title: Accelerated polymer biodegradation of risperidone poly(D, L-lactide-co-glycolide) microspheres.
abstract: The influence of a tertiary amine, namely risperidone (pKa = 7.9) on the degradation of poly(D, L lactide-co-glycolide) (PLGA) microspheres was elucidated. Risperidone and blank microspheres were fabricated at two lactide/glycolide ratios, 65:35 and 85:15. The microspheres were characterized for drug loading by high-performance liquid chromatography, particle size by laser diffractometry, and surface morphology by scanning electron microscopy. Polymer degradation studies were carried out with drug-loaded microspheres and blank microspheres in presence of free risperidone in 0.02 M PBS containing 0.02% Tween®80 at 37°C. Molecular weight was monitored by gel permeation chromatography. Risperidone and blank microspheres had similar size distribution and were spherical with a relatively nonporous smooth surface. The presence of risperidone within the microspheres enhanced the hydrolytic degradation in both polymeric matrices with faster degradation occurring in 65:35 PLGA. The molecular weight decreased according to pseudo-first-order kinetics for all the formulations. During the degradation study, the surface morphology of drug-loaded microspheres was affected by the presence of risperidone and resulted in shriveled microspheres in which there appeared to be an intrabatch variation with the larger microspheres being less shriveled than the smaller ones. When blank microspheres were incubated in free risperidone solutions, a concentration-dependent effect on the development of surface porosity could be observed. Risperidone accelerates the hydrolytic degradation of PLGA, presumably within the microenvironment of the drug-loaded particles, and this phenomenon must be taken into consideration in designing PLGA dosage forms of tertiary amine drugs.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via G. Colombo, 71-20133, Milan, Italy. francesca.selmin@unimi.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Selmin
authors.forename: Paolo
authors.initials: P
authors.lastname: Blasi
authors.forename: Patrick P
authors.initials: PP
authors.lastname: DeLuca
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006868:Hydrolysis; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry; D018967:Risperidone / Q000737:chemistry*
chemical_list: D011108:Polymers; D011136:Polysorbates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D018967:Risperidone