A Novel Nanoemulsion Intermediate Gel as a Promising Approach for Delivery of Itraconazole: Design, In Vitro and Ex Vivo
- PDF / 1,162,995 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 16 Downloads / 203 Views
Research Article A Novel Nanoemulsion Intermediate Gel as a Promising Approach for Delivery of Itraconazole: Design, In Vitro and Ex Vivo Appraisal Sara R. Botros,1 Amal K. Hussein,2 and Heba F. Mansour2,3
Received 3 August 2020; accepted 22 September 2020 Abstract.
The aim the study was to design, formulate, and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) of itraconazole for improving the topical antifungal properties of the drug by adopting the nanoemulsion intermediate gel of the optimized system. Solubility study was conducted to select the most appropriate oils and surfactants for formulation. Different possible systems were created. Ternary phase diagrams were constructed to select the most promising system for further study. The nanoemulsion intermediate gel of the selected system was evaluated for stability, dilution effect, viscosity, pH, antifungal activity, droplet size, PDI, and zeta potential. In vitro release of the drug from the selected intermediate gel was investigated, and the kinetic model of drug release was determined. Ex vivo permeation of itraconazole was studied, and the amount of drug accumulated in the skin was calculated. Solubility and phase diagrams revealed that the system consisting of 60% cotton seed oil and 40% span 80 provided the nanoemulsion intermediate gel with the highest drug concentration. The selected system had a droplet size of about 236 nm and zeta potential of − 59.8. The viscosity of the corresponding intermediate gel was 1583.47 cp. The system exhibited high stability at 4°C and 25°C for 12 months and improved antifungal activity. In vitro release study showed complete release of itraconazole within 4 h, while the ex vivo permeation study revealed accumulation of the majority of the drug within the skin layers (72.5%).
KEY WORDS: nanoemulsion; intermediate gel; itraconazole; cotton seed oil.
INTRODUCTION Itraconazole (ITZ) is a potent triazole antimycotic agent (1), active against a broad spectrum of fungal species including Cryptococcus, Candida, Aspergillus, Blastomyces and Histoplasma (2), and Onychomycosis (1). Itraconazole is widely employed for the treatment of dermal and systemic fungal infections (3). The drug is a highly lipophilic weak base with a very low aqueous solubility (4), a logP of 5.66, and a pKa of 3.7 (2,3) which is ionized only at low pH. According to the Biopharmaceutics Classification System (BCS), itraconazole belongs to class II drugs. The drugs belonging to this class have too low water solubility to be Applied for Egyptian patent Electronic supplementary material The online version of this article (https://doi.org/10.1208/s12249-020-01830-w) contains supplementary material, which is available to authorized users. 1
Clinical Pharmacy Department, Faculty of Pharmacy, Minia University, Minia, Egypt. 2 Pharmaceutics Department, Faculty of Pharmacy, Minia University, P.O. Box: 61111, Minia, Egypt. 3 To whom correspondence should be addressed. (e–mail: [email protected])
consistent with complete absorption, despite thei
Data Loading...
