

6 Sucralose 3 

7 MCC-200 19 

8 Cross Povidone 6 

9 Colloidal silicone dioxide 2 



Table: 5- Formulation of F- 4 (1-5 intragranular and 6-11 extra granular) 





4 MCC(101) 40 

5 Purified water Q S 

6 Sucralose 5 

7 MCC 19 

8 Cross-povidone 12 





Table:6 - Formulation of F- 5 (1-5 intragranular and 6-11 extra granular) 





4 MCC 40 

5 CCS 6 

6 Povidone k-30 3 


8 Sucralose 5 


10 CSS 6 

11 MCC-200 14 

12 Strawberry flavour 1 







4 MCC 65 


6 Sucralose 5 

7 Povidone 2.5 

8 MCC-200 19 

9 Polyplasdone XL-10 15 


11 Strawberry flavor 2 







4 Lactose monohydrate 62 

5 MCC 20 

6 SSG 6 

7 Povidone 2.5 


9 Sucralose 4 

10 Colloidal silicone dioxide 3.5 

11 SSG 7 

12 Strawberry flavor 2 




Table-9- Monograph analysis of Lamivudine 

Sl. No Test Results Specification 

1. Description A white solid A white to off white solid. 

2. Solubility Soluble in water Soluble in water. 

3. Identification A by IR 

Complies 

The sample spectrum should 

exhibit maxima only at the same 

wave length as that of the 

Identification B by 

HPLC 

Complies 

standard. 

HPLC-The retention time of the 

major peak in the chromatogram 

of the Assay preparation should 

correspond to that in the 

chromatogram of the standard 

preparation, as obtained in the 

Assay. 

4. Light absorption at 440mm 0.0013 NMT 0.0015 

5. Water content by KF Nil NMT 0.2% 

6. Melting Range 178 0 C 172 0 C-178 0 C 

7. Residue on ignition 0.013%w/w NMT 0.2%w/w 

8. Heavy Metals Less than 20ppm NMT 20ppm 

9. Bulk density 0.64g/ml For information only 

10. Tapped density 0.85g/ml For information only 

11. Particle size by Malvern 

Master sizer. 

d 10 

d 50 

d 90 

7.39µm 

33.30 µm 

128.65 µm 

12. Foreign Matter The sample is free from 

black particles and 

foreign matter 

13. Limit of lamivudine 

Enantiomer 

NMT 90 µm 

NMT 480 µm 

0.03% NMT 0.30% 

14. Assay by HPLC 99.4% 98.0%-102.0% 

15. Chromatographic purity by 

HPLC: Any peak at RRT of 

about 0.4 

0.0251% NMT0.3% 

16. Any peak at RRT of about 

0.9 salicylic acid Any other 

individual impurity total 

impurities 

0.0656% 

Not detected 

0.0661% 

0.173% 

The sample should be free from 

black particles and foreign 

matter. 

NMT 0.2% 

NMT 0.1% 

NMT 0.1% 

NMT 0.6% 

Table-10- Monograph analysis of Nevirapine 

Si.no Test Results Specification limit 

1. Description White crystalline powder White to off–white, odorless to 

nearly odorless crystalline power. 

2. Solution Insoluble in water, slightly 

soluble in Alcohol and in 

Methanol. 

3. Identification A 

Complies 

Practically insoluble in water, 

slightly soluble in Alcohol and in 

Methanol. 

The sample spectrum should exhibit 

maxima only at the same wave 

length as that of the standard. 

4. Identification B HPLC-The retention time of the 

major peak in the chromatogram of 



Complies the Assay preparation should 

correspond to that in the 

chromatogram of the standard 

preparation, as obtained in the 

Assay. 

5. Water content by KF 2.0% Not more than 3.1% to 3.9% 

6. Residue on ignition 0.012% Not more than 0.1% w/w 

7. Heavy metals Less than 0.001%w/w Not more than 0.001%w/w 

8. Organic volatile 

impurities 

1,4 Dioxan 

Chloroform 

Methylene chloride 

Trichloroethylene 

Less than 380 ppm 

Less than 60ppm 

Less than 600ppm 

Not more than 380 ppm 





9. Assay by HPLC 99.5% 98.0% 102.0% 

10. Foreign matter The sample should be free 

from black particles and 

foreign matter 

The sample should be free from 

black particles and foreign matter. 

11. Melting range 245 0 C Between 240 0 C and 250 0 C 

12. Residual solvent 

O-Xylene 

Dimethyl formamide 

Methanol 

Ethyl acetate 









13. Bulk density 0.56g/ml For information only 

14. Tapped density 0.75g/ml For information only 

15. Particle size by 

Malvern Master 

sizer. 

d 90 

16. Chromatographic 

purity by HPLC 

a) Nevirapine 

related 

compound B 

b) Nevirapine 

related 

compound B 

c) Nevirapine 

related 

compound C 

d) any other 

individual 

unspecified impurity 

e) Total impurity 

9 µm Not more than 10µm 

Less than 0.2% 





NMT 0.2% 

NMT 0.2% 

NMT 0.2% 

NMT 0.1% 

NMT 0.6% 

Table-11 Monograph analysis of Zidovudine 

Sl.no. Test Result Specification 

1. Description White powder White to yellowish powder or 

brownish powder. 

2. Solubility Sparingly soluble in water 

soluble in ethanol. 

Sparingly soluble in water. 

Soluble in ethanol. 



3. Identification by IR The IR absorption spectrum of 

sample preparation exhibit 

maxima only at the same 

wavelengths as that of the 

standard preparation. 

Identification B by 

HPLC 

Complies 

The IR absorption spectrum of 

sample preparation should 

exhibit maxima only at the 

same wavelengths as that of the 

standard preparation. 

HPLC-The retention time of the 

major peak in the 

chromatogram of the Assay 

preparation should correspond 

to that in the chromatogram of 

the standard preparation, as 

obtained in the Assay. 

4. Melting Range 124 0 C 121 0 C – 127 0 C 

5. Specific rotation at 25 0 C 

62.7 0 C +60.5 0 - +63.0 0 

6. Water by KF 0.17% NMT 1.0%w/w 

7. Loss on drying 0.36% NMT 1.0%w/w 

8. Residue on ignition 0.031% NMT 0.25% w/w 

9. Heavy Metals Less than 20ppm NMT 20ppm 

10. Particle size 

d 10 

d 50 

d 90 

3.12µm 

9.55µm 

31.39µm 

11. Foreign matter The sample is free from black 

particles and foreign matter 

NMT 25µm 

NMT 50µm 

NMT 150µm 

The sample should be from 

black particles and foreign 

matter. 

12. Bulk density 0.46 g/ml For information only. 

13. Tapped density 0.65 g/ml For information only. 

14. Assay by HPLC 100.0% 97.0% - 102.0% 

15. Chromatographic purity 

A)By TLC (before spray) 

a)Any individual impurity 

b)sum of the impurities by 

TLC(After spray) 

a)Any individual impurity 

b)Triphenylmethanol 

c)sum of the impurities 

B)by HPLC 

a)zidovudine related 

compound A (stavudine) 

b) zidovudine related 

compound B 

c) zidovudine related 

compound C 

d) Thymidine 

e) any individual 

unknown impurity 

Total impurities 

Total impurities by TLC 

and HPLC 



Less than0 .5% 

ND 

Less than0.5% 

Not detected 

Not detected 

Not detected 

Not detected 

0.006% 

0.016% 

0.516% 

NMT 0.5% 

NMT 3.0% 

NMT 0.5% 

NMT 0.5% 

NMT 3.0% 

NMT 0.2% 

NMT 1.0% 

NMT 2.0% 

NMT .15% 

NMT 0.1% 

NMT 3.0% 


Init 

ial 

1. I 

n 

i 

t 

i 

a 

l 


Figure: 1- IR spectrum of Lamivudine 

Figure: 2- IR spectrum of Nevirapine 

Figure: 3- IR spectrum of Zidovudine 

Test→ 

Period 

↓ 

Table 12: compatibility study result at40 0 C ± 2 0 C /75% ± 5% RH 

IMPURITIES IN PERCENTAGE 

Thymine Cytosine Carboxyli 

c acid 

stavudine 

Specified 

impunity-1 

Specified 

impunity-2 

Unknown 

total 

Total 

A 0.05 0.02 0.16 0.13 0.28 0.37 0.74 1.75 


4 th week 


B 0.05 0.03 0.16 0.14 0.29 0.38 0.76 1.81 

C 0.04 0.02 0.15 0.13 0.30 0.36 0.79 1.78 

D 0.06 0.02 0.16 0.14 0.27 0.35 0.75 1.75 

E 0.05 0.03 0.15 0.14 0.29 0.38 0.78 1.82 

A 0.06 0.02 0.18 0.12 0.30 0.30 0.78 1.93 

B 0.07 0.03 0.18 0.13 0.31 0.28 0.80 1.97 

C 0.08 0.02 0.18 0.14 0.33 0.29 0.79 1.99 

D 0.06 0.04 0.19 0.13 0.32 0.30 0.80 2.01 

E 0.08 0.03 0.18 0.12 0.35 0.29 0.77 2.02 

CODE 

A 

B 

C 

D 

E 

Key for table 5.4 

EXPANSION 

Lamivudine+ Nevirapine+ Zidovudine 

Lamivudine+ Nevirapine+ Zidovudine + lactose monohydrate + MCC+ SSG+ 

Povidone + Colloidal silicon di oxide+ Mg-st+ Strawberry flavor 

Lamivudine+Nevirapine+ Zidovudine+Lactose monohydrate 

Lamivudine+ Nevirapine+ Zidovudine+MCC 

Lamivudine+nevirapine+zidovudine+SSG 

Table: 13: Pre compression parameters 

Formulations Bulk density in gm/ml Tapped density in Carr’s index in % 

gm/ml 

F-1 NP NP NP 

F-2 0.5515 0.689 26.56 

F-3 0.576 0. 735 27.6 

F-4 0.5614 0.725 22.56 

F-5 0.4200 0.572 26.3 

F-6 0.4541 0.5802 21.75 

F-7 05520 0.6675 17.14 

Table: 14: Post compression parameters 

Formulations 

Hardness in 

Newton 

Thickness 

in mm 

Weight 

in mg 

F-1 40-50 2.8-2.9 220-225 

F-2 30-35 2.2-2.6 220-225 

F-3 40-50 3.0-3.2 220-230 

F-4 35-42 3.1-3.2 220-230 

F-5 40-50 3.2-3.3 250-255 

F-6 44-50 3.2-3.3 250-260 

F-7 35-50 3.1-3.2 250-255 



Table: 15: Friability, disintegration and Assay 

Formulations Friability Disintegration 

Assay in % 

In % (seconds) Lamivudine Nevirapine Zidovudine 

F-1 Failed 25-28 102.1 91.7 92.5 

F-2 0.5 25-30 NP NP NP 

F-3 0.2 40-50 103.1 92.7 98.6 

F-4 0.18 30-35 99.8 92.9 101 

F-5 0.17 45-50 102.3 93.8 99.8 

F-6 Nil 15-20 105.1 96.8 100.8 

F-7 0.15 55-60 102.2 99.9 102.5 

Table: 16: Dissolution data 

Formula-tions 5 mins 10 mins 15 mins 30 mins 

Lami Nevi Zido Lami Nevi Zido Lami Nevi Zido Lami Nevi Zido 

F-1 42.1 20.2 43.8 74.9 42.8 73.3 92.5 60.5 91.5 102.1 91.7 92.5 

F-2 NP NP NP NP NP NP NP NP NP NP NP NP 

F-3 50.5 30.5 55.8 77.5 60.6 74.9 98.9 91.3 95.7 103.1 92.7 98.6 

F-4 91.3 80.5 92.3 92.2 81.2 93.9 96.8 90.8 98.7 99.8 92.9 101 

F-5 90.8 82.7 92.9 91.7 83.5 98.7 98.5 91.8 98.9 102.3 93.8 99.8 

F-6 93.8 84.5 93.0 94.5 85.8 100.1 100.5 94.8 98.8 105.1 96.8 100.8 

F-7 94.5 87.9 91.9 96.8 89.8 101.2 100.8 97.6 101.5 102.2 99.9 102.5 

Zidovudine) Lami‏)٭ is Lamivudine, nevi is Nevirapine and Zido is 

Note: NP: Not performed 

Figure: 3 Comparison of dissolution profile of LNZ of F-7. 

120 

%c dr of L ami 

% 

C 

D 

R 

100 

80 

60 

40 

20 

0 

0 10 20 30 40 

TIME IN MIN 

Figure: 4 Dissolution profile of Lamivudine from F-7 



120 

%c dr NVP 

100 

% 

C 

D 

R 

80 

60 

40 

20 

0 

0 10 20 30 40 

T IME IN MIN 

Figure: 5- Dissolution profile of Nevirapine from F-7. 

%c dr Zido 

120 

% 

C 

D 

R 

100 

80 

60 

40 

20 

0 

0 10 20 30 40 

T IME IN MIN 

Figure: 6- Dissolution profile of Zidovudine from F-7 

Table-17. Stability data of optimized formulation for F-7 

Duration →Test↓ First month Second month Third month 

Stability condition 40ºC ±2ºC / 

75% RH 

40ºC ±2ºC / 

75% RH 

40ºC ±2ºC / 

75% RH 

description 

White coloured round, circular 

tablet plain on both sides 

White coloured 

round, circular 

tablet plain on both 

sides 

White coloured round, 

circular tablet plain on 

both sides 

DT limit 

45 sec 50 sec 45 sec 

NMT 3min 

Water content 4.92% 4.24% 4.34% 

Dissolution 

Lamivudine 95.4-98.7% 96.9-100.1% 96.7-101.8% 

Limit: NLT 75%(Q) of Nevirapine 90.1-93.3% 93.8-96.1% 90.9-97.1% 

labeled amt of drug should 

dissolve in 30 min Zidovudine 93.9-96.5% 95.9-99.1% 94.4-100.3% 

Assay 

Each tablet contains 

(90-105% of labeled claim ) 

Lamivudine 100.6% 99.9% 102.4% 

Nevirapine 96.4% 97.5% 99.1% 

Zidovudine 96.5% 96.1% 100.0% 



Fig-7. HPLC for standard graph of LNZ 

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INTERNATIONAL CONGRESS IN PHARMACY AND HEALTH SCIENCES 

Pharma Science Tech Association, Foundation No: AP/PSTA/56/2012. 

Please visit for Details: www.icphsmembership.com 

Totally three types 

FICPHS (Fellowship in International Congress in Pharmacy and Health Sciences), MICPHS (Member in International Congress in 

Pharmacy and Health Sciences), AMICPHS (Associate Member in International Congress in Pharmacy And Health Sciences) 

Eligibility 

FICPHS: Ph.D in Chemistry/ Pharmacy / M.Sc / M.Pharm with 2 years experience, MICPHS: M.Sc / M.Pharm (or) B.Sc / B.Pharm with 

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