In vitro-in vivo correlations of scalable PLGA-risperidone implants for the treatment of schizophrenia.
OBJECTIVE
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.


CONCLUSIONS
Data demonstrate the applicability of our modeling system and advance long-term, implantable antipsychotics toward clinical application.
Amann
Laura C
LC
Translational Neuroscience Program, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Gandal
Michael J
MJ
Lin
Robert
R
Liang
Yuling
Y
Siegel
Steven J
SJ
D020341:Absorbable Implants; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage; D016503:Drug Delivery Systems; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D023421:Models, Animal; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000008:administration & dosage*; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D018967:Risperidone