左旋多巴咀嚼片的处方前研究

The pre-formulation study and preparation of L-dopa chewable tablets

目的对左旋多巴进行处方前研究,为设计优良的处方奠定基础。方法利用HPLC建立测定左旋多巴的体外分析方法学,并进行溶解度、油水分配系数、破坏性实验等处方前研究。结果采用HPLC建立了可靠的左旋多巴体外分析方法,在0.316～63mg·mL-1范围内线性良好(r=0.9999)。处方前研究证实左旋多巴易被氧化,不耐高温,在pH1.2的盐酸溶液中溶解度最大,在pH7.4的磷酸盐缓冲液和pH8.0的氢氧化钠碱性溶液中有降解,油水分配系数都小于0.5。结论建立的分析方法准确可靠。处方前研究表明左旋多巴遇光降解,在碱性溶液中不稳定,易被氧化,不耐高温。

Objective The preformulation properties of L-dopa are studied so as to design the premium formulation. Methods The HPLC method to determine the content of L-dopa was established. Based on the method, the saturate solubility in different pH media, the oil water partition coefficient （P） in different pH media and decomposition experiments on L-dopa were investigated. Results The HPLC method to determine the content of L-dopa is accurate and reliable for its good linearity （from 0. 316 mg · L^-1 to 63 mg · L^-1 ）（ r =0. 999 9）, intra- and inter-precision. The saturate solubility of L-dopa in hydrochloride solution of pH1. 2 was maximum, L-dopa was decomposed in phosphate buffer saline（PBS） of pHT. 4 and hydroxyl sodium solution of pH8. 0 and its oil water partition coefficients were all less than 0.5. Conclusion The HPLC method to determine the content of L-dopa is accurate and reliable. L-dopa is unstable in alkaline solution, oxidized easily, unstable under high temperature and light.