title: Development of controlled release matrix pellets by annealing with micronized water-insoluble or enteric polymers.
abstract: The purpose of this study was to develop a new method for preparing controlled release (CR) matrix pellets by annealing with water-insoluble polymers, and to elucidate a relationship between the annealing temperature of the matrix pellets and a glass transition temperature (T(g)) or a minimum film-forming temperature (MFT) of the polymer/plasticizer systems that constituted the matrix pellets. The pellets containing theophylline as a model drug were prepared by the extrusion-spheronization method and subsequent annealing. The pellets were characterized mainly by pellet formation, release studies, and thermal evaluations. It was apparent that the annealing temperature for the CR matrix pellets was related to the T(g) and MFT of the polymer/plasticizer systems. For ethylcellulose (EC) containing 22.7% triethylcitrate (TEC), the annealing temperature required for preparing CR pellets was 80 degrees C, which was more than 20 degrees C higher than the T(g) and MFT of this EC/TEC system. In contrast, hydroxypropylmethylcellulose acetate succinate (HPMCAS) containing 22.7% TEC could be used to prepare CR pellets without heating. The T(g) of this HPMCAS/TEC system was about 60 degrees C and the MFT was lower than 20 degrees C, indicating that water can act as a plasticizer for HPMCAS and that HPMCAS/TEC pellets could be annealed at room temperature. These results suggest that MFT is a better indicator than T(g) for estimating annealing temperature. SEM observation showed that the EC/TEC pellets annealed at 80 degrees C had a matrix structure with coalesced particles. On the contrary, unannealed pellets consisted of individually distinguishable particles. The release rate of drug from the matrix CR pellets was dependent on the drug concentration and polymer to plasticizer ratio.
authors.affiliation: Tokyo Pharmaceutical Research Center, Pharmaceutical Technology Research Laboratories, Daiichi Pharmaceutical Co., Ltd., 16-13 Kita-Kasai, 1-Chome, Edogawa-ku, Tokyo, 134-8630, Japan. kojimsnr@daiichipharm.co.jp
authors.forename: Masazumi
authors.initials: M
authors.lastname: Kojima
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakagami
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D004343:Drug Implants / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients; D006244:Hardness; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013696:Temperature; D013806:Theophylline / Q000737:chemistry; D014867:Water; D014961:X-Ray Diffraction
chemical_list: D004343:Drug Implants; D005079:Excipients; D011108:Polymers; D014867:Water; C048331:hydroxypropylmethylcellulose acetate succinate; C013517:ethyl cellulose; D002482:Cellulose; D008747:Methylcellulose; D013806:Theophylline