Jane Edna Pearson

Biodegradable microcapsules: Acceleration of polymeric excipient hydrolytic rate by incorporation of a basic medicament

The degradation rate of the polymer, poly(d,l-lactide), was accelerated in the presence of the tertiary amino compound, thioridazine. The poly(d,l-lactide) component of micro-capsules containing up to 50% thioridazine free base showed a decrease in molecular weight during microcapsule fabrication and in the course of dissolution-rate studies. This effect was evidenced on dissolution by an unexpectedly rapid release of thioridazine as a function of time. Polymer hydrolysis was neither appreciable in microcapsules containing no drug nor when the amino group of thioridazine was protonated in the form of the pamoate salt. This enhancement of degradation rate may be attributed to amine-influenced hydrolysis of poly(d,l-lactide). Thioridazine blood levels obtained from the microcapsules in dogs paralleled the in vitro results. There was an initial lag time followed by a rapid release of the drug producing blood levels over about a six-day span. Polymeric decomposition was also determined in vitro, pH 7.4, by gel-permeation chromatography. The results indicate a rapid molecular-weight decrease of the polymer, corroborating the in vivo and in vitro results.

Evaluation of biodegradable microspheres prepared by a solvent evaporation process using sodium oleate as emulsifier

Abstract Biodegradable microspheres were prepared by a solvent evaporation (emulsion) process using sodium oleate as the emulsifier. Drugs with aqueous solubility of about 0.02 mg/ml or less were successfully microencapsulated to give reproducible, controlled release. Drug release was found to be affected by drug loading, polymer molecular weight, polymer composition and polymer concentration in the organic phase of the emulsion.