Abstract

Microspheres of chloroquine phosphate (CP) were prepared using cross-linked gelatin and were investigated for the in vitro release profile and in vivo drug release following subcutaneous injection. A series of batches of microspheres were prepared by cold congealing method to optimize parameters like the media of encapsulation (mixture of heavy and light mineral oil in the ratio of 1:3), stirring rate (250 rpm) and pH of the media (4.5) to obtain discrete microsphere in the size range of 50 to 100 mm. The study indicated the significance of the parameters like gelatin to drug ratio and the percentage of formaldehyde (crosslinking agent) to obtain microspheres with high drug entrapment and optimum drug release behaviour. Multiple regression analysis of the values of the cumulative percent drug released in 8 d for ten batches prepared by varying the above two parameters yielded a polynomial equation. This equation was used to calculate the optimum values of gelatin to drug ratio (2.0) and percentage of the formaldehyde (3.99%) for preparing microspheres with ideal drug release behaviour. Subcutaneous injection of microspheres as concentrated suspension in HPMC base in Wistar rats showed blood level concentration between 5.98 and 18.46 μg/ml for a period of 8 days in comparison to 34.8 μg/ml for 6 h following subcutaneous injection of CP solution. Mean residence time of the drug in the body calculated as the ratio of the area of the first moment curve to the area under the concentration vs time curve was 71.4 h for microspheres as against 2.4 h for the drug solution.