| Pridinol mesylate is a central anticholinergic drug, with useful muscle relaxant properties. The drug is most frequently used for muscle spasm and dyscinesia diseases (lumbago and back pain, neck-shoulder-wrist syndrome, omarthritis, spondylosis, et al) and Parkinson disease. Pridinol mesylate is just received by《The Japanese Pharmaceutical Codex (2002 Edition)》, not received by《Chinese Pharmacopoeia》. The only research that can be searched at home is the patent of "The orally disintegrating tablet of pridinol mesylate and the preparative method" (CN101664393) that applied by our team.The orally disintegrating tablet of pridinol mesylate is a national three class of new drugs. According to the State Food and Drug Administration Decree No.28 of "Drug Registration" in the "chemical registration requirements of the classification", the project studied the formula and preparation technique, standard of quality, general pharmacology and bioequivalence for the clinical trial and application of new drug.The research for formulation and preparation technique.The formulation was optimized with disintegration time and dissolution as reference parameters by an orthogonal design after single-factor experiment for disintegrants and correctants. The optimized prescription is:selected 4%PVPP as the disintegrant and the inside-outside proportion was 1:1,3% correctant which proportion of aspartame/steviosin was 6:1,15%MCC and 2% PVPK30, and the hardness is 15～20N. This formulation and preparation technique made the tablets integrity and smooth with desirable taste and feel in the mouth. The content and content uniformity were up to specification, the disintegration time was (21.85±2.3) s and the cumulative dissolution percentage was (98.01±0.83)% within 4 min.The research for quality standards. The study established a HPLC method for the detection of pridinol mesylate in orally disintegrating tablets and the method of dissolution. The chromatographic conditions:the mobile phase is consist of 0.05mol·L-1 sodium 1-octane sulfonate methanol-0.1% thophosphoric acid was 60:40(V/V), and the internal standard is butylparaben. The flow rate is 1.0mL/min and the determination wavelength was at 215nm. The column temperature is 30℃and the injection volume is 3μl. The results are reliable and accurate and this HPLC analysis method provided reference to estimate the quality of pridinol mesylate. Meanwhile, the research consist of characteristics, identification and examination of pridinol mesylate, the results were:white or off-white color rotundity tablet, sensitive identification, and the indexes of examination meet the requirements.General pharmacology. The study researched the effect of pridinol mesylate on the central nervous system, cardiovascular system and respiratory apparatus.The results, the orally disintegrating tablets showed no impact on general behavior and harmonious movement; there was no cooperativity with the hypnosis after giving pentobarbitale sodium at subthreshold dose; the freedom movement of mice grow downwards with high doseage of administration(1.316mg/kg), this could correlated with the sedation which created by action of anti-M1 muscarinic receptor of pridinol mesylate. This action showed shot time, disappeared after about 60min. And the drug did not affect the blood pressure, heart rate, electrocardiogram, respiratory rate of rats.Pharmacokinetics and bioavailability. The test compared the pharmacokinetic parameters and relative bioavailability between orallydisintegrating tablet and ordinary tablet of pridinol mesylate by the two preparations two cycles crossing trial design. HPLC determinated the blood drug level of pridinol mesylate in rabbits and treated the data by DAS2.0. The pharmacokinetic parameters:Orally disintegrating tablets:Cmax was (0.287±0.021) ug/mL, Tmax was (0.92±0.129) h and the AUC0-24h was (1.358±0.148) ug/mL*h; ordinary tablets:Cmax was (0.211±0.040) ug/mL, Tmax was (1.33±0.129) h and AUC0-24h was (1.272±0.187) ug/mL*h. The results indicates that the Cmax of orally disintegrating tablets was significantly higher than ordinary tablets (P＜0.05); the Tmax and AUC0-24h did not have significantly difference (P>0.05); and the relativebioavailability was 109.3%±23.8%. |
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