Spray-Dried Lamivudine Microspheres

Ola Mhawed, Manal El-Ashmoony, Tamer Essam, Omaima Elgazayerly

Abstract


The objective of present study was to develop controlled release lamivudine microspheres using spray drying encapsulation technique to increase the efficacy of anti retroviral drug, lamivudine against HIV infections and decrease its gastric unwanted effects. Low and high molecular weight chitosan and hydroxypropyl methylcellulose (HPMC) in different drug-polymer ratios were used for the preparation of microspheres.  A 32 factorial experimental design was employed to explore the effect of polymer type (X1) and drug percentage (X2) on the release rate of the drug from the microspheres. The yield value (Y1), encapsulation efficiency (Y2), particle size (Y3) and the release efficiency percentage (Y4) were selected as the dependent variables. Drug release from microspheres was compared with the release behavior of commercially available formulation Lamidine®. The best encapsulation efficiencies were obtained when chitosan of low molecular weight (CL) or HPMC were used for microencapsulation. Tissue Culture Infective Dose that causes CPE for 50 % of cells (TCID50) was calculated using Reed-Muench formula. TCID50 of the prepared formulae was higher than TCID50 of Control after 5 hours. Marked retardation of lamivudine release from its prepared microspheres indicates the success of controlling drug release over 5 hours.

 


References


Anthony S.F. and Clifford H.L. (2001) Human immunodeficiency virus (HIV) disease: AIDS and related disorders. In: Harrisons Principles of Internal Medicine (eds Braunwald E., Fauci A.S., Kasper D.L., Hauser S.L.,Longo D.L., Jameson J.L.), pp. 1852-1913. McGraw-Hill, New York.

Berthold A., Cremer K., Kreuter J. (1996) Preparation and characterisation of chitosan microspheres in drug carrier for prednisolone sodium phosphate as model for anti-inflammatory drugs. J. Control. Rel. 39, 17-25.

Betty J.D. (2000) Human immunodeficiency virus (HIV)-antiretroviral therapy. In: Textbook of Therapeutics: Drug and Disease Management (eds Herfindal E.T. & Gouley D.R.), pp. 1555-1582. Lippincott Williams & Wilkins, Philadelphia Pa.

Conte U., Giunchedi P., Maggi L., Torre M.L. (1994) Spray dried albumin microspheres containing nicardipine. Eur. J. Pharm. Biopharm. 40, 203-208.

Cuna M., Vila Jato J.L., Torres D. (2000) Controlled-release liquid suspensions based on ion-exchange particles entrapped within acrylic microcapsules. Int. J. Pharm. 2,151–158.

Desai K.G.H., Park H.J. (2005) Encapsulation of vitamin C in tripolyphosphate cross-linked chitosan microspheres by spray drying. J. Microencapsul. 22(2), 179-192.

Desai K.G.H., Park H.J. (2005) Encapsulation of vitamin C in tripolyphosphate cross-linked chitosan microspheres by spray drying. J. Microencapsul. 22 (2), 179-192.

Dubey R.R., Parikh R.H. (2004) Studies of PLGA microspheres. Pharm. Tech. Eur. 16, 23-34.

Filipović-Grčić J., Perissutti B., Moneghini M., Voinovich D., Martinac A., Jalšenjak I. (2003) Spray dried carbamazepine-loaded chitosan and HPMC microspheres: preparation and characterization. J. Pharm. Pharmacol. 55, 921-931.

Gavin E., Hegge A.B., Rassu G., Sanna V., Testa C., Pirisino G., Karlsen J., Giunchedi P. (2006) Nasal administration of carbamazepine using chitosan microspheres, In-vitro/in-vivo studies. Int. J. Pharm. 307, 9-15.

Genta I., Perugini P., Pavanetto F. (1998) Different molecular weight chitosan microspheres: influence on drug loading and drug release. Drug Dev. Ind. Pharm. 24, 779-784.

Giunchedi P., Gavini E., Palmieri G.F., Bonacucina G. (2000) Tableted polylactide microspheres Prepared by a w/o emulsion-spray drying method. J. Microencapsul. 17, 711-720.

Gohel M.C., Parikh R.K., Amin A.F., Surati A.K. (2005) Preparation and formulation optimization of sugar cross-linking gelatin microspheres of declofenac sodium. Indian J. Pharm Sci. 67, 575-581.

He P., Davis S.S., Illum L. (1999) Chitosan microspheres prepared by spray drying. Int. J. Pharm. 187, 53-65.

Higuchi T. (1961) Rate of release of medicaments from ointment bases containing drugs in suspension. J. Pharm. Sci. 50, 874-875.

Himadrisen , Surva Kumar J. (2005) Long acting composition containing zidovudine and lamivudine. US patent publication US 20050175694A1, 11 August 2005.

Illum L., Farraj N.F., Davis S.S. (1994) Chitosan as novel nasal delivery system for peptide drugs. Pharm. Res. 11, 1186-1189.

Khan K.A. (1975) The concept of dissolution efficiency. J. Pharmacol. 27, 98-99.

Lim S.T., Martin G.P., Berry D.J., Brown M.B. (2000) Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaloranic acid and chitosan. J. Control. Rel. 66, 281-292.

Merril D.P., Moonis M., Chou T.C .and Hirsch M.S. (1996) Lamivudine or stavudine in two - and three - drug combinations against human immunodeficiency virus type 1 replication in vitro. J. Infect. Dis. 173, 355-364.

Moretti M.D.L, Gravini E., Juliano C., Pirisino G., Giunchedi P. (2001) Spray dried microspheres containing ketoprofen formulated into capsules and tablets. J. Microencapsul. 18, 111-121.

Moretti M.D.L., Gravini E., Juliano C., Pirisino G., Giunchedi P. (2001) Spray dried microspheres containing ketoprofen formulated into capsules and tablets. J. Microencapsul. 18, 111-121.

Palmieri G.F., Bonacucina G., Martino P., Martelli S. (2001) Spray-drying a method for microparticulate controlled release systems preparation: advantages and limits. I. Water soluble drugs. Drug. Dev. Ind. Pharm. 27, 195-204.

Parakash K., Raju R.N., Shanta K.K., Lakshmi M.N. (2007) Preparation and characterization of lamivudine microcapsules using various cellulose polymers. Tropical J. of Pharm. Res. 6(4), 841-871.

Pavanetto F., Genta I., Giunchedi P., Conti B., Conte U. (1994) Spray dried albumin microspheres for the intra-articular delivery of dexamethasone. J. Microencapsul. 11, 445-454.

Peppas N.A. (1985) Analysis of Fickian and non-Fickian drug release from polymers. Pharm. Acta. Helv. 60, 110.

Ravi P.R., Ganga S., Saha R.N. (2007) Design and study of lamivudine oral controlled release tablets. AAPS Pharm. Sci. Tech. 8(4), 167–175..

Reed L.J., Muench H. (1983) A simple method of estimating fifty percent endpoints. Am. J. Hyg. 27, 493- 497.

Sheu, T-Y. and Rosenberg M. (1998) Microstructure of microcapsules consisting of whey proteins and carbohydrates. J. Food Sci. 63(3), 491-494.

Sweetman S.C. (2007) Martindale: The Complete Drug Reference. Pharmaceutical Press.

Takeuchi H., Handa T., Kawashima Y. (1989) Controlled release thyophylline with acrylic polymers prepared by spray drying technique. Drug. Dev. Ind. Pharm. 15, 1999-2016.

Wagner J.G. (1998) Interpretation of percent dissolved-time plots derived from in vitro testing of conventional tablets and capsules. J. Pharm. Sci. 58, 1253-1257.

Wan L.S.C., Lim L.Y., Soh B.L. (1994) Drug release from chitosan beads. STP Pharm. Sci. 4, 195-2000.

Wang F.J., Wang C.H. (2002) Effects of fabrication conditions on the characteristic of etanidazole spray-dried microspheres. J. of Microencapsul. 19, 495-510.


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