Accelerated Polymer Biodegradation of Risperidone Poly(d, l-Lactide-Co-Glycolide) Microspheres

Abstract

Abstract. The influence of a tertiary amine, namely risperidone (pKa07.9) 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 drugloaded 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.

A reproducible accelerated in vitro release testing method for PLGA microspheres

“…However, the molecular weight of these microspheres exponentially decreased in the presence of risperidone (Fig. 1B), indicating much faster polymer degradation, which was consistent with previous literature reports Selmin et al, 2012).…”

“…Risperidone, a tertiary amine drug with a pKa of 8.18 (20°C), has been shown to catalyze PLGA hydrolysis and degradation, thus resulting in a dramatic decrease in polymer molecular weight (Fig. 1) Selmin et al, 2012). Since the prepared risperidone microspheres were similar in composition, critical physicochemical properties of the microspheres may be mainly responsible for the different rates of microsphere degradation and drug diffusion and thereby the different in vitro release characteristics were observed.…”

Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue Regeneration Applications

“…For instance, the basic nature of drugs can increase PLGA-based DDSs degradation due to their hydrolytic capability, leading to the breakage of ester bonds in the copolymer chain. [143] Beyond the acid-basic behavior of drugs, their solubility and molecular weight are also important factors affecting drug release. [34,144] According to the composition of PLGA, the hydrophilic/hydrophobic ratio of the polymer is variable and may lead to different solubility values and, consequently, to different release profiles.…”

Development and Validation of RP-UPLC Method for Determination of Related Substances in Risperdal® Consta®

“…Bindu et al have reported a UPLC method for quantitating six impurities of paliperidone (9-hydroxy resperidone) in 8 min [7]. Nejedly et al developed a UHPLC method for discrimination the main degradation impurities from risperidone tablet [8]. The new UHPLC method has reduced 4 times of total analysis time comparing with original pharmacopoeial HPLC method.…”