title: Stabilization of hot-melt extrusion formulations containing solid solutions using polymer blends.
abstract: This study was aimed at enhancing the physical stability of the drug clotrimazole (CT) and the polymer contained within hot-melt extrusion (HME) films using polymer blends of hydroxypropyl cellulose (HPC) and poly(ethylene oxide) (PEO). The HME films were investigated for solid-state characteristics, moisture sorption, bioadhesivity, mechanical properties, glass transition temperature, release characteristics, and physical and chemical stability of the drug and the polymer within the HME films. The solid-state characterization of the drug and the polymer was performed using differential scanning calorimetry, x-ray diffractometry, and dynamic mechanical analysis. A texture analyzer was used to study the bioadhesive and mechanical properties of the HME films. The physical and chemical stability of the films, stored at 25 degrees C/60% relative humidity or in a desiccator, was studied for up to 12 months. CT was found to be in solid solution within all of the formulations extruded. The physical stability of the drug and PEO in the HME films increased with increasing HPC concentration, but the bioadhesivity and flexibility of the PEO films decreased with increasing HPC concentration. Films containing HPC:PEO:CT in the ratio of 55:35:10 demonstrated optimum physical-mechanical, bioadhesive, and release properties. In conclusion, polymer blends of HPC and PEO were used successfully to tailor the drug release, mechanical and bioadhesive properties, and stability of the HME films.
authors.affiliation: Food and Drug Administration, Division of Pharmaceutical Analysis, St Louis, MO 63101, USA.
authors.forename: Suneela
authors.initials: S
authors.lastname: Prodduturi
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Urman
authors.forename: Joshua U
authors.initials: JU
authors.lastname: Otaigbe
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
mesh_terms: D001696:Biomechanical Phenomena; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003022:Clotrimazole / Q000008:administration & dosage* / Q000737:chemistry; D004355:Drug Stability; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D011092:Polyethylene Glycols; D002482:Cellulose; C008079:hydroxypropylcellulose; D003022:Clotrimazole