Preparation And Quality Standard Making Of Arecoline And Its Tablets

Arecoline is one of the most active componets of areca-nut. It's pharmacological research results show that it has a good effect on expelling parasites, improving movement of gastrointestinal Smooth Muscle. In the veterinary clinic, arecoline is mainly for the treatment of tapeworm infection on animals. Arecoline obtained mainly through extraction from areca, but the content of Arecoline in the areca-nut was low and the extraction ratio of traditional extraction method was also low. So its clinical application greatly limited by such reason. Based on previous studies, the synthetic technology of arecoline was optimized and its tablets were prepared in this experiment, the stability and quality control of arecoline were also studied. This study resoved preparation of arecoline and its tablets, developed the draft quality standards, promoted the exploitation and wider application of arecoline.The new technology adopted methyllnicotinate repassed N- methylation generated N-methyl iodinated Methyllnicotinated ammonium salt and then reducted by liquefaction sodium borohydride produced Arecoline. The result showed the preparing technology of small batches of arecoline was stable and the total yield is not affected, the content was up to above 95%. This new technology was easy converted to massive product.RP-HPLC method was used for the determination of arecoline hydrobromide, the results showed that this method was simple, fast, specificity, reproducibility and can be used to control the quality of arecoline hydrobromide effectively.Orthogonal experimental design method and the single-factor study were used to analysis the effects on the tablet preparation. The best technology parameters were determined. The ratio of the excipients and the best process parameters are established. Three batches of middle-scale products were manufactured under these process parameters. After determination of these bathes productions, we found that the process parameters were stable and the tablets were qualified.In accordance with the request of stability test of new veterinary drugs, the stability test mainly includes the influence factor experiment, acceleration test and long-term test. The result showed that arecoline hydrobromide were steady to high temperature, strong illumination but had deliquescence nature. The content was not obvious change when it and tablets were sealed and stored under 25±2℃and RH 60±5% for 12 months.The draft quality standards of arecoline hydrobromide and its tablets were instituted. U V (ultraviolet spectroscopy) was used to identify arecoline and RP-HPLC method was used for the determination of arecoline, the content limit was established. The results showed that the negative sample didn't interfere with the sample determination. Identification and content determination methods are stable, specific and repeatable. It can be used to control the quality of arecoline hydrobromide.The pharmacokinetics of arecoline hydrobromide tablets was arecoline hydrobromided initially. HPLC was used to establish the analysis method of arecoline in the plasma of dog. The result showed no effective concentration of arecoline was detected in plasma when the tablets were given to dog by 3mg/kg﹒bw through oral, this can be showed that the metabolism of arecoline was very quick or less of drugs were absorbed through the gastrointestinal tract.