title: Development of an Extended-Release Formulation for Apremilast and a Level A in Vitro-in Vivo Correlation Study in Beagle Dogs.
abstract: The primary objective of the present study was to develop extended-release matrix formulations of apremilast for the oral delivery and to study their in vitro and in vivo correlation. Five extended-release formulations containing hydroxypropylmethylcellulose (HPMC) as the retarding excipient with different release rate of apremilast were prepared. Dissolution tests of all the formulated tablets were performed in water, pH 4.0 and 6.8 buffer solutions. The in vitro release kinetics was studied and supported by Korsmeyer-Peppas's equation as it presented highest values of correlation coefficients (r2up to 0.966). Among all formulated tablets, F2 (HPMC 25%) and F4 (HPMC 35%) were selected to perform an in vivo study in beagle dogs to obtain various pharmacokinetic parameters, i.e., peak plasma concentration (Cmax), time to peak plasma concentration (tmax), area under the plasma-concentration vs. time curve (AUC). Higher tmaxand t1/2, lower Cmaxand elimination coefficient (Ke) were observed for both extended formulations compared to marketed immediate-release products (Otezla®). Level A in vitro-in vivo correlations were created with the help of Wagner-Nelson and numeric deconvolution methods. Both formulations showed good in vitro-in vivo correlations whose accuracies were further verified by an internal validation.
authors: College of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing University.
authors: Meiqiong
authors: M
authors: Tang
authors: Ping
authors: P
authors: Hu
authors: Shigui
authors: S
authors: Huang
authors: Qiang
authors: Q
authors: Zheng
authors: Hao
authors: H
authors: Yu
authors: Yun
authors: Y
authors: He
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004285:Dogs; D065546:Drug Liberation; D013607:Tablets; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D013607:Tablets; D013792:Thalidomide; C505730:apremilast