Design, optimization, and evaluation for a long-time-released transdermal microneedle delivery system containing...

Area of Science:

• Pharmaceutical Sciences
• Biomaterials Engineering
• Drug Delivery Systems

Background:

• Transdermal drug delivery systems (TDDS) face challenges like poor absorption and low blood concentrations.
• Conventional microneedles (MNs) offer improved efficiency but struggle with mechanical strength and drug loading capacity.

Purpose of the Study:

• To develop and optimize a microemulsion-encapsulated, long-time-released transdermal microneedle (MN) system for estradiol (Es).
• To evaluate the enhanced transdermal efficiency, mechanical properties, and pharmacokinetic profile of the novel MN system.

Main Methods:

• Microemulsion (ME) optimization using pseudo-ternary phase diagram and D-optimal mixture design.
• Estradiol microemulsion-encapsulated microneedle (Es-ME-MN) optimization via Box-Behnken design and freeze-thaw preparation.
• Characterization of Es-ME-MN for mechanical strength, drug content, and in vitro/in vivo performance.

Main Results:

• Optimized Es-ME-MN exhibited sufficient mechanical strength (600 μm length) and high estradiol content (177.12 ± 0.72 μg/patch) without drug-excipient interaction.
• In vitro studies showed significantly higher transdermal efficiency and lower retention compared to commercial patches and conventional MNs.
• Pharmacokinetic studies demonstrated rapid achievement of effective blood concentrations (12.98-23.52 ng/mL) sustained for up to 72 hours.

Conclusions:

• The developed microemulsion-encapsulated, organic solvent-free transdermal microneedle system offers enhanced delivery of lipophilic drugs like estradiol.
• This novel MN system provides a promising new approach for improving transdermal drug delivery efficiency and duration.
• The system achieves rapid therapeutic blood levels and sustained release, addressing key limitations of existing TDDS.