Aucamp Marique, Odendaal Roelf, Liebenberg Wilna, Hamman Josias
Center of Excellence for Pharmaceutical Sciences, North-West University , Potchefstroom , South Africa.
Drug Dev Ind Pharm. 2015;41(7):1100-8. doi: 10.3109/03639045.2014.931967. Epub 2014 Jul 1.
Azithromycin (AZM) is a poorly soluble macrolide antibacterial agent. Its low solubility is considered as the major contributing factor to its relatively low oral bioavailability. The aim of this study was to improve the solubility of this active pharmaceutical ingredient (API) by preparing an amorphous form by quench cooling of the melt and to study the influence of the improved solubility on membrane permeability. The amorphous azithromycin (AZM-A) exhibited a significant increase in water solubility when compared to the crystalline azithromycin dihydrate (AZM-DH). The influence that the improved solubility could have on membrane permeability was also studied. The apparent permeability coefficient (Papp) values of AZM-A were statistically significantly higher (p < 0.05) than crystalline AZM-DH at pH values of 6.8 and 7.2. The results therefore indicated that the improved solubility of AZM in the amorphous form also produced improved permeability across excised intestinal tissue at physiological pH values found in the small intestine.
阿奇霉素（AZM）是一种难溶性大环内酯类抗菌剂。其低溶解度被认为是导致其口服生物利用度相对较低的主要因素。本研究的目的是通过对熔体进行骤冷冷却来制备无定形形式，以提高这种活性药物成分（API）的溶解度，并研究溶解度提高对膜通透性的影响。与结晶二水合阿奇霉素（AZM-DH）相比，无定形阿奇霉素（AZM-A）的水溶性显著增加。还研究了溶解度提高对膜通透性可能产生的影响。在pH值为6.8和7.2时，AZM-A的表观渗透系数（Papp）值在统计学上显著高于结晶AZM-DH（p < 0.05）。因此，结果表明，无定形形式的AZM溶解度提高，在小肠中发现的生理pH值下，其对离体肠组织的通透性也有所提高。
