五氯柳胺阿苯达唑复方混悬液辅料相容性研究
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摘要
为了考察五氯柳胺、阿苯达唑与不同辅料的相容性,为复方混悬液处方设计提供依据,采用影响因素试验方法对辅料进行筛选,将原料药五氯柳胺、阿苯达唑和不同辅料按照一定的比例混合后存放于高温(60℃)和强光(4500±500)Lx条件下,并于第0天和第10天考察原辅料混合样品的性状、含量及有关物质的变化。结果显示:第0天时,五氯柳胺、阿苯达唑与硅酸铝镁、海藻酸钠、焦亚硫酸钠的混合样品溶液中阿苯达唑含量低于95%,且杂质含量也增加。第10天时,60℃高温条件下,五氯柳胺、阿苯达唑与卡波姆、十二烷基硫酸钠、吐温-20、维生素E、焦亚硫酸钠、抗坏血酸棕榈酸酯、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、山梨酸钾的样品溶液中阿苯达唑含量低于95%,杂质含量增加且伴有性状变化;(4500±500)Lx光照条件下,抗坏血酸棕榈酸酯样品溶液中五氯柳胺含量大于105%,山梨酸钾样品溶液中五氯柳胺含量低于95%,杂质含量增加且伴有性状变化。而五氯柳胺、阿苯达唑与辅料羧甲基纤维素钠、聚乙烯吡咯烷酮、黄原胶、黄蓍树胶、大豆油、甘油、吐温-80、二甲基硅油、柠檬酸、柠檬酸钠、磷酸氢二钠、苯甲酸、苯甲酸钠相容性好,可作为后续处方筛选研究依据。
This study was on the compatibility of oxyclozanide and albendazole with different excipients in order to provide references for formulation design of compound suspension. The influence factor experiments were performed to screen excipients. Raw materials, oxyclozanide and albendazole and different excipients were blended by a certain proportion and were then stored at high temperature(60 ℃) and under strong illumination(4500±500) Lx conditions. The changes in the mixtures including their traits, content and related substances were observed and analyzed at the 0~(th) and 10~(th) days. The results showed that the content of albendazole was less than 95% when blended with the excipients, aluminum magnesium silicate, sodium alginate and sodium metabisulfite, and the content of impurities was increased at 0~(th) day. At the 10~(th) day, the content of albendazole was less than 95% under high temperature condition when mixed with the excipients, carbomer, sodium dodecyl sulfate, tween-20, vitamin E, sodium pyrosulfite, ascorbic acid palmitat, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, and potassium sorbate; and the traits of mixtures varied with the increasing impurities. Under the condition of strong illumination of 4500 Lx, the content of oxyclozanide in the ascorbic acid palmitate solution was more than 105%, but the content of oxyclozanide in potassium sorbate solution was less than 95%; and variation of the traits with an increase of impurities occurred at both occastions. To sum up, a good compatibility was observed of raw materials and excipients, sodium carboxymethyl cellulose, polyvinylpyrrolidone, xanthan gum, tragacanth gum, soybean oil, glycerin, tween-80, dimethyl silicone oil, citric acid, sodium citrate, sodium phosphate dibasic, benzoic acid and sodium benzoic, which laid the basis for future research on prescription screening.
This study was on the compatibility of oxyclozanide and albendazole with different excipients in order to provide references for formulation design of compound suspension. The influence factor experiments were performed to screen excipients. Raw materials, oxyclozanide and albendazole and different excipients were blended by a certain proportion and were then stored at high temperature(60 ℃) and under strong illumination(4500±500) Lx conditions. The changes in the mixtures including their traits, content and related substances were observed and analyzed at the 0~(th) and 10~(th) days. The results showed that the content of albendazole was less than 95% when blended with the excipients, aluminum magnesium silicate, sodium alginate and sodium metabisulfite, and the content of impurities was increased at 0~(th) day. At the 10~(th) day, the content of albendazole was less than 95% under high temperature condition when mixed with the excipients, carbomer, sodium dodecyl sulfate, tween-20, vitamin E, sodium pyrosulfite, ascorbic acid palmitat, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, and potassium sorbate; and the traits of mixtures varied with the increasing impurities. Under the condition of strong illumination of 4500 Lx, the content of oxyclozanide in the ascorbic acid palmitate solution was more than 105%, but the content of oxyclozanide in potassium sorbate solution was less than 95%; and variation of the traits with an increase of impurities occurred at both occastions. To sum up, a good compatibility was observed of raw materials and excipients, sodium carboxymethyl cellulose, polyvinylpyrrolidone, xanthan gum, tragacanth gum, soybean oil, glycerin, tween-80, dimethyl silicone oil, citric acid, sodium citrate, sodium phosphate dibasic, benzoic acid and sodium benzoic, which laid the basis for future research on prescription screening.
引文
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[11] Mcginity J W,Lach J L.In vitro adsorption of various pharmaceutical to montmorillonite[J].J Pharm Sci,1976,65(6):896-902.
[12] Sukhorukov G B,Volodkin D V,Günther A M,et al.Porous calcium carbonate microparticles as templates for encapsulation of bioactive compounds[J].J Material Chem,2004,14(14):2073-2081.
[13] Schumacher G E,Hull R L.Some factors influencing the degradation of sodium bisulfite in dextrose solutions[J].Am J Hosp Pharm,1966,23(5):245-249.
[14] Patel N K,Kostenbauder H B.Interaction of preservatives with macromolecules I.binding of parahydroxybenzoic acid esters by polyoxyethylene 20 sorbitan monooleate(tween 80)[J].J Am Pharm Assoc Am Pharm Assoc,1958,47(4):289-293.
[15] Alade S L,Brown R E,Jr P A.Polysorbate 80 and E-Ferol toxicity[J].Pediatrics,1986,77(4):593-597.
[16] Balistreri W F,Farrell M K,Bove K E.Lessons from the E-Ferol tragedy[J].Pediatrics,1986,78(3):503-506.
[17] Allwood M C.Compatibility and stability of TPN mixtures in big bags[J].J Clin Hosp Pmi,1984,9(3):181-198.
[18] Tai A,Takebayashi J,Ueno A,et al.An isocratic HPLC method for the simultaneous determination of novel stable lipophilic ascorbic acid derivatives and their metabolites[J].J Chromatogr B Analyt Technol Biomed Life Sci,2006,840(1):38-43.
[19] Amirpour M,Arman A,Yolmeh A,et al.Sodium benzoate and potassium sorbate preservatives in food stuffs in Iran[J].Food Addit Contam Part B Surveill,2015,8(2):142-148.
[2] Palmeirim M S,Hürlimann E,Knopp S,et al.Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths:a systematic review meta-analysis and individual patient data analysis[J].PLoS Negl Trop Dis,2018,12(4):e0006458.
[3] Veenendaal G H,Waal M J.Uncoupling activity of the anthelmintic oxyclozanide in rodents[J].Br J Pharmacol,1974,50(3):435-437.
[4] Sanabria R,Moreno L,Alvarez L,et al.Efficacy of oxyclozanide against adult paramphistomum leydeni in naturally infected sheep[J].Vet Parasitol,2014,206(3-4):277-281.
[5] Markoski M M,Trindade E S,Cabrera G,et al.Praziquantel and albendazole damaging action on in vitro developing Mesocestoides corti(Platyhelminthes:Cestoda)[J].Parasitol Int,2006,55(1):51-61.
[6] Salinas J L,Vildozola G H,Astuvilca J,et al.Long-term albendazole effectiveness for hepatic cystic echinococcosis[J].Am J Trop Med Hyg,2011,85(6):1075-1079.
[7] Sawant K K,Patel M H,Patel K.Cefdinir nanosuspension for improved oral bioavailability by media milling technique:formulation,characterization and in vitro-in vivo evaluations[J].Drug Dev Ind Pharm,2015,42(5):758-768.
[8] 农业部兽药评审中心.兽药研究技术指导原则汇编[M].北京:化学工业出版社,2012.
[9] Abou-taleb A E,Abdel-rahman A A,Samy E M,et al.Formula-tion and evaluation of rofecoxib capsules[J].Saudi Pharm J,2009,17(1):40-50.
[10] 党丽梅.阿苯达唑混悬剂的制备及其质量控制[D].咸阳:西北农林科技大学,2015.
[11] Mcginity J W,Lach J L.In vitro adsorption of various pharmaceutical to montmorillonite[J].J Pharm Sci,1976,65(6):896-902.
[12] Sukhorukov G B,Volodkin D V,Günther A M,et al.Porous calcium carbonate microparticles as templates for encapsulation of bioactive compounds[J].J Material Chem,2004,14(14):2073-2081.
[13] Schumacher G E,Hull R L.Some factors influencing the degradation of sodium bisulfite in dextrose solutions[J].Am J Hosp Pharm,1966,23(5):245-249.
[14] Patel N K,Kostenbauder H B.Interaction of preservatives with macromolecules I.binding of parahydroxybenzoic acid esters by polyoxyethylene 20 sorbitan monooleate(tween 80)[J].J Am Pharm Assoc Am Pharm Assoc,1958,47(4):289-293.
[15] Alade S L,Brown R E,Jr P A.Polysorbate 80 and E-Ferol toxicity[J].Pediatrics,1986,77(4):593-597.
[16] Balistreri W F,Farrell M K,Bove K E.Lessons from the E-Ferol tragedy[J].Pediatrics,1986,78(3):503-506.
[17] Allwood M C.Compatibility and stability of TPN mixtures in big bags[J].J Clin Hosp Pmi,1984,9(3):181-198.
[18] Tai A,Takebayashi J,Ueno A,et al.An isocratic HPLC method for the simultaneous determination of novel stable lipophilic ascorbic acid derivatives and their metabolites[J].J Chromatogr B Analyt Technol Biomed Life Sci,2006,840(1):38-43.
[19] Amirpour M,Arman A,Yolmeh A,et al.Sodium benzoate and potassium sorbate preservatives in food stuffs in Iran[J].Food Addit Contam Part B Surveill,2015,8(2):142-148.