Hawkins Valliant Maulding

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.

Prolonged delivery of peptides by microcapsules

Abstract Biodegradable microcapsules may be utilized by injection to deliver drugs over a period of several weeks or more. These systems are especially applicable to highly potent drugs, such as certain peptides and steroids . Peptide-containing microcapsules are frequently fabricated by an organic phase separation technique. This consists of in situ precipitation of the polymeric component and the peptide from a solution of the polymer in a suitable solvent. The resultant microspheres may be injected intramuscular or subcutaneously following processing and suspension in a suitable aqueous vehicle . The polymers most frequently employed are the polyesters. Various molar ratios of lactide:glycolide in the form of poly ( d,l - lactide-coglycolide) have been found useful as matrices for peptides and steroids. Poly ( d,l - lactide-co-glycolide) has elicited negligible toxicity or inflammatory response in studies carried out to date. The irritancy of these materials is comparable to an IM dose of saline . These delivery systems are relatively complex. Interactions between drugs and polymeric components may occur. Amines have been noted to accelerate the hydrolysis of polyesters. It has been found that the degradation of some peptides is exacerbated in the presence of polyesters . Drug release of water-soluble compounds, such as peptides occurs in a biphasic manner. There is an initial drug burst in the first day or two, followed by a minimum. A second release phase begins as the polymeric matrix starts to degrade. Plasma levels attainable are in the ng/ml range levels in animals and, in certain cases, efficacy has been maintained for one to two months .

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.