title: Organic-aqueous crossover coating process for the desmopressin orally disintegrating microparticles.
abstract: The purpose of the present study was to prepare desmopressin orally disintegrating microparticles (ODMs) using organic-aqueous crossover coating process which featured an organic sub-coating followed by an aqueous active coating. Sucrose beads and hydroxypropyl cellulose (HPC) were used as inert cores and a coating material, respectively. Characterizations including size distribution analysis, in-vitro release studies and in-vitro disintegration studies were performed. A pharmacokinetic study of the ODMs was also conducted in eight beagle dogs. It was found that sucrose beads should be coated using organic solvents to preserve their original morphology. For the active coating, the aqueous coating solution should be used for drug stability. When sucrose beads were coated using organic-aqueous crossover coating process, double-layer ODMs with round shapes were produced with detectable impurities below limit of US Pharmacopeia. The median size of ODMs was 195.6 μm, which was considered small enough for a good mouthfeel. The ODMs dissolved in artificial saliva within 15 s because of hydrophilic materials including sucrose and HPC in the ODMs. Because of its fast-dissolving properties, 100% release of the drug was reached within 5 min. Pharmacokinetic parameters including Cmax and AUC24 indicated bioequivalence of the ODMs and the conventional immediate release tablets. Therefore, by using the organic-aqueous crossover coating process, double-layer ODMs were successively prepared with small size, round shapes and good drug stability.
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon , Republic of Korea .
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Kyu-Mok
authors.initials: KM
authors.lastname: Hwang
authors.forename: Chun-Woong
authors.initials: CW
authors.lastname: Park
authors.forename: Yun-Seok
authors.initials: YS
authors.lastname: Rhee
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D000818:Animals; D050034:Antidiuretic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018592:Cross-Over Studies; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004285:Dogs; D004304:Dosage Forms; D004355:Drug Stability; D005079:Excipients / Q000008:administration & dosage; D008297:Male; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D013810:Therapeutic Equivalency
chemical_list: D050034:Antidiuretic Agents; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D005079:Excipients; D003894:Deamino Arginine Vasopressin
keywords: Aqueous active coating process; double-layered microparticles; fluidized-bed coating; nocturnal enuresis; sucrose beads