title: Effects of polyvinylpyrrolidone both as a binder and pore-former on the release of sparingly water-soluble topiramate from ethylcellulose coated pellets.
abstract: Delivering sparingly water-soluble drugs from ethylcellulose (EC) coated pellets with a controlled-release pattern remains challenging. In the present study, hydrophilic polyvinylpyrrolidone (PVP) was used both as a binder and a pore-former in EC coated pellets to deliver sparingly water-soluble topiramate, and the key factors that influenced drug release were identified. When the binder PVP content in drug layers below 20% w/w was decreased, the physical state of topiramate changed from amorphous to crystalline, making much difference to drug solubility and dissolution rates while modifying the drug release profile from first-order to zero-order. In addition, without PVP in drug layering solution, drug layered particles were less sticky during layering process, thus leading to a shorter process and higher loading efficiency. Furthermore, PVP level as a pore-former in EC coating layers mainly governed drug release from the coated pellets with the sensitivity ranging from 23% to 29%. PVP leaching rate and water permeability from EC/PVP film increased with the PVP level, which was perfectly correlated with drug release rate. Additionally, drug release from this formulation was independent of pH of release media or of the paddle mixing speed, but inversely proportional to the osmolality of release media above the physiological range.
authors: Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors: Meiyan
authors: M
authors: Yang
authors: Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China; School of Pharmacy, Central South University, Changsha 410013, PR China.
authors: Si
authors: S
authors: Xie
authors: Life Science and Bio-engineering College, Beijing University of Technology, Beijing 100022, PR China.
authors: Qiu
authors: Q
authors: Li
authors: Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors: Yuli
authors: Y
authors: Wang
authors: Pharmaceutical College, Henan University, Kaifeng 475004, PR China.
authors: Xinyi
authors: X
authors: Chang
authors: Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors: Li
authors: L
authors: Shan
authors: Pharmaceutical College, Henan University, Kaifeng 475004, PR China.
authors: Lei
authors: L
authors: Sun
authors: Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China; School of Pharmacy, Central South University, Changsha 410013, PR China.
authors: Xiaoli
authors: X
authors: Huang
authors: Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China. Electronic address: gaocs@bmi.ac.cn.
authors: Chunsheng
authors: C
authors: Gao
mesh_terms: D000927:Anticonvulsants / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004337:Drug Carriers; D004343:Drug Implants; D005632:Fructose / Q000031:analogs & derivatives* / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008956:Models, Chemical; D009994:Osmolar Concentration; D016062:Porosity; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D000077236:Topiramate; D014867:Water / Q000737:chemistry*
chemical_list: D000927:Anticonvulsants; D004337:Drug Carriers; D004343:Drug Implants; D014867:Water; D000077236:Topiramate; D005632:Fructose; C013517:ethyl cellulose; D002482:Cellulose; D011205:Povidone
keywords: Binder; Drug release mechanism; PVP K30; Pore-former; Sparingly water-soluble drug; Topiramate