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AAPS PharmSciTech. 2006 March; 7(1): E1–E9.
Published online 2006 January 3. doi:  10.1208/pt070101
PMCID: PMC2750708

Formulation and in vitro, in vivo evaluation of extended- release matrix tablet of Zidovudine: Influence of combination of hydrophilic and hydrophobic matrix formers


The aim of the present study was to prepare and characterize extended-release matrix tablets of zidovudine using hydrophilic Eudragit RLPO and RSPO alone or their combination with hydrophobic ethyl cellulose. Release kinetics was evaluated by using United States Pharmacopeia (USP)-22 type I dissolution apparatus. Scanning electron microscopy was used to visualize the effect of dissolution medium on matrix tablet surface. Furthermore, the in vitro and in vivo newly formulated sustained-release zidovudine tablets were compared with conventional marketed tablet (Zidovir, Cipla Ltd, Mumbai, India). The in-vitro drug release study revealed that either Eudragit preparation was able to sustain the drug release only for 6 hours (94.3%±4.5% release). Combining Eudragit with ethyl cellulose sustained the drug release for 12 hours (88.1%±4.1% release). Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release. In vivo investigation in rabbits showed sustained-release pharmacokinetic profile of zidovudine from the matrix tablets formulated using combination of Eudragits and ethylcellulose. In conclusion, the results suggest that the developed sustained-release tablets of zidovudine could perform therapeutically better than conventional dosage forms, leading to improve efficacy and better patient compliance.

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Selected References

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1. Chien YW, Wearley LL. AIDS and chemotherapy. Drugs Today. 1989;25:19–25.
2. Jain S, Umamaheshwari RB, Bhadra D, Jain NK. Ethosomes: a novel vesicular carrier for enhanced transdermal delivery of an anti-HIV agent. Ind J Pharm Sci. 2004;66:72–81.
3. Jain S, Tiwary AK, Jain NK. Transdermal delivery of an anti-HIV agent using elastic liposomes: mechanism of action., Curr Drug Deliv. In press. [PubMed]
4. Kieburtz KD, Seidllin M, Lambert JS, Dollis R, Reichman R, Valentine T. Extended follow-up of neuropathy in patients with AIDS and AIDS related complex treated with dideoxyinosine. J Acquir Immuno Defic Syndrom. 1992;5:60–64. [PubMed]
5. Klecker RW, Collins JM, Yarchoan R, et al. Plasma and cerebrospinal fluid pharmacokinetics of 3′ azido-3′-deoxythymidine: a novel pyrimidine analog with potential application for the treatment of patients with AIDS and related disease. Clin Pharmacol Ther. 1987;41:407–412. doi: 10.1038/clpt.1987.49. [PubMed] [Cross Ref]
6. Salsa T, Veiga F, Pina ME. Oral controlled-release dosage forms. I. Cellulose ether polymers in hydrophilic matrices. Drug Dev Ind Pharm. 1997;23:929–938. doi: 10.3109/03639049709148697. [Cross Ref]
7. Sanchez-Lafuente C, Furlanetto S, Fernandez-Arevalo M, et al. Didanosine extended release matrix tablets: optimization of formulation variables using statistical experimental design. Int J Pharm. 2002;237:107–118. doi: 10.1016/S0378-5173(02)00028-5. [PubMed] [Cross Ref]
8. Alderman DA. A review of cellulose ethers in hydrophilic matrices for oral controlled-release dosage forms. Int J Pharm Tech Prod Mfr. 1984;5:1–9.
9. Gohel MC, Patel TP, Bariya SH. Studies in preparation and evaluation of pH independent sustained-release matrix tablets of verapamil HCl using directly compressible Eudragits. Pharm Dev Technol. 2003;8:323–333. doi: 10.1081/PDT-120024686. [PubMed] [Cross Ref]
10. Liu J, Zhang F, McGinity JW. Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion. Eur J Pharm Biopharm. 2001;52:181–190. doi: 10.1016/S0939-6411(01)00162-X. [PubMed] [Cross Ref]
11. Bettini R, Colombo P, Massimo G, Catellani PL, Vitali T. Swelling and drug release in hydrogel matrices: polymer viscosity and matrix porosity effects. Eur J Pharm Sci. 1994;2:213–219. doi: 10.1016/0928-0987(94)90025-6. [Cross Ref]
12. Reddy KR, Mutalik S, Reddy S. Once daily sustained release matrix tablets of nicorandil: formulation and in vitro evaluation. AAPS Pharm Sci Tech. 2003;4:E61–E61. doi: 10.1208/pt040461. [PMC free article] [PubMed] [Cross Ref]
13. Aulton ME, Wells TI. Pharmaceutics: The Science of Dosage Form Design. London, UK: Churchill Livingstone; 1988.
14. The Pharmacopoeia of India. Delhi, India: Controller of Publication; 1996.
15. Higuchi T. Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52:1145–1149. doi: 10.1002/jps.2600521210. [PubMed] [Cross Ref]
16. Korsmeyer RW, Gurny R, Docler E, Buri P, Peppas NA. Mechanism of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25–35. doi: 10.1016/0378-5173(83)90064-9. [Cross Ref]
17. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60:110–111. [PubMed]
18. Mockel JE, Lippold BC. Zero order release from hydrocolloid matrices. Pharm Res. 1993;10:1066–1070. doi: 10.1023/A:1018931210396. [PubMed] [Cross Ref]
19. Al-Taani BM, Tashtoush BM. Effect of microenvironment pH of swellable and erodable buffered matrices on the release characteristics of diclofenac sodium. AAPS Pharm Sci Tech. 2003;4:E43–E43. doi: 10.1208/pt040343. [PMC free article] [PubMed] [Cross Ref]
20. Pereira AS, Kenney KB, Cohen MS, et al. Simultaneous determination of lamivudine and zidovudine concentrations in human seminal plasma using high-performance liquid chromatography and tandem mass spectrometry. J Chromatogr B Biomed Sci Appl. 2000;742:173–183. doi: 10.1016/S0378-4347(00)00162-6. [PubMed] [Cross Ref]
21. Ebube NK, Hikal A, Wyandt CM, Beer DC, Miller LG, Jones AB. Sustained release of acetaminophen from heterogeneous matrix tablets, influence of polymer ratio, polymer loading and coactive on drug release. Pharm Dev Technol. 1997;2:161–170. doi: 10.3109/10837459709022621. [PubMed] [Cross Ref]
22. Blum MR, Liao SHT, Good SS, De Miranda P. Pharmacokinetic and bioavailability of zidovudine in human. Am. J Med. 1988;85:189–194. doi: 10.1016/S0002-9343(88)80340-1. [PubMed] [Cross Ref]
23. Richman DD, Fischl MA, Grieco MH, et al. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS related complex. N Engl J Med. 1987;317:192–197. doi: 10.1056/NEJM198707233170402. [PubMed] [Cross Ref]
24. Katikaneni PR, Upadrashia SM, Neau SH, Mitra AK. Ethylcellulose matrix controlled-release tablets of a water soluble drug. Int J Pharm. 1995;123:119–125. doi: 10.1016/0378-5173(95)00060-V. [Cross Ref]
25. Efentakis M, Koutlis A. Release of furosemide from multiple unit and single unit preparations containing different viscosity grades of sodium alginate. Pharm Dev Technol. 2001;6:91–98. doi: 10.1081/PDT-100000048. [PubMed] [Cross Ref]

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