Abstract
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 (Đ) ≤ 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(H)), and S-SEDDs (S-F1(H)) 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.
Highlights
Oral drug delivery is the most widely used and the common route of drug administration because it is convenient, economical, comfortable, and requires no special training for use [1,2]
Many reports are suggesting that it might be attributed to different factors such as the low aqueous solubility (AZM is practically insoluble in water) which may lead to erratic dissolution rates [11,12,13,14,15], the drug relatively high molecular weight, the low stability at the acidic gastric pH (AZM have a high potential of decomposition in acidic medium) [16], and the incomplete gastrointestinal tract (GIT) absorption [17]
Some reports are suggesting that AZM may increase the transepithelial electrical resistance (TEER) values when studied in certain cell lines such as human airway epithelial cell lines [21,22], which could be linked to changing the processing of tight junction proteins [22,23]
Summary
Oral drug delivery is the most widely used and the common route of drug administration because it is convenient, economical, comfortable, and requires no special training for use [1,2]. The drug, which is included in the model list of essential medicines on the World Health Organization website [7], is classified as the first azalide subclass among its family members [8,9] with a superior antibacterial activity in the market for the last three decades This makes AZM the drug of choice for the treatment of various gastrointestinal, respiratory, and genitourinary infections. Some reports are suggesting that AZM may increase the transepithelial electrical resistance (TEER) values when studied in certain cell lines such as human airway epithelial cell lines [21,22], which could be linked to changing the processing of tight junction proteins [22,23] This may lead to a negative impact on AZM paracellular transport and permeability. The only other available dosage form of AZM is the intravenous infusion, which is associated with severe adverse effects, including pain at the injection site and local inflammation [24]
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