title: In vitro-in vivo correlation of parenteral risperidone polymeric microspheres.
abstract: The objective of the present study was to determine whether an in vitro-in vivo correlation (IVIVC) can be established for polymeric microspheres that are equivalent in formulation composition but prepared with different manufacturing processes. Risperidone was chosen as a model therapeutic and poly(lactic-co-glycolic acid) (PLGA) with similar molecular weight as that used in the commercial product Risperdal® Consta® was used to prepare risperidone microspheres. Various manufacturing processes were investigated to produce the risperidone microspheres with similar drug loading (approx. 37%) but distinctly different physicochemical properties (e.g. porosity, particle size and particle size distribution). In vitro release of the risperidone microspheres was investigated using different release testing methods (such as sample-and-separate and USP apparatus 4). In vivo pharmacokinetic profiles of the risperidone microsphere formulations following intramuscular administration were determined using a rabbit model. Furthermore, the obtained pharmacokinetic profiles were deconvoluted using the Loo-Riegelman method and the calculated in vivo release was compared with the in vitro release of these microspheres. Level A IVIVCs were established and validated for the compositionally equivalent risperidone microspheres based on the in vitro release data obtained using USP apparatus 4. The developed IVIVCs demonstrated good predictability and were robust. These results showed that the developed USP apparatus 4 method was capable of discriminating PLGA microspheres that are equivalent in formulation composition but with manufacturing differences and predicting their in vivo performance in the investigated animal model.
authors.affiliation: School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD 20993, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Choi
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD 20993, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Qu
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD 20993, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA. Electronic address: d.burgess@uconn.edu.
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Burgess
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D011817:Rabbits; D018967:Risperidone / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D018967:Risperidone
keywords: In vitro and in vivo correlation; Level A; Manufacturing differences; Poly(lactic-co-glycolic acid) (PLGA) microspheres; Risperidone; USP apparatus 4