Quality by design-enabled development and characterisation of nanocarrier of azithromycin

Background: Azithromycin is an antibiotic, which is preferentially used in the treatment of Mycobacterium Avium Complex (MAC). However, it suffers from drawbacks such as poor solubility, poor bioavailability and adverse effects such as gastrointestinal intolerance, resulting into poor patient compliance. Aim: To develop and optimize lipid based nanocarriers of Azithromycin using QbD approach. Methods: Nanostructured lipid carrier (NLC) were developed by using the solvent diffusion evaporation method with view to release drug in a sustained release manner. The initial factors screening and risk assessment done through Taguchi design and afterwards the optimization of independent factors along with final outcome i.e. critical quality attributes (CQAs) were done by Box Behnken Design (BBD). Results: The results of Physicochemical analysis revealed that a size of optimized Azithromycin Nanocarrier is 346.18 ± 12.90 nm and Polydispersity Index (PDI) of 0.21 ± 0.08; the entrapment efficiency (% EE) of 68.45 ± 4.42% w/w and drug loading of 47.16 ± 0.80 % w/w. The in vitro release study of the Azithromycin Nanocarrier showed a biphasic drug release pattern in simulated intestinal fluid (SIF) nanocarrier shown sustained release kinetics up to 02 days and similar pattern shown in Phosphate buffer saline (PBS) pH 7.4, release kinetics shows initial burst release upto 12 hr followed by sustained release upto 04 days in PBS, pH7.4. The sustained release pattern of the formulation is beneficial to improve the oral bioavailability of the drug. Conclusion: Thus, present research leads to development of formulations which may reduce dose of drug, dosing frequency and enhanced efficaciously of drug. Ultimately it reducing the patient avoidance in treatment.