Masazumi Kojima

Development of controlled release matrix pellets by annealing with micronized water-insoluble or enteric polymers

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.

Effect of the type of lubricant on the characteristics of orally disintegrating tablets manufactured using the phase transition of sugar alcohol

The aim of this study was to evaluate the effect of lubricants on the characteristics of orally disintegrating (OD) tablets manufactured using the phase transition of sugar alcohol. OD tablets were produced by directly compressing a mixture containing lactose-xylitol granules, disintegrant, glidant and lubricant, and subsequent heating. The effect of the type of lubricant on the tablet characteristics was evaluated using magnesium stearate (Mg-St), sodium stearyl fumarate (SSF), and talc as lubricants. The hardness of the tablets increased to ca. 6kp as a result of heating, regardless of the kind of lubricant. The oral disintegration time of the tablets containing Mg-St or SSF increased with an increase in the hardness. In contrast, the oral disintegration time of the tablets containing talc was not changed despite of an increase in hardness. The water absorption rate of the tablets containing talc was much faster than that of the tablets containing other lubricants. The surface free energy measurement showed that the polarity of the tablet components containing talc was remarkably increased by heating. The water absorption rate of the tablets containing talc was also increased by heating. These results indicate that a more hydrophilic surface might be attained by heating the talc. Consequently, talc was demonstrated to be the most desirable lubricant for the preparation of OD tablets based on the principle of the phase transition of sugar alcohol.