Addressing Solubility and Analytical Challenges in Transdermal Nystatin Microneedle Formulation

Additional Authors

Caleb Miller, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN Zachary Kennedy, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN

Abstract

Fungal infections, particularly those caused by Candida albicans, present a significant therapeutic challenge due to the need for frequent topical applications of antifungal agents like nystatin. Microneedles (MNs) offer a novel transdermal delivery system that could enhance therapeutic efficacy by enabling controlled and sustained drug release. This study focuses on the preformulation aspects of nystatin MNs, including solubility enhancement, analytical method development, and drug release evaluation. Nystatin MNs were fabricated using MeltPrep vacuum compression molding (VCM), a novel technique that employs heat and vacuum for precise formulation. To enable in vitro skin permeation studies via Franz Diffusion Cells, an HPLC-based analytical method was developed to detect nystatin with high sensitivity while avoiding interference from skin components. Given nystatin’s poor water solubility, various solubility enhancers were screened using citrate-phosphate buffer (CPB) combined with polyethylene glycol (PEG 400) or Transcutol at varying ratios. Solubility studies involved saturation and centrifugation steps, followed by HPLC analysis of the supernatant. The optimized HPLC method achieved a detection sensitivity of 0.1 µg/mL, with a linearity range of 0.1–50 µg/mL (R² = 0.9958). The mobile phase consisted of methanol:DMF:water (55:15:30) with a C18 column, a flow rate of 0.8 mL/min, and a retention time of ~7.5 min. Among the tested solubility enhancers, CPB:Transcutol (1:1) provided the highest solubility (290.44 ± 12.10 µg/mL) and was selected as the receptor medium for skin permeation studies. MN drug release studies demonstrated complete dissolution of 2 mg nystatin within 2 hours in CPB:Transcutol (1:1). This study successfully optimized solubility conditions and established a robust HPLC method for nystatin quantification in MN formulations. Future work will investigate transdermal permeation across pig ear skin using Franz cells to evaluate MN-mediated nystatin delivery.

Start Time

16-4-2025 1:30 PM

End Time

16-4-2025 4:00 PM

Presentation Type

Poster

Presentation Category

Health

Student Type

Clinical Doctoral Student (e.g., medical student, pharmacy student)

Faculty Mentor

Ashana Puri

Faculty Department

Pharmaceutical Sciences

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Apr 16th, 1:30 PM Apr 16th, 4:00 PM

Addressing Solubility and Analytical Challenges in Transdermal Nystatin Microneedle Formulation

Fungal infections, particularly those caused by Candida albicans, present a significant therapeutic challenge due to the need for frequent topical applications of antifungal agents like nystatin. Microneedles (MNs) offer a novel transdermal delivery system that could enhance therapeutic efficacy by enabling controlled and sustained drug release. This study focuses on the preformulation aspects of nystatin MNs, including solubility enhancement, analytical method development, and drug release evaluation. Nystatin MNs were fabricated using MeltPrep vacuum compression molding (VCM), a novel technique that employs heat and vacuum for precise formulation. To enable in vitro skin permeation studies via Franz Diffusion Cells, an HPLC-based analytical method was developed to detect nystatin with high sensitivity while avoiding interference from skin components. Given nystatin’s poor water solubility, various solubility enhancers were screened using citrate-phosphate buffer (CPB) combined with polyethylene glycol (PEG 400) or Transcutol at varying ratios. Solubility studies involved saturation and centrifugation steps, followed by HPLC analysis of the supernatant. The optimized HPLC method achieved a detection sensitivity of 0.1 µg/mL, with a linearity range of 0.1–50 µg/mL (R² = 0.9958). The mobile phase consisted of methanol:DMF:water (55:15:30) with a C18 column, a flow rate of 0.8 mL/min, and a retention time of ~7.5 min. Among the tested solubility enhancers, CPB:Transcutol (1:1) provided the highest solubility (290.44 ± 12.10 µg/mL) and was selected as the receptor medium for skin permeation studies. MN drug release studies demonstrated complete dissolution of 2 mg nystatin within 2 hours in CPB:Transcutol (1:1). This study successfully optimized solubility conditions and established a robust HPLC method for nystatin quantification in MN formulations. Future work will investigate transdermal permeation across pig ear skin using Franz cells to evaluate MN-mediated nystatin delivery.