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JAC Advance Access originally published online on March 13, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 931-938
© 2003 The British Society for Antimicrobial Chemotherapy

Alginate-based oral drug delivery system for tuberculosis: pharmacokinetics and therapeutic effects

Qurrat-ul-Ain1, Sadhna Sharma1, G. K. Khuller1,* and S. K. Garg2

Departments of 1 Biochemistry and 2 Pharmacology, Postgraduate Institute of Medical Education & Research, Chandigarh 160 012, India

Received 20 August 2002; returned 27 October 2002; revised 17 December 2002; accepted 20 January 2003

Alginate microparticles were developed as oral sustained delivery carriers for antitubercular drugs in order to improve patient compliance. In the present study, pharmacokinetics and therapeutic effects of alginate microparticle encapsulated antitubercular drugs, i.e. isoniazid, rifampicin and pyrazinamide were examined in guinea pigs. Alginate microparticles containing antitubercular drugs were evaluated for in vitro and in vivo release profiles. These microparticles exhibited sustained release of isoniazid, rifampicin and pyrazinamide for 3–5 days in plasma and up to 9 days in organs. Peak plasma concentration (Cmax), Tmax, elimination half-life (t1/2e) and AUC0–{infty} of alginate drugs were significantly higher than those of free drugs. The encapsulation of drug in alginate microparticles resulted in up to a nine-fold increase in relative bioavailability compared with free drugs. Chemotherapeutic efficacy of alginate drug microspheres against experimental tuberculosis showed no detectable cfu values at 1:100 and 1:1000 dilutions of spleen and lung homogenates. Histopathological studies further substantiated these observations, thus suggesting that application of alginate-encapsulated drugs could be useful in the effective treatment of tuberculosis.

Keywords: tuberculosis, pharmacokinetics, alginate, drug delivery, antitubercular drugs

* Corresponding author. Tel: +91-172-747-585, ext. 5174; Fax: +91-172-744-401; E-mail: gkkhuller{at}yahoo.co.nic.in


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