Study On Sustained Release Tablets Of Rotundine

Rotundine is a dopamine receptor antagonist, which was accepted as an anodyne by Pharmacopoeia of China. As an anodyne, its efficacy is almost the same as tramadol but with no addiction and little side effect such as queasiness and spew. In addition, it is also effective for insomnia. Its injection and conventional tablets have come into the market already. However, it was almost out of use in clinics because of its side effect of sleepiness when used as an anodyne and its frequency of use everyday.In order to prolong the therapy effect of alleviation and fully make use of its side-effect of hypnosis, we planned a study on rapid-release and sustained release double-layer tablets of rotundine, which was really a convenience for those who not only need alleviating but also need calming down. Study of this had not been reported previously.The optimization of the formulation was the key work in this study. Firstly, after adjusting of dosage, selecting of excipients and studying on the stability of rapid-release layer, we got the optimal formulation of sustained release tablets. Secondly, we established a reliable UV method for the determination of rotundine, checked with good accuracy and repeatability. In vitro evaluation indicated the dissolution of rotundine from sustained release formulation was pH-dependent and the release kinetics of the formulation in different medias differed. Finally, a series of samples were prepared for quality criterion study, stability study and oral pharmacokinetics investigation. The results showed that the formulations of sustained release tablets were reasonable, simple and convenient to prepare, with good reproducibility.A method for the stability study of rotundine was developed. The stability study on sustained release tablets indicated that the tablets were stable, nearly without any changes during the stability study.Based on the study of formulation and stability, quality criterion study was put forward. The result showed that drafts of quality criterion for sustained release tablets could well control the quality of products.The pharmacokinetics and bioavailability study of the sustained release tablets of rotundine was carried out on 6 Beagle dogs in a randomized crossover manner. Serum samples were assayed for rotundine using a high-performance liquid chromatography (HPLC) method with UV detection. The results were as follows: The concentration-time curves conformed to 2-compartment model with first-order absorption. The t_max and C_max of sustained release tablets was 0.67h and 1167.2ng/mL respectively. The difference of t_1/2β and MRT between sustained release tablets and conventional tablets had no significant, but the C_max between sustained release tablets and conventional tablets had distinct difference, thus demonstrating sustained release...