Improved transdermal delivery of valsartan using combinatorial approach of polymeric transdermal hydrogels and solid microneedles: an ex vivo proof of concept investigation.

Valsartan (VAL) is used as a first-line agent to treat hypertension. However, VAL exhibits poor absorption and low bioavailability when administrated orally. To overcome these issues, VAL transdermal gel was developed in this study, where Carbopol was used as the gel matrices. Additionally, solid microneedles (Dermaroller®) with various needle lengths were combined with transdermal gel to improve its permeation across the stratum corneum as a skin barrier. Developed formulations were further evaluated for various parameters, including pH, viscosity, spreadability, extrudability, gel strength, drug content, ex vivo permeation, in vitro release, occlusivity, and hemolysis. The results showed that all formulations exhibited desired physical characteristics without any potential to cause toxicity. Moreover, this approach showed that using microneedles could significantly enhance the permeation of VAL up to 3 folds compared to untreated skin. The use of microneedles 1.5 mm was found to be the optimum combination to improve VA permeation without affecting skin integrity. As much as 1.69 ± 0.004 mg of VAL permeated after 8 h. Finally, it could be concluded that this work had successfully developed a new approach for VALS drug delivery and could potentially show a significant impact on the treatment of hypertension. Further in vivo work should be considered.

Combinatorial Approach of Thermosensitive Hydrogels and Solid Microneedles to Improve Transdermal Delivery of Valsartan: an In Vivo Proof of Concept Study.

Due to the limitations of oral administration of valsartan, in this study, we aimed to develop thermosensitive hydrogel for sustained transdermal delivery and improved bioavailability of valsartan, which was further improved using solid microneedles. The thermosensitive gel formula was made using Poloxamer 407 and Poloxamer 188 in various ratios. Valsartan thermosensitive gels were evaluated for their gelation temperature, pH values, drug content, spreadability, viscosity, rheological properties, in vitro drug release, in vitro permeation, and ex vivo permeation. Finally, in vivo study was conducted, compared to oral administration. The results presented the formulations showed required characteristic for transdermal administration with desired thermosensitive properties. Based on the permeation test with and without microneedles, it was found that the use of microneedles could affect the permeation of valsartan. Specifically, the increase of microneedles' needle length also increased valsartan permeation. The combination with the highest permeation was produced by 1.55 mm MNs with the amount of drug permeated of 2.27 ± 0.01 mg. Importantly, the transdermal delivery of valsartan using this combination approach could significantly improve the bioavailability of valsartan in in vivo study. The concentration of poloxamer was able to affect the properties of the hydrogels, and the use of solid microneedles improved the transdermal delivery of valsartan. In vivo studies showed the improvement of the bioavailability of valsartan compared to oral administration, showing the effectiveness of this combination approach.