Studies On The Preparation,Quality Control And Pharmacokinetics Of IDHP Dropping Pills

Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxy-propanoate (IDHP) is a major bioactive metabolite of danshen following oral administration of composite danshen dropping pills. It is potentially effective for the treatment of myocardia ischemia and anoxia. In this study, dropping pill was chosen as the IDHP dosage form, and the formula and preparation of IDHP dropping pills were optimazed. And then the quality control method were investigated for the IDHP dropping pills. Furthermore, the pharmacokinetic experiments were undertaken to assess delivery characteristics of IDHP in rats following a single oral and sublingual administration.1. The response surface methodology was used to optimize the formula of IDHP dropping pills, with sphericity, hardness, apparence, weight variation and disintegration time as experimental criterion. The process factors, such as dropping temperature, cooling temperature, dropping speed, were also screened. The optimal formula of IDHP dropping pills was as follows:drug loading rate was 23.0%, starch content was 14.0%, CMS-Na was 4.0% and PEG6000 was 59.0%. Preparation was performed according to following condition: dropping temperature was 80, cooling temperature was range from 1 to 5"C, and dropping speed was 30 drops/min. The verificat?ion and influence factor tests were provided and the results showed that the IDHP dropping pills had good forming quality, and conformed to the quality standards involving disintegration time, content determination and it's related substances.2. The quality control standard of IDHP pills was established including weight variation, disintegration time, content determination and related substances. HPLC method was adopted to determine the contents of IDHP and it's related substances in the dropping pills, which had a good repeatability and recovery in terms of methodological evaluation. The results showed that the contents of related substance in the three batches of pill samples were less than 3% of IDHP contents, while IDHP contents were 90.0%?110.0% of the labeled amount.3. HPLC-MS method was established for determination IDHP in rat plasma. After a single oral, sublingual and intravenous administration, rat plasma samples were taken and the concentration of IDHP was determined. The results showed that the peak time(Tmax) following sublingual administration was 20 min, whereas that of oral IDHP was 30 min. Moreover, the calculated AUC of sublingual administration was higher than that of oral administration. Consequently, the bioavailability of sublingual IDHP(42.26%) was significantly higher than that of oral IDHP (24.23%).