Formulation And Studies Of Gastrointestinal Bioadhesive Capsule Of Cantharidin

Objective:Cantharidin is a cyclic monoterpene that was extracted from the Chinese Mylabris. The shortcoming of Cantharidin such as poision, solution, half life period and irritability to the digestive system restrict it’s utilization in the clinical practice even though it has strong effect on the tumour cell. The adhesive material and compound material were applied in this procedure and the contemporary technique was applied in this study to make gastrointestinal bioadhesive capsule that it could control the release rate, reduce the side effect, increase the absorption by the means of the extention of the residence’s time in the digestive system and enhance the compliance of paients.Methods:1 Preparation of gastrointestinal bioadhesive capsule of Cantharidin: The adhesive material was selected and the composition, proportion of adhesive materials was decided by the means of the adhesive experiment. The pharmaceutical adjuvant was selected through the release experiment. The optimal formulation was selected based on the orthogonal experimental design of three factor and three levels through the release experiment. The procedure was described in brief as follows: Cantharidin and adjuvant were dealed and blended, then the mixed material was crushed by the instrument, granules were compressed into 3 millimetre tablets, finally, the tablets were filled into zero-capsule.2 Research on quality control of gastrointestinal bioadhesive capsule of Cantharidin: The HPLC methods were established respectively to determine the content, content uniformity, release rate of the capsule, as well a series of methodological studies were carried out. The stability of the gastrointestinal bioadhesive capsule of Cantharidin, which were based on the proper formula, were studied on the indexs of appearance, content, content uniformity, release rate of the capsule by stress testing and accelerated testing.3 Reach on gastrointestinal bioadhesive capsule of Cantharidin in vivo of the Wistar and Beagle: The studies of the residence of the bioadhesive capsule and the non bioadhesive one in the Wistar mouse’s alimentary tract were carried out. The pharmacokinetics’ s character of the bioadhesive and non bioadhesive were studies in Beagle dog’s vivo. GC method was estabilished to determind the concentration of Cantharidin in plasma. The single dose, two-treatment, two-sequence and randomized crossover study on four adult Beagle dogs were carried out to its’ pharmacokinetics, bioailability and bioequivalence.Results:1 Carbomer 934 p and Chitosan were selected from a serial of bioadhesive material and the proportion, 1:1, of the two adhesive materials and the amount in the formulation were decided by the means of the adhesive experiment. Select Betacyclodextrin as inclusion’s material to include cantharidin by the drug’s release test; The best formulation of gastrointestinal bioadhesive capsule of Cantharidin were selected as follow: Cantharidin 5mg, Carbomer 934 p 50mg, Chitosan 50 mg, Betacyclodextrin 175 mg, PVPP 80 mg, Magnesium stearate 3mg.2 The methods by HPLC were established respectively to determine the content, content’s uniformity and release rate of gastrointestinal bioadhesive capsule of Cantharidin with the detection wavelength of 220 nm. There is no interference on this condition through the methodological verification. The study on methodololgy showed that Cantharidin concentration and the absorption had a good linear relationship in the concentration’s range of 5μg·ml-1~ 75μg·ml-1, precision, recovery and stability all met the requirements, the method could be applied to determine the quality of astrointestinal bioadhesive capsule of Cantharidin.3 The gastrointestinal bioadhesive capsule of Cantharidin were no obvious change on appearance, content, release rate under the special condition of high temperature(60℃), strong light(4500lx) and accelerated testing. However the capsule and the content were severe moisture when it was exposed in high huminity(RH 92.5%), it was still moisture when it was in RH 75%. It should protect against the high humidity during the manufacture and store.4 The method by GC was established to determine the concentration of gastrointestinal bioadhesive capsule of Cantharidin in Beagle dog’s plasma. There is no interference on this condition through the methodological verification. The result of Beagle pharmacokimetics showed that there were significant distinguish between the bioadhesive and non bioahesive capsule on CmaxT,max,AUC0→∞.Conclusion:The formulation and the manufacture process of the gastrointestinal bioadhesive capsule of Cantharidin were simple and feasible and had a good repeatlibility. This study show the gastrointestinal bioadhesive capsule of Cantharidin could extent the residence’s time in alimentary tract, control the release rate reduce the side effects and improve the compliance of paients. The experiment show that there were significant distinguish between the trial capsule and the contrast capsule on Cmax,Tmax,AUC0→∞ in Beagle dog vivo. So the gastrointestinal bioadhesive capsule of Cantharidin had more super than the non bioadhesive one.