Formulation of a modified-release pregabalin tablet using hot-melt coating with glyceryl behenate

Abstract

A modified-release (MR) tablet of the anti-anxiety drug pregabalin (PRE) was prepared by hot-melt coating PRE with glyceryl behenate (GB) as a release retardant and compressing to form a matrix with microcrystalline cellulose (MCC) as a hydrophilic diluent. GB-coated PRE had a size in the range of 177-290 mm with good to acceptable flowability. Tablet hardness decreased slightly as GB content increased. PRE release from the tablet matrices was successfully modified by altering the ratio of MCC and GB, and it was found that dissolution-or diffusion-controlled release depended on the amount of GB used. Drug release was pH-independent. An accelerated stability test on the most promising MR tablet at 40 degrees C and 75% relative humidity for 6 months showed no significant changes in PRE content, and the occurrence of total impurities-including PRE-lactam-was within acceptable limits. After oral administration of the selected MR tablet or a commercial IR capsule (Lyrica) to healthy human volunteers, pharmacokinetic parameters including T-max, C-max, AUC(0-24), and T-1/2 were compared. The confidence interval of AUC(0-24) was within the adequate range, but that of C-max was inadequate. This study demonstrated the potential use of GB for PRE-containing MR formulations. (C) 2015 Elsevier B.V. All rights reserved.