Percutaneous absorption of capsaicin, nonivamide and sodium nonivamide acetate from gel and ointment bases: In vitro formulation evaluations in pigs and in vivo bioengineering methods in humans

Nonivamide (NVA) and non-pungent sodium nonivamide acetate (SNA) are synthetic derivatives of capsaicin. In this study, in vitro formulation evaluations in pigs and in vivo bioengineering methods in humans were performed to obtain the information on percutaneous absorption for capsaicin, NVA and SNA. After the consideration of penetration capacity, skin irritation and physicochemical properties of the formulations in vitro, 0.6% Carbopol 940® gel form for capsaicin and NVA as well as 3.8% isopropyl myristate-added hydrophilic o/w ointment for SNA were utilized to study the following in vivo test in humans. In the study of in vivo surface recovery techniques, SNA showed an equivalent therapeutic capability to that of NVA after calculation of the antinociceptive index. After the quantification of skin erythema by laser Doppler flowmetry (LDF), capsaicin caused more severe irritation than NVA in humans. In addition, SNA showed no skin irritation, toxicity and pungent sensation. The transepidermal water loss (TEWL) values were determined using an evaporimeter. A comparison of the gel form showed there was significantly higher TEWL AUC values in capsaicin and NVA than in the control group. The AUC value of the hydrophilic ointment control group was significantly higher than that of the gel control group. The reason was that isopropyl myristate and sodium laurylsulfate, two additives incorporated in the hydrophilic base, could cause slight skin irritation resulting in the increase of TEWL. The results of this study suggest that SNA possesses potent antinociceptive activities after transdermal application. Furthermore, SNA can be used extensively in clinical therapy because it avoids any pungent skin sensation and burning pain to improve patients' compliance.