(T1230-03-14) Development of Soluble Microneedles Containing Ketoprofen with Improved Permeability and Bioavailability

Purpose: This study was to develop soluble microneedles containing ketoprofen as a new approach to improve skin permeability and bioavailability.

Methods: Appropriate polymers and surfactants for ketoprofen were selected based on solubility tests. The fabricated microneedles were poured into a 10 x10 PDMS mold (conical needles with a height of 1000 μm, a base width of 500 μm, a gap of 450 μm, and a patch area of 1 cm²) with tip solution and vacuum treated for 2 hours, and then the base solution (aqueous solution) was mixed with PVA-sucrose 1: 1 ratio) and leave to dry overnight. All microneedle preparations were visualized using a digital microscope. The polymer ratio was selected through mechanical property testing using a Texture Analyser. The in vitro release profile was studied in distilled water and PBS pH 7.4 by adding the surfactant poloxamer to selected polymer HPMC ratios, and skin penetration studies were performed using Franz diffusion cells in rat skin (PBS pH 7.4, 32°C). For in vivo pharmacokinetic studies, microneedles were inserted into the backs of SD rats, and drug concentrations in rat plasma were detected by HPLC.

Results: Ketoprofen-dissolving microneedles could form a homogeneous microneedle array (Figure 1A). 10% w/w HPMC showed the highest strength compared to other ratios of polymers in the fracture force evaluation (Figures 1C and 1D). In addition, 10% w/w HPMC was confirmed to have a hole creation rate of 100% due to a skin test on rat skin (Figure 1B). Release tests confirmed that the surfactant-loaded microneedles resulted in a 1.5-fold increase in release rate from distilled water, with faster 100% release at 1 hour in PBS pH7.4 (Figures 2A, 2B). In an in vitro Franz cell test, the concentration of surfactant-loaded microneedles increased from 36.5 ± 2.2 µg/cm2 to 72.0 ± 4.9 µg/cm² and 43.4 ± 4.4 µg/cm² in 24 hours, with an average cumulative amount of 500.4 ± 26.1 µg/cm² to 1000.3 ± 59.2 μg/cm², and 594.1 ± 52.6 μg/cm² (Figure 2C). It was confirmed that the bioavailability of ketoprofen also increased after applying the microneedle.

Conclusion: It was confirmed that soluble microneedles containing HPMC and poloxamer increase the drug permeability and bioavailability of ketoprofen.

References: Ramadon, Delly, et al. "Combination of dissolving microneedles with nanosuspension and Co-grinding for transdermal delivery of ketoprofen." Pharmaceuticals 16.3 (2023): 378.


Figure 1. (A) Digital image of Ketoprofen Dissolving Microneedle, (B) Digital image of Ketoprofen Dissolving Microneedle Skin test with 10% w/w HPMC, (C) Failure test for each HPMC ratio, (D) Insert test for each HPMC ratio.


Figure 2. (A) In vitro release test of distilled water. (B) In vitro release test of PBS pH7.4. (C) In vitro Franz cell test of PBS pH7.4.