The formulation study of dipyridamole pellet dosage form

• Main Authors: Yeong-tseun Lin, 林泳村
• Other Authors: Ming-Thau Sheu
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/95073961866618691888

碩士 === 台北醫學院 === 藥學研究所 === 88 === ABSTRACT Pellets as a drug delivery system offer not only therapeutic advantages such as less irritation of the gastro-intestinal tract and a lowered risk of side effects due to dose dumping but also technological advantages. The purpose of this research was to develop a controlled release pellet dosage form for poorly water-soluble drug with high dose. Dipyridamole was selected as a model drug and the commercial product, Pertsantin® was marked as reference product. The release profile of dipyridamole from a commercial product, Persantin, was examined for reference. There are two parts in this study. One is the preparation of pellets and the other is the coating of controlling film on the pellet. In the preparation of pellets, microcrystalline cellulose (MCC), lactose anhydrate and low-substituted hydroxypropylcellulose (LHPC-LH21) were used as excipient. The production of pellets was done by means of the Extruder-Spheronizer. In order to increase the dissolution of dipyridamole (pKa 6.4) in basic environment, simulated intestinal fluid containing 0.25% sodium lauryl sulfate was selected as a medium. The characteristics of pellets were evaluated by the yield and roundness of pellets. With an increasing ratio of MCC to lactose anhydrate, the yield and roundness of pellets were gradually improved but the extent of dipyridamole release was apparently decreased. The formulation 9 with the excipent mixtures (MCC : lactose anhydrate = 2 : 8) showed a similar dissoluton rate as that for Persantin. The yield of pellets prepared using lactose anhydrate and LHPC-LH21 was increased with increasing stirring time and the amount of water added. With the addition of PEG 6000 as plasticizer and Prmojel as disintegrant to pellets, the dissolution rate of drug from pellets was promoted and the yield of preparation was enhanced as well. The closeness of the dissolution profile to that of Persantin was demonstrated by the formulation with the presence of 7.5% Primojel and 1% PEG 6000 in the pellet containing MCC, lactose anhydrate, and LHPC-LH21 at a mixing ratio of 2 : 5 : 3. Besides that, the formulation with the presence of 5% Primojel and 0.5% PEG 6000 in the pellet containing MCC and lactose anhydrate at a mixing ratio of 3:7 also showed the similar dissolution profile. Two pellet formulations mentioned above were selected as core pellets to further coat with Eudragit 30D-55 and ethylcellulose using a fluidized-bed coating system. The dissolution profiles of dipyridamole from pellet coated with Eudragit 30D-55 and ethylcellulose were evaluated in the simulated gastric fluid. The results showed a release profile of dipyridamole in the medium of simulated gastric fluid was close to that for Persantin.