Evaluation of solid dispersion particles prepared with SEDS

• Published in: International journal of pharmaceutics Vol. 250; no. 2; pp. 385 - 401
• Main Authors: Juppo, Anne Mari, Boissier, Catherine, Khoo, Cynthia
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 16.01.2003; Elsevier
• Subjects: Biological and medical sciences; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Evaluation, Preclinical - methods; DSC; FTIR; General pharmacology; Mannitol - chemical synthesis; Mannitol - chemistry; Medical sciences; Particle; Pharmaceutical Preparations - chemical synthesis; Pharmaceutical Preparations - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymethacrylic Acids - chemical synthesis; Polymethacrylic Acids - chemistry; SEDS; Solid dispersion; Solubility; Supercritical fluid crystallisation; Technology, Pharmaceutical - methods; Particle; Solid dispersion; DSC; Supercritical fluid crystallisation; FTIR; SEDS; Methacrylate polymer; Pharmaceutical technology; Crystallization; Molecular interaction; Dissolution; In vitro; Solid state; Mannitol; Dosage form; Supercritical solvent; Active ingredient; Release
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(02)00577-X

Formation of solid solution particles in the Solution Enhanced Dispersion by Supercritical fluids (SEDS) process from a model drug and two different types of carriers, mannitol and Eudragit® E100 was evaluated. The crystal properties of samples and molecular interactions were investigated with DSC and FTIR, respectively. The effect of co-crystallisation of drug and mannitol on dissolution rate was studied. Even if a true one-phase solid dispersion was not obtained, the crystal structure of both drug and mannitol was mutually affected by the presence of the other. The drug was not in highly crystalline form in the co-precipitates. The interactions between the drug and mannitol could also be identified as hydrogen bonding between the amine or hydroxyl groups of the drug and the hydroxyl groups of mannitol. These interactions and changes in the crystal structure are probably directly related to the increase in the dissolution rate observed. A true solid solution was obtained when the drug was co-processed with Eudragit® E100. A clear interaction between the acid hydroxyl group of the drug and the basic carbonyl group on the Eudragit® E100 was observed. SEDS was shown to be an effective process for forming intimate blends and solid solutions for the drug and two different types of carriers.