H Murakami1, M Kobayashi, H Takeuchi, Y Kawashima. 1. Product & Technology Development Laboratory, Tanabe Seiyaku Co., Ltd. 16-89 Kashima 3-chome, Yodogawa-ku, Osaka, Japan.
Abstract
PURPOSE: The objectives of this study were to prepare the long-acting matrix tablets by direct compression of the mixture of drug and poly(DL-lactide-co-glycolide) (PLGA) nanoparticles and to clarify the effects of such factors as polymer species, mixing ratio of nanoparticles with different molecular weights, and the tablet weight on the drug release and to discuss the mechanism of drug release from matrix tablets. In addition, mini-matrix tablets were prepared to investigate the possibility of application as an implantable dosage form. METHODS: PLGA nanoparticles were prepared by the modified spontaneous emulsion solvent diffusion method. The matrix tablets were prepared by direct compression of mixtures of drug and nanoparticles, and then the release properties, swelling properties and changes in molecular weight of PLGA during the release test were evaluated. RESULTS: The drug showed the biphasic release patterns from all matrix tablets; i.e. a portion of the drug was released rapidly (the initial release phase), the release stopped for a long period (the lag time), and then the residual drug was released (the second release phase). Matrix tablets with various biphasic release patterns could be prepared by altering the molecular weight or copolymer ratio of PLGA. The addition of nanoparticles of low molecular weight PLGA to those of high molecular weight reduced the release rate at the initial release phase, but that at the second release phase was almost entirely unaffected by mixing ratio. Also, the release patterns could be changed by altering the tablet weight and size, but the amounts released per unit of surface area were the same. Hydration analysis suggested that the initial release rates were correlated well with the swelling properties of tablets. CONCLUSION: This system had advantages in terms of simplicity in design and predictability of drug release rate and may be useful as an implantable dosage form.
PURPOSE: The objectives of this study were to prepare the long-acting matrix tablets by direct compression of the mixture of drug and poly(DL-lactide-co-glycolide) (PLGA) nanoparticles and to clarify the effects of such factors as polymer species, mixing ratio of nanoparticles with different molecular weights, and the tablet weight on the drug release and to discuss the mechanism of drug release from matrix tablets. In addition, mini-matrix tablets were prepared to investigate the possibility of application as an implantable dosage form. METHODS: PLGA nanoparticles were prepared by the modified spontaneous emulsion solvent diffusion method. The matrix tablets were prepared by direct compression of mixtures of drug and nanoparticles, and then the release properties, swelling properties and changes in molecular weight of PLGA during the release test were evaluated. RESULTS: The drug showed the biphasic release patterns from all matrix tablets; i.e. a portion of the drug was released rapidly (the initial release phase), the release stopped for a long period (the lag time), and then the residual drug was released (the second release phase). Matrix tablets with various biphasic release patterns could be prepared by altering the molecular weight or copolymer ratio of PLGA. The addition of nanoparticles of low molecular weight PLGA to those of high molecular weight reduced the release rate at the initial release phase, but that at the second release phase was almost entirely unaffected by mixing ratio. Also, the release patterns could be changed by altering the tablet weight and size, but the amounts released per unit of surface area were the same. Hydration analysis suggested that the initial release rates were correlated well with the swelling properties of tablets. CONCLUSION: This system had advantages in terms of simplicity in design and predictability of drug release rate and may be useful as an implantable dosage form.