In Vitro–In Vivo Correlations of Scalable PLGA-Risperidone Implants for the Treatment of Schizophrenia
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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).
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
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.
Data demonstrate the applicability of our modeling system and advance long-term, implantable antipsychotics toward clinical application.
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- In Vitro–In Vivo Correlations of Scalable PLGA-Risperidone Implants for the Treatment of Schizophrenia
Volume 27, Issue 8 , pp 1730-1737
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- 1. Translational Neuroscience Program, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
- 3. Medical Scientist Training Program, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
- 4. Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
- 2. Department of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
- 5. Department of Psychiatry, Translational Research Laboratories, University of Pennsylvania, Rm. 2202, 125 S. 31st Street, Philadelphia, Pennsylvania, 19104, USA