title: A novel asymmetric membrane osmotic pump capsule with in situ formed delivery orifices for controlled release of gliclazide solid dispersion system.
abstract: In this study, a novel asymmetric membrane osmotic pump capsule of gliclazide (GLC) solid dispersion was developed to achieve a controlled drug release. The capsule shells were obtained by wet phase inversion process using cellulose acetate as semi-permeable membrane, glycerol and kolliphor P188 as pore formers, then filled with the mixture of GLC solid dispersion and pH modifiers. Differentiate from the conventional formulations, sodium carbonate was chosen as the osmotic agent and effervescent agent simultaneously to control the drug release, instead of the polymer materials. The ternary solid dispersion of GLC, with polyethylene glycol 6000 and kolliphor P188 as carriers, was prepared by solvent-evaporation method, realizing a 2.09-fold increment in solubility and dissolution rate in comparison with unprocessed GLC. Influence of the composition of the coating solution and pH modifiers on the drug release from the asymmetric membrane capsule (AMC) was investigated. The ultimate cumulative release of the optimal formulation reached 91.32% in an approximately zero-order manner. The osmotic pressure test and dye test were conducted to validate the drug release mechanism from the AMC. The in vivo pharmacokinetic study of the AMC indicated a 102.66±10.95% relative bioavailability compared with the commercial tablet, suggesting the bioequivalence between the two formulations. Consequently, the novel controlled delivery system with combination of solid dispersion and AMC system is capable of providing a satisfactory alternative to release the water-insoluble drugs in a controlled manner.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: School of Biomedical & Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: yangxg123@163.com.
authors.forename: Xinggang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: pppwwwsss@163.com.
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
mesh_terms: D000818:Animals; D001682:Biological Availability; D002214:Capsules; D002254:Carbonates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D005907:Gliclazide / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D009997:Osmotic Pressure; D011108:Polymers / Q000737:chemistry*; D012995:Solubility
chemical_list: D002214:Capsules; D002254:Carbonates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D007004:Hypoglycemic Agents; D011108:Polymers; C005686:sodium carbonate; D005907:Gliclazide
keywords: Asymmetric membrane capsule; Gliclazide; Osmotic pump; Pharmacokinetic; Solid dispersion; pH modifiers