Design, development, and characterization of posaconazole ethosomal in situ gel

Authors

Digambar Sawwashe
Rutuja Dattatray Chougale
Gitesh Gavande
Kiran Shivaji Patil
Shalaka Patki
John Disouza
Ashok Hajare

Abstract

Objective: This study aimed to develop an innovative ocular delivery system for posaconazole (PSC) using a gellan gum-based in situ ethosomal formulation, addressing the challenges posed by the poor solubility of PSC and the need for an effective treatment for fungal keratitis. Materials and Methods: Ethosomes were prepared using a thin-film hydration method with a mixture of ethanol, soya phosphatidylcholine, and cholesterol. A 3² factorial design was employed, with soya phosphatidylcholine (X₁) and cholesterol (X₂) concentrations as independent variables, and particle size (Y₁) and % entrapment efficiency (Y₂) as dependent variables. Compatibility studies using Fourier-transform infrared (FTIR) spectroscopy were conducted to assess potential drug-excipient interactions. Transmission electron microscopy (TEM) analysis was performed to evaluate the morphology of the developed ethosomes. In vitro drug release studies were carried out to investigate the permeation of PSC from plain and loaded ethosomes. Ex vivo studies using a goat cornea model were conducted to evaluate the corneal retention and permeation of the formulations. Results: The optimized F1 batch demonstrated a high % entrapment efficiency of 89.00±1.03% and smaller vesicles with a particle size of 239.4±1.21 nm. FTIR analysis confirmed the absence of drug-excipient interactions. TEM analysis revealed uniform spherical vesicles in the ethosomes. In vitro drug release studies demonstrated the sustained permeation of 81.23% of plain PSC and 51.50% of PSC-loaded ethosomes after 24 h. Ex vivo studies demonstrated the quick permeation of the developed in situ gel formulation in the goat cornea. Conclusion: The developed in-situ gel formulation loaded with PSC-loaded ethosomal vesicles offers a promising ocular delivery system for the effective treatment of deep fungal eye infections. The enhanced solubility, sustained drug release, and efficient corneal permeation of PSC make it a potential therapeutic option for fungal keratitis. Further, investigations and clinical studies are warranted to validate the efficacy and safety of this ocular delivery system.

DOI

10.56808/3027-7922.2840

Recommended Citation

Sawwashe, Digambar; Chougale, Rutuja Dattatray; Gavande, Gitesh; Patil, Kiran Shivaji; Patki, Shalaka; Disouza, John; and Hajare, Ashok (2023) "Design, development, and characterization of posaconazole ethosomal in situ gel," The Thai Journal of Pharmaceutical Sciences: Vol. 47: Iss. 4, Article 5.
DOI: https://doi.org/10.56808/3027-7922.2840
Available at: https://digital.car.chula.ac.th/tjps/vol47/iss4/5