Parameters affecting in-liquid drying microencapsulation and release rate of cefaclor

An in-liquid drying microencapsulation method for producing sustained release cefaclor (CF) microspheres has been developed. Sieved fractions of CF monohydrate particles together with polyvinylpyrrolidone (M_W ~40 000) were dispersed in a solvent mixture of dichloromethane with cyclohexane (40:60 v/v) containing dissolved ethylcellulose (EC; 48-49.5% ethoxy content). Encapsulation was effected by adding the dispersion to a stirred aqueous medium saturated with CF. The resulting microspheres (collected overnight and oven-dried at 40°C) were examined for size and surface features by scanning electron microscopy, and for solid-state interactions and phase changes using differential scanning calorimetry (DSC), thermogravimetric analysis and powder X-ray diffractometry. The rate and extent of CF release in aqueous medium was measured at 37°C using the USP rotating basket method at 100 rpm. The size, degree of sphericity, and rate of CF release of the microspheres were all shown to depend on the CF to EC mass ratio and the stirring speed employed in encapsulation. Higher EC to CF mass ratio and lower stirring speed afforded microspheres with slower release rate of CF. The rate of CF release from the microspheres fit the simplified Higuchi's planar model equation, and for the samples prepared at various EC:CF ratios, exhibited a strong correlation with drug loading (r=0.98; n=4 (mean values); p<0.05). DSC studies on the samples indicated an absence of molecular interactions between EC and CF in the microspheres. The results demonstrate that the in-liquid drying method, if appropriately optimized, could be used to produce sustained-release CF microspheres with the desired release pattern and physical properties. Copyright (C) 1998 Elsevier Science B.V.