Pharmacokinetics and biodistribution of zidovudine loaded in a solidified reverse micellar delivery system.

Emmanuel M. Uronnachi, John Dike Ogbonna, Franklin C. Kenechukwu, Mumuni A. Momoh, Anthony A. Attama, Vincent C. Okore


The aim of the research was to study the stability, release profile, pharmacokinetic and biodistribution properties of zidovudine (AZT)-solidified reverse micellar microparticulate. Lipid matrices formulated with Phospholipon® 90H and goat fat at ratios of 1:1, 2:1, 3:1 and 2:3 were used to prepare AZT-loaded SLM by melt dispersion followed by lyophilization. In vitro release studies of the drug were carried out using a sequential drug release method in both SGF (pH 1.2) and SIF (pH 7.2) while the in vivo drug release studies were carried out using Wistar albino rats. The result of our findings showed that the drug is compatibility with the lipid matrix with the 1:1 showing the most stable microparticle preparation which was then optimized. The formulations showed a concentration dependent increase in their concentration maximum (Cmax) with values of 116.05 µg/ml, 124.21 µg/ml, 128.95 µg/ml, 138.95 µg/ml and time to reach maximum concentration (Tmax) values of 5h, 8 h, 8 h, and 5 h for batches B1, B2, B3 and B4 containing 1 %, 2 %, 3 % and 5 % of AZT respectively. The area under curves (AUCs) of the microparticles formulated showed that the bioavailabilities of the microparticles were comparable to that of the conventional release tablet. The biodistribution studies of the microparticles in rats showed highest concentration of the drug in the liver with the least in the brain and higher biodistribution in various organs than pure AZT. The data suggested that SLM could be a promising drug delivery system to improve on the shortcomings of pharmacokinetics and bio-distribution properties of conventional AZT tablets like fluctuation in blood levels of the drug.


solidified lipid microparticle (SLM), lipid matrix, Phospholipon® 90H, human immunodeficiency virus, highly active antiretroviral therapy

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Büchen-Osmond C, editor. ICTVdB management lentivirus. ICTVdB - The universal virus database. Vol. 4. Columbia University; New York, USA: 2006.

Büchen-Osmonda C, editor. ICTVdB management spumaretrovirinae. ICTVdB - The universal virus database. Columbia University; New York, USA: 2006.

Lawn SD. AIDS in Africa: the impact of coinfections on the pathogenesis of HIV-1 infection. J. Infect. Dis. 2004; 48: 1–12.

Reeves JD, Doms RW. Human immunodeficiency virus type 2. J. Gen. Virol. 2002; 83: 1253–1265.

Joint United Nations Programme on HIV/AIDS and World Health Organization. AIDS epidemic update. Geneva: 2005.

UNAIDS. AIDS epidemic update. Geneva: 2007.

Connor, E. M., R. S. Sperling, R. Gelber, P. Kiselev, G. Scott, M. J. O'Sullivan, R. VanDyke, M. Bey, W. Shearer, R. L. Jacobson, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N. Engl. J. Med.1994; 331: 1173-1180.

Vanhove GF, Kastrissios H, Gries JM. Verotta D, Park K, Collier AC, Squires K, Sheiner LB, Blaschke TF. Pharmacokinetics of saquinavir, zidovudine, and zalcitabine in combination therapy. Antimicrobial Agents and Chemotherapy.1997; 41: 2428–2432.

De Clercq E. "HIV resistance to reverse transcriptase inhibitors." Biochem Pharmacol. 1994; 47 (2): 155–169.

Yarchoan R, Mitsuya H, Broder S. AIDS therapies. Sci. Am. 1988; 259 (4): 110–119.

Peralta G, Sánchez MB, Echevarría S, Valdizán EM, Armijo JA. Pglycoprotein and human immunodeficiency virus infection, Enferm Infecc Microbiol Clin 2008; 26: 150‐159.

Rossi JJ, Elkins D, Zaia JA, Sullivan S. Ribozymes as anti‐HIV‐1 therapeutic agents: principles, applications, and problems. AIDS Res Hum Retroviruses 1992; 8:183‐189.

Robins T, Plattner J. HIV protease inhibitors: their anti‐HIV activity and potential role in treatment. J Acquired Immune Defic Syndr 1993; 6:162‐170.

Costa K. Recent advances in novel drug delivery systems. Azjono J. Nanotechnol Online. 2006; 2: 1-11.

Westesen K, Siekmann B. Solid lipid nanoparticles of bioactive agent and method for the the manufacture and use thereof. United States Patent. 5785 976. 1998.

Hu FQ, Yuan H, Zhang HH, Fang M. Preparation of solid lipid nanoparticles with clobetasol propionate by a novel solvent diffusion method in aqueous system and physicochemical characterization. Int. J. Pharm. 2002; 239: 121-128.

Lippacher A, Muller RH, Mader K. Preparation of semisolid drug carriers for topical application based on solid lipid nanoparticles. Int. J. Pharm. 2001; 214: 9-12.

Reithmier H, Hermann J, Gopferich A. Lipid microparticles as a parenteral controlled release device for peptides. J. Control Rel., 2001; 73: 339–350.

Milak S, Medicott N, Tucker IG. Solid lipid micro particles containing loratadine prepared using a micro mixer. J. Microencapsul. 2006; 23: 823–831.

Jaspart S, Bertholet P, Piel G, Dogne JM, Delattre L, Evrad B. Solid lipid microparticles as sustained release system for pulmonary drug delivery. Eur. J. Pharm. Biopharm. 2007; 65: 47–56.

Attama AA, Nkemnele MO. In vitro evaluation of drug release from self-emulsifying drug delivery systems using a biodegradable homolipid from Capra hircus. Int. J. Pharm. 2005; 304: 4-10.

Friedrich I, Müller-Goymann CC. Characterization of solidified reverse micellar solutions and production development of SRMS-based nanosuspensions. Eur. J. Pharm. Biopharm. 2003; 56(1): 111-119.

European Community Council Directive on the ethics of experiments involving laboratory animals (86/609/EEC), November 24, 1986.

Reddy LH, Murthy RSR. Etoposide-loaded nanoparticles made from glyceride lipids: formulation, characterization, in vitro drug release, and stability evaluation. AAPS PharmSciTech 2005;6 Article 24.

Galinsky ER, and Svenson CK. Basic pharmacokinetics. In Remington: The science and practice of pharmacy, 19th ed. Easton P.A, Mack Publishing, 1995; vol II. pp.1127-1144.

Pachuau L, Sarkar S, Mazumdar B. Formulation and evaluation of matrix microspheres for simultaneous delivery of salbutamol sulphate and theophylline. Tropical J. Pharm Res. 2008; 7(2): 995-1002.

Higuchi T. Mechanism of sustained action medication. Theoretical analysis of rate of solid drugs dispersed in solid matrices. J. Pharm. Sci. 1963; 52: 1145–1149.

Umeyor EC, Kenechukwu FC, Ogbonna JD, Chime SA, Attama AA. Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo. J Microencapsul. 2012, 1–12.DOI: 10.3109/02652048.2011.651495.

Yonamine CM, Costa H, Silva JAA, Muramoto E, Rogero JR, Troncone LRP, Camillo, MAD. Biodistribution studies of bee venom and spider toxin using radiotracers. J. Venom. Anim. Toxins incl. Trop. Dis.2005; 11(1): 39-50.

Gibaldi M. Compartmental and noncompartmental pharmacokinetics. In: Gibaldi M. Ed. Biopharmaceutical and clinical pharmacokinetics. Philadelphia: PA. Lea & Febiger. 1991. pp.1-16.

Blum MR, Liao SHT, Good SS, De Miranda P. Pharmacokinetic and bioavailability of zidovudine in human. Am. J. Med. 1988; 85: 189-194.

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.

Kuksal A, Tiwary AK, Jain NK, Jain S. Formulation and in vitro, in vivo evaluation of extended- release matrix tablet of zidovudine: Influence of combination of hydrophilic and hydrophobic matrix formers. AAPS PharmSciTech. 2006; 7(1): Article 1. DOI: 10.1208/pt070101.

Uronnachi EM, Ogbonna JDN, Kenechukwu FC, Attama AA, Chime SA. Properties of zidovudine loaded solidified reverse micellar microparticles prepared by melt dispersion. Journal of Pharmacy Research.2012; 5(5): 2870-2874.


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