PURPOSE: Nonadherence to antipsychotic medications is a major obstacle preventing optimal outcomes for patients with schizophrenia. Extended release systems exist in the form of depot injections, but these formulations exhibit several disadvantages. To address these concerns, we previously demonstrated proof of concept for an antipsychotic implant containing risperidone and the biodegradable polymer poly(lactic-co-glycolic) acid (PLGA). METHODS: We build upon recently published data by utilizing a scalable single-screw extrusion system for the production of PLGA-risperidone implants. Implants were composed of 40% risperidone and 60% PLGA, with varying ratios of lactide to glycolide (50:50, 65:35, 75:25 or 85:15). Risperidone release was assessed in vitro and in vivo in rats, and Level A, B and C correlations (IVIVCs) attempted for all. Bioavailability was verified with locomotor testing RESULTS: Level B analysis yielded the greatest correlation between in vitro and in vivo data (R (2) = 0.9425), while Level C yielded the lowest (R (2) = 0.8336). Although, based on qualitative results, a Level A correlation was not achieved, it did produce an R (2) of 0.9261. Locomotor testing demonstrated that peak serum concentrations coincide with significant reductions in activity. CONCLUSION: Data demonstrate the applicability of our modeling system and advance long-term, implantable antipsychotics toward clinical application.
PURPOSE: Nonadherence to antipsychotic medications is a major obstacle preventing optimal outcomes for patients with schizophrenia. Extended release systems exist in the form of depot injections, but these formulations exhibit several disadvantages. To address these concerns, we previously demonstrated proof of concept for an antipsychotic implant containing risperidone and the biodegradable polymer poly(lactic-co-glycolic) acid (PLGA). METHODS: We build upon recently published data by utilizing a scalable single-screw extrusion system for the production of PLGA-risperidone implants. Implants were composed of 40% risperidone and 60% PLGA, with varying ratios of lactide to glycolide (50:50, 65:35, 75:25 or 85:15). Risperidone release was assessed in vitro and in vivo in rats, and Level A, B and C correlations (IVIVCs) attempted for all. Bioavailability was verified with locomotor testing RESULTS: Level B analysis yielded the greatest correlation between in vitro and in vivo data (R (2) = 0.9425), while Level C yielded the lowest (R (2) = 0.8336). Although, based on qualitative results, a Level A correlation was not achieved, it did produce an R (2) of 0.9261. Locomotor testing demonstrated that peak serum concentrations coincide with significant reductions in activity. CONCLUSION: Data demonstrate the applicability of our modeling system and advance long-term, implantable antipsychotics toward clinical application.
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Authors: P A Janssen; C J Niemegeers; F Awouters; K H Schellekens; A A Megens; T F Meert Journal: J Pharmacol Exp Ther Date: 1988-02 Impact factor: 4.030
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