Technical challenges and quality considerations for dissolving microneedles

Area of Science:

• Pharmaceutical Sciences
• Biomaterials Engineering
• Drug Delivery Systems

Background:

• Dissolving microneedles (DMNs) offer transdermal drug delivery by penetrating the stratum corneum.
• Challenges exist in optimizing DMN formulations for mechanical properties and drug release.
• Lack of standardized quality control hinders DMN product development.

Purpose of the Study:

• To investigate testing methods for DMNs.
• To evaluate the impact of polymer-to-API ratio on DMN critical quality attributes (CQAs).
• To understand how CQAs influence drug release and skin permeation.

Main Methods:

• DMNs formulated with varying polyvinyl alcohol (PVA) concentrations and metoprolol succinate.
• Microscopic imaging with AI segmentation for morphological analysis.
• Intensity-distance analysis for drug distribution assessment.
• Mechanical testing (fracture force) and in vitro drug release/permeation studies.

Main Results:

• Pyramidal DMNs with consistent dimensions were successfully fabricated.
• Increased PVA content enhanced microneedle fracture force and structural integrity.
• Polymer-to-API ratio did not affect skin insertion or disintegration.
• Higher PVA content slowed drug release, identifying polymer as a key release controller.
• Drug permeation correlated with spatial drug distribution within the microneedles.

Conclusions:

• Optimizing the PVA-to-drug ratio is crucial for controlling DMN drug release and permeation.
• Controlling drug distribution within DMNs is essential for enhancing transdermal delivery performance.
• Standardized testing methods are needed to address quality control challenges in DMN development.