Joshi Prachi, Sangamwar Abhay T
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Mohali, Punjab, 160062, India.
Innovation and Development Centre (I&DC), Fresenius Kabi Oncology Ltd., Gurgaon, Haryana, 122001, India.
AAPS PharmSciTech. 2025 May 30;26(5):152. doi: 10.1208/s12249-025-03126-3.
Investigation on multidrug formulations is increasing, because of enhanced efficacy and patient compliance. The two antiparasitic drugs Albendazole (ABZ) and mebendazole (MBZ) combination is well reported in the clinical research. However, ABZ-MBZ drug combination do not progressed well due to in vivo drug-drug interaction of precipitation of either drug leading to sub-therapeutic concentration in systemic circulation. Herein, we studied the effect of various cellulosic polymers on the supersaturation behaviour of ABZ and MBZ in combination. We screened a large group of cellulosic polymers and selected HPMCAS on the basis of supersaturation behaviour, drug-polymer solubility, and drug particle size. An amorphous solid dispersion was developed comprising ABZ-MBZ and HPMCAS. Drug amorphization was confirmed using thermal and crystallographic technique. In kinetic solubility, the ternary ASD enhanced the solubility of ABZ/MBZ by 1.88/3.52-fold (pH 1.2), 146.08/201.38-fold (pH 6.8) and 182.47/50.38-fold (water) as compared to crystalline ABZ and MBZ. In vitro release study supports kinetic solubility data as in ternary ASD the fraction drug release of ABZ/MBZ was increased by 2.22/2.55-fold (pH 1.2), 22.82/25.98-fold (pH 6.8) and 18.5/12-fold (water) in comparison to crystalline drugs. AUC min displayed significant enhancement in drug solubility with ternary ASD.
由于疗效增强和患者依从性提高，对多药制剂的研究正在增加。两种抗寄生虫药物阿苯达唑（ABZ）和甲苯达唑（MBZ）的组合在临床研究中有充分报道。然而，由于两种药物沉淀的体内药物相互作用导致全身循环中的亚治疗浓度，ABZ-MBZ药物组合进展不佳。在此，我们研究了各种纤维素聚合物对ABZ和MBZ组合的过饱和行为的影响。我们筛选了一大组纤维素聚合物，并根据过饱和行为、药物-聚合物溶解度和药物粒径选择了醋酸羟丙甲纤维素琥珀酸酯（HPMCAS）。开发了一种包含ABZ-MBZ和HPMCAS的无定形固体分散体。使用热学和晶体学技术确认了药物非晶化。在动力学溶解度方面，与结晶态的ABZ和MBZ相比，三元无定形固体分散体在pH 1.2时将ABZ/MBZ的溶解度提高了1.88/3.52倍，在pH 6.8时提高了146.08/201.38倍，在水中提高了182.47/50.38倍。体外释放研究支持动力学溶解度数据，因为与结晶药物相比，在三元无定形固体分散体中，ABZ/MBZ的药物释放分数在pH 1.2时增加了2.22/2.55倍，在pH 6.8时增加了22.82/25.98倍，在水中增加了18.5/12倍。三元无定形固体分散体的AUCmin显示药物溶解度有显著提高。
