Formulation and in vitro release study on poly ( dl-lactide) microspheres containing hydrophilic compounds: glycine homopeptides

Abstract

Poly dl-lactide ( dl-PLA) microspheres containing glycine and its homopeptides viz. diglycine, triglycine, tetraglycine and pentaglycine were prepared using an oil emulsion and solvent evaporation technique. Optimization of processing parameters was studied on glycine and pentaglycine microspheres and it was found that a dl-PLA concentration of 10.3% w/w and an emulsifier (sorbitan sesquioleate) concentration of 0.3% v/v produced yields of microspheres with excellent entrapment when processed under following conditions: emulsions time, 1 min; solvent evaporation time, 2 min; internal phase: external phase ratio, 1:7; stirring speed, 1100 rpm; emulsion temperature, 5°C; and maximumm processing temperature, 35°C. Microspheres prepared as above at four different loadings (2.5, 5.0, 7.5 and 10.0% w/w) were analysed for percent entrapment, in vitro release and morphological characteristics. Gel permeation chromatography established that there was no observable polymer degradation during the 10-day release period with or without the model drug at 37.0 ± 0.5°C. Analysis if glycine or pentaglycine release data using dissolution or diffusion kinetics and scanning electron photographs of the intact and leached microspheres suggested that the release of glycine and its homopeptides from dl-PLA microspheres was mostly by diffusion through the matrix. However, for compounds having low aqueous solubility, e.g., tetra- and pentaglycine, dissolutionm played a rate-limiting role.