MODIFIED CYCLODEXTRIN-BASED THERMOSENSITIVE IN SITU GEL FOR VORICONAZOLE OCULAR DELIVERY AGAINST FUNGAL KERATITIS

SUNITHA SAMPATHI; SRAVYA MADDUKURI; RAMDAS RAMAVATH; SUJATHA DODOALA; VIJAYA KUCHANA

doi:10.22159/ijap.2024v16i1.48817

Authors

SUNITHA SAMPATHI Department of Pharmacy, School of Pharmacy, Vishwakarma University, Pune-411048, Maharashtra, India
SRAVYA MADDUKURI GITAM School of Pharmacy, GITAM Deemed to be University, Hyderabad-502329, India https://orcid.org/0000-0003-3887-9770
RAMDAS RAMAVATH Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Balanagar, Hyderabad-500037, India
SUJATHA DODOALA Institute of Pharmaceutical Technology, Sri Padmavathi Mahila Visvavidyalayam-517502, Tirupati, Andhra Pradesh, India
VIJAYA KUCHANA TKR College of Pharmacy, Meerpet, Hyderabad, Telangana 500097, India

DOI:

https://doi.org/10.22159/ijap.2024v16i1.48817

Keywords:

T. coronaria, Anti-acne emulgels, In vivo studies, Anti-bacterial effect

Abstract

Objective: Fungal keratitis is a severe corneal infection. The present study aims to design and formulate an inclusion complex of Voriconazole-Sulfobutyl ether-beta-cyclodextrin (V-SBECD) loaded thermosensitive in-situ gel to improve solubility, therapy efficacy, durability and reduce the dose-related side effect.

Methods: Poloxamer 407, a thermosensitive polymer along with hydroxypropyl methylcellulose (HPMC E 15), were used as gelling agents; the formulations with poloxamer (16% w/v) and HPMC E15 (1 and 1.5 % w/v) led to a consistent in-situ gel at 37 °C. The formulations were evaluated for drug content, pH, gelation temperature, viscosity, sterility test, antifungal studies, and cell lines studies.

Results: The molar ratio of the drug to SBECD (1:3), showing 42-fold increase in solubility, was chosen to prepare the inclusion complexes using the lyophilization method. The stability constant was found to be 721^-m.ATIR peaks, DSC thermograms and NMR spectra indicate the inclusion behavior of Voriconazole and SBECD. In vitro and ex-vivo studies demonstrated that optimized formulation sustained the drug release for over 12 h. Cellular cytotoxicity on Human corneal epithelial cells showed that V-SBECD formulations do not cause corneal epithelial damage after 24 h. In-situ gel and marketed formulation have shown a markable reduction in the growth of the Aspergillus Niger. The optimized SBECD-loaded in-situ gel formulation (F10) did not vary significantly in pH, drug content, viscosity, and % cumulative drug release, signifying stable formulations when tested at 4, 25, and 40 °C.

Conclusion: The research findings envisaged V-SBECD in-situ gel formulation as a concrete strategy to treat severe fungal keratitis.

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