正交设计优化盐酸氨溴索口腔崩解片的处方

Optimization of Formulation of Ambroxol Hydrochloride Orally Disintegrating Tablets by Orthogonal Test

目的:对盐酸氨溴索口腔崩解片的处方进行优化。方法:参照市售盐酸氨溴索片中主药含量,确定盐酸氨溴索口腔崩解片中主药用量;选用枸橼酸、酒石酸和富马酸3种矫味酸,两两组合,与微晶纤维素和甘露醇一并进行正交试验,以志愿者对苦味、麻和涩等的口感以及崩解时限、溶出度等为指标,确定微晶纤维素和甘露醇的用量以及矫味酸的种类和用量;将阿司帕坦、薄荷粉末香精和苹果粉末香精分别作为甜味剂和矫味剂,根据志愿者服用后的口感评分,确定其用量;以休止角为指标,确定助流剂硬脂酸镁的用量;交联羧甲基纤维素钠采用常规用量,即占处方的3%。结果:优化处方为:每1000片含盐酸氨溴索30g,甘露醇20g,微晶纤维素40g,枸橼酸10g,富马酸10g,阿司帕坦5g,薄荷粉末香精0.5g,苹果粉末香精0.5g,硬脂酸镁1g,交联羧甲基纤维素钠4g。采用优化处方制备的盐酸氨溴索口腔崩解片口感明显改善,崩解时限和溶出度均符合要求,并与市售盐酸氨溴索片生物等效,起效更迅速。结论:得到了符合盐酸氨溴索口腔崩解片剂型要求的处方。

Objective： To optimize the formulation of ambroxol hydrochloride orally disintegrating tablets. Methods： The quantity of ambroxol hydrochloride was determined with reference to the content of arnbroxol hydrochloride tablets sold on market. The quantities of mannitol, microcrystalline cellulose, as well as the kinds and quantities of the taste-modifying acids were optimized by orthogonal test in which people used taste, disintegration time and dissolution as evaluation indexes. The quantity of aspartame, peppermint powder flavor and apple powder flavor were determined according to the scores for the taste from the volunteers. The quantity of magnesium stearate was determined by using powder＇s angle of repose as indexes, and the quantity of croscarmellose sodium was determined by adopting the conventional ratio （3%） in formulationResults： The best formulation was as follows： ambroxol hydroehloride 30 g,microerystalline cellulose 40 g, citric acid 10 g, fumarie acid 10 g, aspartame 5 g, peppermint powder flavor 0.5 g, apple powder flavor 0.5 g, magnesium stearate 1 g, and croscarmellose sodium 4 g every 1 000 tablets. The taste of ambroxol hydrochloride orally disintegrating tablets prepared by using the optimized formulation were improved obviously, the disintegration time and dissolution also meet requirements, and it was biologically equivalent to ambroxol hydrochloride tablets sold on market, especially showing more rapid drug releasing. Conclusion： An optimized formulation of ambroxol hydrochloride orally disintegrating tablets which meets the requirements of the design was obtained.