title: Controlled delivery of carvedilol nanosuspension from osmotic pump capsule: in vitro and in vivo evaluation.
abstract: This study intended to develop a novel controlled delivery osmotic pump capsule of carvedilol nanosuspension. The capsule is assembled using a semi-permeable capsule shell with contents including nanosuspension drying powder, mannitol and Plasdone S-630. The physical characteristics of semi-permeable capsule walls were compared among different coating solutions under different temperature. The composition of the coating solution and drying temperature appeared to be important for the formation of the shells. Carvedilol nanosuspension was prepared by precipitation-ultrasonication technique and was further lyophilized. Response surface methodology was used to investigate the influence of factors on the responses. The optimized formulation displayed complete drug delivery and zero-order release rate. The TEM and particle size analysis indicated that the morphology of the resultant nanoparticle in the capsule was spherical shaped with a mean size of 252±19 nm. The in vivo test in beagle dogs demonstrated that the relative bioavailability of the novel system was 203.5% in comparison to that of the marketed preparation. The capsule successfully controlled the release of carvedilol and the fluctuation of plasma concentration was minimized. The system is a promising strategy to improve the oral bioavailability for poorly soluble drugs and preparing it into elementary osmotic pump conveniently.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China; School of Biomedical & Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China. Electronic address: liudandan1124@126.com.
authors.forename: Dandan
authors.initials: D
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Lyu
authors.affiliation: School of Biomedical & Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Bai
authors.affiliation: School of Biomedical & Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China.
authors.forename: Huiqi
authors.initials: H
authors.lastname: Ge
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Xinggang
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: pwstfzy@163.com.
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D002227:Carbazoles / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004285:Dogs; D016503:Drug Delivery Systems; D065546:Drug Liberation; D008353:Mannitol / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D009995:Osmosis; D010316:Particle Size; D011205:Povidone / Q000737:chemistry; D011412:Propanolamines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility
chemical_list: D000959:Antihypertensive Agents; D002227:Carbazoles; D003692:Delayed-Action Preparations; D011412:Propanolamines; D000077261:Carvedilol; D008353:Mannitol; D011205:Povidone
keywords: Carvedilol; Central composite design; Nanosuspensions; Oral bioavailability; Osmotic pump; Poorly water-soluble drugs