Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Regular Articles
Development of an Extended-Release Formulation for Apremilast and a Level A in Vitroin Vivo Correlation Study in Beagle Dogs
Meiqiong TangPing Hu Shigui HuangQiang ZhengHao YuYun He
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2016 Volume 64 Issue 11 Pages 1607-1615


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 (r2 up 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 tmax and t1/2, lower Cmax and 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.

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© 2016 The Pharmaceutical Society of Japan
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