氟雷拉纳咀嚼片原料与辅料相容性研究

Study on Compatibilities of Raw and Auxiliary Materials of Fluralaner Chewing Tablets

考察氟雷拉纳与各辅料的相容性,为氟雷拉纳咀嚼片处方设计提供依据,用影响因素试验对辅料进行筛选,将原料药氟雷拉纳与不同辅料按照一定比例混合,放在60℃、强光(4500±500)lx、相对湿度92.5%和75%条件下,在0 d和10 d分别考察原辅料混合样品的性状、含量及有关物质的变化。结果0 d时氟雷拉纳与明胶和泊洛沙姆188的混合样品中氟雷拉纳的含量低于95%,且与泊洛沙姆188混合样品中杂质增加。10 d时60℃高温条件下,氟雷拉纳与猪肝粉2号、交联羧甲基纤维素钠和丙二醇混合样品中的含量低于95%,杂质含量增加。其中氟雷拉纳与大豆油混合样品颜色发生轻微变化。在光照条件下,氟雷拉纳与各辅料混合样品中含量变化较小,杂质含量增加。在相对湿度92%条件下,氟雷拉纳与明胶、羧甲基纤维素钠、交联羧甲基纤维素钠、猪肝粉1号、猪肝粉2号、猪肝粉3号、泊洛沙姆188、丙二醇和甘油混合样品中含量低于95%,杂质含量增加且伴有性状变化。在相对湿度75%条件下,氟雷拉纳与猪肝粉3号、猪肝粉2号、明胶、羧甲基纤维素钠、交联羧甲基纤维素钠和丙二醇混合样品含量低于95%,杂质含量增加且伴有性状变化。而氟雷拉纳与聚乙二醇3350、玉米淀粉、羧甲基纤维素钠、甘油、猪肝粉1号、猪肝粉3号、大豆油、十二烷基硫酸钠、蔗糖、乳糖、甘露醇、山梨酸钾、苯甲酸钠、对羟基苯甲酸丙酯、硬脂酸镁、阿斯巴甜和微粉硅胶相容性好,可作为后续筛选的依据。

In order to investigate the compatibility of fluralaner with various excipients and provide a basis for the prescription design of fluralaner chewable tablets,the excipients were screened by the method of influencing factors test.After mixing the API fluralaner with different excipients in a certain proportion,Under high temperature 60℃,strong light(4500±500 lx),high humidity(RH 92.5%)and high humidity(RH 75%)conditions,and on 0 and 10 days respectively,the characteristics,content and related substance changes of raw and auxiliary materials mixed samples were investigated.The results showed that on 0 day,the content of fluralaner in the mixture of fluralaner with gelatin and Polosham 188 was lower than 95%,and the impurity in the mixture of fluralaner with Polosham 188 was increased.On 10 day,under the condition of 60℃,the content of the samples mixed with florellana and porcine liver powder No.2,crosslinked sodium carboxymethyl cellulose and propylene glycol was lower than 95%,the content of impurities increased,and the characteristics of the samples mixed with fluralaner and soybean oil showed a slight color change.Under the condition of illumination,the content of fluralaner mixed with excipients changed little and the content of impurities increased.Under the condition of high humidity(92%),the content of fluralaner mixed with gelatin,sodium carboxymethyl cellulose,sodium crosslinked carboxymethyl cellulose,porcine liver powder 1,porcine liver powder 2,porcine liver powder 3,Poloxam 188,propylene glycol and glycerol was less than 95%,and the content of impurities increased and the character changed.Under the condition of high humidity(75%),the content of fluralaner mixed with porcine liver powder 3,porcine liver powder 2,gelatin,sodium carboxymethyl cellulose,sodium crosslinked carboxymethyl cellulose and propylene glycol was lower than 95%,the content of impurities increased and the character changed.And the compatibilityies of fluralaner with polyethylene glycol(peg)3350,corn starch,sodium carboxymethyl cellulose,glycerin,porcine liver powder 1 and 3,soybean oil,sodium dodecyl sulfate,sucrose,lactose,mannitol,potassium sorbate,sodium benzoate,p-hydroxy benzoic acid propyl acetate,magnesium stearate,aspartame powder silica gel were good,can be used as a follow-up screening study basis.