The Studies On The Sustained-Release Dropping Pills Of Dipyridamole

Dropping pills is a solid dispersion with solid or liquid drug melt in matrix, and being dropped into the cooling agent then contract into pill which has the advantages of a large surface area, low gastrointestinal irritation, high bioavailability and productivity.In this thesis, we prepared sustained-release dropping pills using dipyridamole (DIP) as the model drug. We studied the formula and forming technology according to the results of the preliminary test; the orthogonal experiment was carried out to select the formation according to the rate of accretio,qualification of circular ,the RSD of weight ,and optimal formula by hardness and drug release. The quality of the sustained-release dropping pills was evaluated, and study on pharmacokinetics was carried out in animal experiments.First, method was established to determine DIP by ultraviolet spectrophotometry which was accurate, sensitive and could be used in determiantion of content and drug release.The optimum formulation for DIP dropping pills was PEG20000(3g): PEG6000(6g):SA(5.7g):Eudragit L100(0.4g):GMS(2.9g): DIP(2g). Drug released from the dropping pills could be sustained for 12h in vitro and there was no obvious difference between releasing behavior in medium with pH1.2 and pH6.8. The friability was 0.61%±0.07%.Investigation on drug release was carried out in vitro and the curve fitting method was used to find the drug release equation. The DIP release behavior from dropping pills followed the zero-order kinetics between 0～2h and first-order kinetics between 3～12h.Quality of the sustained-release dropping pills was evaluated by DSC and IR combined with microscope .The results showed that DIP was of amorphous state in matrix and formed solid dispersion. Results of the stability experiments indicated that the pills could be kept stable at(40±2)℃,RH(75±5)% for 6 months.An HPLC method for determination of DIP in rabbits plasma was established. Double cycle crossover with single oral dose was performed to investigate pharmacokinetics and relative bioavailability in rabbits using common tablets as control. The data were processed using 3p87 pharmacokinetic program. Significant deviation in bioavailability was observed between common tablet and DIP dropping pills.