Dissolving Microneedle Formulation of Ceftriaxone: Effect of Polymer Concentrations on Characterisation and Ex Vivo Permeation Study

Purpose This study aimed to develop dissolving microneedle preparations containing ceftriaxone and evaluate the effect of polymer concentrations on characterisation and ex vivo permeation study. Methods The microneedles were prepared using centrifugation method with different ratios of PVP40% and PVA15%, namely FB1 (50:50), FB2 (60:40), and FB3 (70:30). The microneedles were also prepared with various concentrations of ceftriaxone, namely 10% w/w, 15% w/w, and 20% w/w. The microneedles were evaluated for their mechanical properties and ex vivo permeation profiles. Results The results showed that the microneedles were in the form of sharp pyramid with size ranging between 712 and 800 mu m. The concentration of ceftriaxone was found to affect the mechanical properties of the microneedles where formulations containing 20% w/w of ceftriaxone could not be produced. To achieve high drug loading, 15% w/w of ceftriaxone was selected in this study. Following the microneedle preparations, the formulation containing 15% w/w of ceftriaxone with FB3 polymer mixture exhibited the best mechanical properties with only 12.96 +/- 0.56% height reduction after the compression with 30 N pressure. Moreover, this formulation was able to penetrate 4 layers of Parafilm (R) layers, indicating adequate insertion properties. Importantly, the microneedles were found to dissolve completely after 10 min on the full thickness rat skin. The permeation study showed that the greater the concentration of PVA, the slower the permeation of ceftriaxone from the microneedles. The highest drug permeation was obtained by containing 15% w/w of ceftriaxone with PVP40%:PVA15% with the ratio of 70:30, with the percentage of 99.86 +/- 7.6%. The stability studies showed that the microneedles were stable for 1 month in two humidity levels, namely RH 43% and RH 86%. Conclusion Variation of polymer concentration exhibited a significant effect on the mechanical properties of microneedles. The permeation test showed that the greater the concentration of PVA, the slower the permeation of the active substance from dissolving microneedle. Further studies should be conducted to perform in vivo pharmacokinetic studies.

Automated summary

The study aimed to develop dissolving microneedle preparations containing ceftriaxone and evaluate the effect of polymer concentrations on characterization and ex vivo permeation study. The greater the concentration of PVA, the slower the permeation of the active substance from dissolving microneedle, showing significant effects on the mechanical properties of the microneedles.