Optimization and Evaluation of Thermosensitive Erythromycin in-situ Gel for Bullous Myringitis Using Central Composite Design
Akanksha Dwivedi, kuldeep Vinchurkar, Vaishali Sharma, Gajanan DarwhekarObjective:
The study aims to formulate and evaluate a thermosensitive in Situ gel of erythromycin for the treatment of bullous myringitis.
Methods:
A thermosensitive in situ gel of erythromycin was optimized for an ideal formulation, which was carried out using the ‘central composite’ design based on prime factors of the formulation, including sol-gel transition temperature, gelling time, in vitro % drug release, and viscosity, using “Design Expert” software and developed by dispersing variable concentrations of Poloxamer 407 and HPMC in distilled water, followed by addition of premixed drug solution in Isopropyl alcohol using constant stirring with a magnetic stirrer. Then, the formulations were stored overnight at 4°C to allow complete hydration of the polymer. All nine formulations were assessed for clarity, sol-gel transition temperature, gelling capacity, drug content, rheological studies, in vitro diffusion study, mucoadhesive strength, pH, ex vivo permeation, and antimicrobial efficacy against Streptococcus pneumoniae and Haemophilus influenzae.
Results:
All formulations demonstrated satisfactory physicochemical characteristics, including rapid gelling in 21-35 seconds and sol-gel transition temperatures between 32.3 and 42.3ºC. Viscosity tests verified that the substance was appropriate for both delivery and retention, and pH levels between 6.2 and 6.7 were in harmony with the environment of the ear canal. Prolonged residency was supported by mucoadhesive strength, and successful drug transport across the tympanic membrane was demonstrated by ex vivo permeation experiments. Significant inhibition zones against the investigated pathogens were shown by antimicrobial assessment. The best drug content (96.4%), sustained release (92.7±4.8% over 8 hours), high mucoadhesion, and excellent penetration properties were all displayed by ISG9 (19% poloxamer 407 and 1% HPMC).
Discussion:
The findings of the study suggest that the combination of poloxamer 407 and HPMC effectively produced a thermosensitive in situ gel, which exhibited a rapid sol-gel transition, prolonged retention, sustained drug release, and improved permeation. The optimized formulation (ISG9) also showed good antimicrobial activity, which indicates that it can improve localized treatment and reduce dosing frequency in bullous myringitis. Overall, the results support thermosensitive in situ gel as a promising approach for otic drug delivery. Still, further in vivo and clinical studies are needed to establish its therapeutic potential.
Conclusion:
The optimized thermosensitive in situ gel (ISG9) showed good gelation, mucoadhesion, sustained release, penetration, and antimicrobial activity, suggesting that it might be used as a novel otic drug delivery method to treat bullous myringitis.