Formulation, evaluation and optimization of orally disintegrating films of azithromycin using DOE approach for the pediatrics with acute otitis media

Acute otitis media (AOM) is a common infection of early childhood with an inflammation of the middle ear and tympanic membrane. Azithromycin is a macrolide antibiotic which is proficient to provide effective treatment for pediatric AOM due to its in-vitro activity against the most common upper respiratory tract pathogens. The objective of this study was to develop and optimize orally disintegrating films (ODF) of azithromycin as an alternative patient compliant dosage form. Using casting method of films, five formulations (F1-F5) were fabricated and evaluated for different physico-chemical and mechanical parameters along with drug release kinetics. Design of Experiment approach was applied to discover the optimized ratio of the two disintegrants used in the formulations. FT-IR spectra confirmed the identity of azithromycin and absence of any chemical interaction between the drug and excipients. Optimized formulation was selected as F2 which comprised of two disintegrants i.e. crospovidone and croscarmellose sodium in 1:1 ratio. F2 possessed excellent physico-chemical, mechanical properties along with rapid dissolution. F2 demonstrated concentration dependent erosional type release pattern from a planer surface of hydrophilic matrix system. Addition of the disintegrating agents resulted in rapid fragmentation of the films following the above process. Accelerated stability study assured the longer shelf life of optimized ODFs. Rapid disintegration and dissolution may accelerate the onset of action bypassing hepatic first-pass metabolism which confirmed the utility of azithromycin loaded ODFs as alternative dosage form in management of pediatric AOM.