Abou Assi Reem, M Abdulbaqi Ibrahim, Seok Ming Toh, Siok Yee Chan, A Wahab Habibah, Asif Shaik Mohammed, Darwis Yusrida
The Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
The Discipline of Pharmaceutical Technology, College of Pharmacy, Al-Kitab University, Altun kupri, Kirkuk 36001, Iraq.
Pharmaceutics. 2020 Nov 4;12(11):1052. doi: 10.3390/pharmaceutics12111052.
Azithromycin (AZM) is a macrolide antibiotic used for the treatment of various bacterial infections. The drug is known to have low oral bioavailability (37%) which may be attributed to its relatively high molecular weight, low solubility, dissolution rate, and incomplete intestinal absorption. To overcome these drawbacks, liquid (L) and solid (S) self-emulsifying drug delivery systems (SEDDs) of AZM were developed and optimized. Eight different pseudo-ternary diagrams were constructed based on the drug solubility and the emulsification studies in various SEDDs excipients at different surfactant to co-surfactant (Smix) ratios. Droplet size (DS) < 150 nm, dispersity () ≤ 0.7, and transmittance (T)% > 85 in three diluents of distilled water (DW), 0.1 mM HCl, and simulated intestinal fluids (SIF) were considered as the selection criteria. The final formulations of L-SEDDs (L-F1), and S-SEDDs (S-F1) were able to meet the selection requirements. Both formulations were proven to be cytocompatible and able to open up the cellular epithelial tight junctions (TJ). The drug dissolution studies showed that after 5 min > 90% and 52.22% of the AZM was released from liquid and solid SEDDs formulations in DW, respectively, compared to 11.27% of the pure AZM, suggesting the developed SEDDs may enhance the oral delivery of the drug. The formulations were stable at refrigerator storage conditions.
阿奇霉素（AZM）是一种用于治疗各种细菌感染的大环内酯类抗生素。已知该药物口服生物利用度较低（37%），这可能归因于其相对较高的分子量、低溶解度、溶解速率以及不完全的肠道吸收。为克服这些缺点，研发并优化了阿奇霉素的液体（L）和固体（S）自乳化药物递送系统（SEDDs）。基于药物溶解度以及在不同表面活性剂与助表面活性剂（Smix）比例下各种SEDDs辅料中的乳化研究，构建了八个不同的伪三元相图。在蒸馏水（DW）、0.1 mM盐酸和模拟肠液（SIF）三种稀释剂中，液滴尺寸（DS）< 150 nm、分散度（）≤ 0.7以及透光率（T）% > 85被视为选择标准。液体SEDDs（L-F1）和固体SEDDs（S-F1）的最终制剂能够满足选择要求。两种制剂均被证明具有细胞相容性，并且能够打开细胞上皮紧密连接（TJ）。药物溶出度研究表明，5分钟后，阿奇霉素在DW中分别从液体和固体SEDDs制剂中释放出> 90%和52.22%，相比之下纯阿奇霉素的释放率为11.27%，这表明所研发的SEDDs可能会提高药物的口服递送效果。这些制剂在冰箱储存条件下是稳定的。
