title: 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 μm 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°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 Tmax, Cmax, AUC0-24, and T1/2 were compared. The confidence interval of AUC0-24 was within the adequate range, but that of Cmax was inadequate. This study demonstrated the potential use of GB for PRE-containing MR formulations.
authors: Drug Delivery Research Laboratory, College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors: Kyu Ho
authors: KH
authors: Jeong
authors: Drug Delivery Research Laboratory, College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors: Hye Seung
authors: HS
authors: Woo
authors: Drug Delivery Research Laboratory, College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors: Chae Jin
authors: CJ
authors: Kim
authors: Drug Delivery Research Laboratory, College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors: Kyung Hwa
authors: KH
authors: Lee
authors: Research Laboratories, ILDONG Pharmaceutical Co., Ltd., Hwaseong-si, Gyeonggi-do 445-170, Republic of Korea.
authors: Jun Young
authors: JY
authors: Jeon
authors: Research Laboratories, ILDONG Pharmaceutical Co., Ltd., Hwaseong-si, Gyeonggi-do 445-170, Republic of Korea.
authors: Sang Young
authors: SY
authors: Lee
authors: Research Laboratories, ILDONG Pharmaceutical Co., Ltd., Hwaseong-si, Gyeonggi-do 445-170, Republic of Korea.
authors: Jae-Hoon
authors: JH
authors: Kang
authors: College of Pharmacy, Keimyung University, Daegu 704-701, Republic of Korea.
authors: Sangkil
authors: S
authors: Lee
authors: Drug Delivery Research Laboratory, College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul 156-756, Republic of Korea. Electronic address: ywchoi@cau.ac.kr.
authors: Young Wook
authors: YW
authors: Choi
mesh_terms: D000328:Adult; D014151:Anti-Anxiety Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D065546:Drug Liberation; D004355:Drug Stability; D005227:Fatty Acids / Q000737:chemistry*; D064368:Healthy Volunteers; D006358:Hot Temperature; D006801:Humans; D008297:Male; D000069583:Pregabalin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D055815:Young Adult
chemical_list: D014151:Anti-Anxiety Agents; D003692:Delayed-Action Preparations; D005227:Fatty Acids; D013607:Tablets; C086409:glyceryl behenate; D000069583:Pregabalin; D002482:Cellulose; C109691:microcrystalline cellulose
keywords: Drug release; Glyceryl behenate; Hot-melt coating; Pharmacokinetic; Pregabalin; Stability