Introduction: 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. Methods and Materials: Risperidone and blank microspheres were fabricated at two lactide/glycolide ratios, 65:35 and 85:15. The microspheres were characterized for drug loading by HPLC, particle size by laser diffractometry and surface morphology by scanning electron microscopy (SEM). Polymer degradation studies were carried out with drug loaded microspheres, blank microspheres and blank microspheres in presence of free risperidone in 0.02M PBS containing 0.02% Tween®80 at 37 °C. Molecular weight was monitored by gel permeation chromatography (GPC). Results and Discussion: Risperidone and blank microspheres had similar size distribution and were spherical with a relatively non-porous 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 intra-batch 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. Conclusion: 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.

Accelerated polymer biodegradation of risperidone poly(d, l-lactide-co-glycolide) microspheres / F. Selmin, P. Blasi, P.P. DeLuca. - In: AAPS PHARMSCITECH. - ISSN 1530-9932. - 13:4(2012 Dec), pp. 1465-1472. [10.1208/s12249-012-9874-4]

Accelerated polymer biodegradation of risperidone poly(d, l-lactide-co-glycolide) microspheres

F. Selmin;
2012-12

Abstract

Introduction: 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. Methods and Materials: Risperidone and blank microspheres were fabricated at two lactide/glycolide ratios, 65:35 and 85:15. The microspheres were characterized for drug loading by HPLC, particle size by laser diffractometry and surface morphology by scanning electron microscopy (SEM). Polymer degradation studies were carried out with drug loaded microspheres, blank microspheres and blank microspheres in presence of free risperidone in 0.02M PBS containing 0.02% Tween®80 at 37 °C. Molecular weight was monitored by gel permeation chromatography (GPC). Results and Discussion: Risperidone and blank microspheres had similar size distribution and were spherical with a relatively non-porous 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 intra-batch 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. Conclusion: 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.
mass loss; microencapsulation; PLGA microspheres; polymer degradation; risperidone; tertiary amine drug
Settore CHIM/09 - Farmaceutico Tecnologico Applicativo
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/215556
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