Investigation of the permeation enhancer strategy on benzoylaconitine transdermal patch: the relationship between transdermal enhancement strength and physicochemical properties of permeation enhancer

Permeation enhancer strategy is used to develop Benzoylaconitine (BA) of high molecular weight (603.7 Da) into transdermal patch. The present study was to achieve a patch with good analgesic and anti-inflammatory effects and investigate the relationship between physicochemical parameters of enhancers and enhancement strength. In vitro skin permeation study was used to evaluate the effect of enhancers, and correlation study was conducted to clarify the relationship between physicochemical parameters of enhancer and permeation amount. The enhancement molecular mechanism was characterized using FT-IR and molecular modeling. Finally, pharmacodynamic effect of BA patch was evaluated with analgesic and anti-inflammatory assessment. The correlation analysis indicated that the optimized patch containing permeation enhancer Plurol® Oleique CC497 with high surface tension (43.0 dyne/m), demonstrated the strongest skin permeation amount of 5.50 ± 0.21 μg/cm2. According to the FT-IR and molecular modeling study, the enhancer with high surface tension demonstrated maximum interaction strength (Emix = −9.20 kcal/mol) with skin lipid and affected the skin protein region, which strongly disturbed skin lipid arrangement according to the results of ATR-FTIR study (wavenumber variation of νas CH2 of skin lipid > 2.00 cm−1) and molecular modeling (Cohesive Energy Density of skin lipid bilayer = 1.04E + 08 kcal/mol). It was indicated that only based on sufficient interaction strength and disturbing of both lipophilic and hydrophilic area of stratum corneum, permeation enhancer was able to demonstrated great permeation enhancement effect. Finally, BA transdermal patch was developed and showed excellent analgesic and anti-inflammatory effect, which was a potential preparation for the treatment of inflammatory pain. [Display omitted]