Enhanced and sustained transdermal delivery of primaquine from polymeric thermoresponsive hydrogels in combination with Dermarollers®

Abstract

Primaquine (PMQ) is an effective antimalaria drug with several limitations. We report the combinatorial approach of thermoresponsive hydrogels and Dermarollers® for transdermal delivery of PMQ to overcome these limitations. The hydrogels were prepared using Pluronic F127 (PF127) and F68 (PF68). Specifically, HPMC was added into the formulation to improve the bioadhesive properties. Numerous formulations were prepared, showing that formulation comprising 15 % PF127, 3 % PF68 and 0.4 % HPMC with 1 % PMQ was selected as the optimum formulation. The formulation showed the gelation temperature around 35 °C with bioadhesive strength of 26.43 ± 2.31 dyne.cm2. Importantly, the pH of the formulation was suitable for skin application with the percentage of PMQ recovery of 99.57 ± 3.23 %. Moreover, the hydrogels exhibited free-flow liquid at storage and room temperature and high viscosities in the skin temperature. In vitro release experiments showed that the release of PMQ was sustained for 24 h. Evaluated in extensive ex vivo studies, the treatment with Dermarollers® improved the skin permeation and retention of PMQ for 3 days. In combination with Dermarollers®, the ex vivo permeation of PMQ was sustained and the localization of PMQ in the skin was improved over 72 h.