title: Intraorally fast-dissolving particles of a poorly soluble drug: preparation and in vitro characterization.
abstract: In this study, the dissolution rate of a poorly soluble drug, perphenazine (PPZ) was improved by a solid dispersion technique to permit its usage in intraoral formulations. Dissolution of PPZ (4 mg) in a small liquid volume (3 ml, pH 6.8) within one minute was set as the objective. PVP K30 and PEG 8000 were selected for carriers according to the solubility parameter approach and their 5/1, 1/5 and 1/20 mixtures with PPZ (PPZ/polymer w/w) were prepared by freeze-drying from 0.1 N HCl solutions. The dissolution rate of PPZ was improved with all drug/polymer mixture ratios compared to crystalline or micronized PPZ. A major dissolution rate improvement was seen with 1/5 PPZ/PEG formulation, i.e. PPZ was dissolved completely within one minute. SAXS, DSC and XRPD measurements indicated that solid solutions of amorphous PPZ in amorphous PVP or in partly amorphous PEG were formed. DSC and FTIR studies suggested that PPZ dihydrochloride salt was formed and hydrogen bonding was occurred between PPZ and the polymers. It was concluded that molecular mixing together with salt formation promoted the dissolution of PPZ, especially in the case of the 1/5 PPZ/PEG dispersion, making it a promising candidate for use in intraoral formulations.
authors.affiliation: Department of Pharmaceutics, University of Kuopio, Kuopio, Finland. riikka.laitinen@uku.fi
authors.forename: Riikka
authors.initials: R
authors.lastname: Laitinen
authors.forename: Eero
authors.initials: E
authors.lastname: Suihko
authors.forename: Kaisa
authors.initials: K
authors.lastname: Toukola
authors.forename: Mikko
authors.initials: M
authors.lastname: Björkqvist
authors.forename: Joakim
authors.initials: J
authors.lastname: Riikonen
authors.forename: Vesa Pekka
authors.initials: VP
authors.lastname: Lehto
authors.forename: Kristiina
authors.initials: K
authors.lastname: Järvinen
authors.forename: Jarkko
authors.initials: J
authors.lastname: Ketolainen
mesh_terms: D000284:Administration, Oral; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D005612:Freeze Drying; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D010546:Perphenazine / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D053838:Scattering, Small Angle; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D014150:Antipsychotic Agents; D004337:Drug Carriers; D011092:Polyethylene Glycols; D010546:Perphenazine; D011205:Povidone