Formulation And Evaluation Of Self-Emulsifying Drug Delivery Systems Of Azithromycin To Enhance Its Penetration Through The Epithelial Tight Junctions
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Date
2018-03
Authors
Assi, Reem Abou
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Azithromycin (AZM) is a macrolide antibiotic used for the treatment of a number of bacterial infections. It is known to have a low oral bioavailability (37 %) due to its relatively high molecular weight, incomplete solubility and/or poor intestinal permeability, which is potentially restricting its intestinal absorption. To overcome these drawbacks liquid and solid self-emulsifying drug delivery systems (L-SEDDs and S-SEDDs) of AZM were prepared in an attempt to enhance its solubility, and altering its cellular penetration, which might improve its oral bioavailability. Eight different pseudo-ternary diagrams were constructed based on AZM solubility and emulsification studies in different SEDDs excipients at different surfactant to co-surfactant (Smix) ratios. The selection criteria was droplet size (DS) < 150 nm, polydispersity index (PdI) ≤ 0.7, and transmittance (T) % > 85 in three diluents of distilled water (D.H2O), 0.1 mM HCl, and simulated intestinal fluids (SIF) as well as highest drug content. A final L-SEDDs formulation (F1(H)), which is composed of Capryol 90®, Tween 20®, and Transcutol HP® at the concentrations of 22.22 %, 51.85 %, and 25.93 % (v/v) respectively, was able to meet the selection criteria and had a DS of 141.57 ± 1.1 nm, PdI 0.52 ± 0.004, T% 90.1 ± 0.1, and drug content of 60.42 ± 0.4 mg/ml (p < 0.05). Accordingly, it was selected for conversion to S-SEDDs using different solidifying agents. Aerosil 200® produced S-SEDDs (FS-A200) with the smallest DS of 155.3 ± 1.91 nm, PdI 0.62 ± 0.03, and drug content of 38.79 ± 0.52 mg/g (p < 0.05). Blanks of F1(H) and FS-A200 formulations proved to be safe at different concentrations upon evaluating them in the microtiter tetrazolium (MTT) cytotoxicity assay.
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Keywords
Self-emulsifying drug delivery system , penetration through the epithelial tight junctions