FORMULATION STRATEGY FOR STABLE POSACONAZOLE NANOEMULSION: APPLICATION OF PSEUDOTERNARY PHASE DIAGRAM IN PREFORMULATION DESIGN

MOHAMMED SADIK HAMZA; ZAINAB THABIT SALEH

doi:10.22159/ijap.2025v17i5.55055

Authors

MOHAMMED SADIK HAMZA University of Babylon, College of Pharmacy, Department of Pharmaceutics, Babylon, Iraq https://orcid.org/0009-0004-0913-3253
ZAINAB THABIT SALEH University of Baghdad, College of Pharmacy, Department of Pharmaceutics, Baghdad, Iraq https://orcid.org/0000-0002-3672-6706

DOI:

https://doi.org/10.22159/ijap.2025v17i5.55055

Keywords:

Posaconazole, Nanoemulsion, Pseudo-ternary phase diagram, Droplet size

Abstract

Objective: posaconazole (PCZ), a potent broad-spectrum antifungal agent of the triazole class, is categorized as a Biopharmaceutical Classification System (BCS) Class II drug due to its poor aqueous solubility and limited oral bioavailability. Conventional PCZ formulations exhibit compromised therapeutic efficacy. This study aimed to develop and characterize an intravaginal nanoemulsion (NE) system as a novel drug delivery system (NDDS) to enhance PCZ solubility, avoid hepatic first-pass metabolism, and ensure rapid and complete drug release.

Methods: A systematic solubility screening of PCZ was conducted using various oils, surfactants, and co-surfactants. Pseudoternary phase diagrams were constructed to identify optimal NE regions. Based on these diagrams, multiple formulations were prepared and evaluated via visual inspection, thermodynamic stability, light transmittance, pH measurement, drug content, dilution test, and droplet size analysis.

Results: Among the tested formulations, F5 was optimized, demonstrating superior physicochemical characteristics. It showed the highest drug content (99.87%±0.20), a droplet size of (102.9±0.12 nm), a polydispersity index (0.28±0.008), and a zeta potential of (-29.45±0.09 mV). In vitro drug release revealed complete PCZ release (100%) within 150 min in citrate phosphate buffer (pH 4.5) with 1% Tween 80.

Conclusion: The optimized NE (F5), composed of 30% Imwitor 988, 30% S-mix (Tween 20: Transcutol, 1:1), 40% distilled water, and 1% PCZ, demonstrated excellent stability and a rapid drug release profile. Compared to clotrimazole-based vaginal tablets, which exhibit slower and incomplete drug release, this nanoemulsion offers enhanced solubility, efficient local delivery, and bypasses hepatic metabolism, making it a promising candidate for vaginal PCZ administration.

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