PHARMACOKINETIC STUDY OF MICROSPHERES CONTAINING CHLOROQUINE PHOSPHATE AFTER INTRAMUSCULAR ADMINISTRATION INTO ALBINO RATSV.A. PATEL, R.S.R. MURTHY AND H.V. PATEL
Chloroquine (CQ) is still a drug of choice in the treatment of acute malarial attack. It is inexpensive and widely available, well tolerated under controlled dose. In cases of uncomplicated malaria CQ is usually administered orally, but it may not be feasible in cases of severe or complicated malaria where, parenteral therapy is advocated. However, fast parenteral administration of CQ may cause life threatening toxicity which may limit its clinical use. Encapsulation of Chloroquine in liposomes has proven to reduce toxicity, to improve therapeutic efficacy against malarial parasites and act as a local depot and provide prolonged release in mice. Microspheres of Chloroquine phosphate (CQP) were prepared using cross linked chitosan and were investigated for the in-vitro release profile and in-vivo drug release following intramuscular injection. (i.m.) Different batches of chitosan coated CQP microspheres were prepared and evaluated for their physical properties. The in-vitro study should be reproducible and mimic the in-vivo behavior. So the in-vitro profile can be useful for forecasting its in-vivo effect, but one cannot confirm the performance without in-vivo investigation. Optimized microspheres formulation and free drug were studied for their in-vivo behaviour, pharmacokinetics & biodistribution in albino rats. CQP levels in blood, heart, lung, liver, heart, kidney and spleen as function of time were determined after i.m. injection of free drug and formulation. Intramuscular injection of microspheres showed a highest blood peak level was 8.8 pg/m1 in comparison of free drug which was 18.3 pg/ml. Microspheres formulation showed low Cma higher Vd, longer Ka and greater MRT which could reduce peak blood concentration over longer interval of time and thus reduce drug related toxicity. CQP concentration in heart was low in case of microspheres formulation which is favorable regarding cardio toxicity of the drug. Due to this microsphere formulation is favorable for its therapeutic application.
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