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Nguyen Huu-Manh,Duong The-Khang,Nguyen Van-Khuyen,Nguyen Thi-Khanh-Ly,Dong Thi-Hoang-Yen,Nguyen Canh-Hung,Tung Nguyen-Thach 한국약제학회 2024 Journal of Pharmaceutical Investigation Vol.54 No.2
Purpose A two-step experimental design was used to develop a lornoxicam (LOR)-loaded topical hydrogel patch. We specifically focused on the simultaneous effect of the ion pair formation agent (triethanolamine [TEA]) and the chemical enhancer (cremophor RH40 [RH40]) on flux and conducted physicochemical studies and skin physiology assessments to obtain further information. Methods Drug-in-adhesive patches were fabricated using a micrometer-adjustable film applicator. The applied Design of Experiments (DoE) approach consisted of the Fractional Factorial Resolution V + design and the Central Composite Face design established by the MODDE® 12.0 software. Molecular-level drug-excipient interactions were investigated using infrared (IR) and proton nuclear magnetic resonance (1H NMR) spectroscopy. The effects on skin physiological function was assessed using DermaLab Combo. Results DoE results revealed that TEA enhanced flux by 3.14-fold, whereas RH40 reduced it by 4.62-fold. The addition of RH40 resulted in the disappearance of the proton peak within the region of 12–13 ppm, suggesting competition for hydrogen bonding with LOR between TEA and RH40. The optimized formulation (4% TEA, 0% RH40, and 0.2% Al(OH)3) increased skin hydration by 6.20-fold. Opposing effects of TEA and RH40 on skin elasticity were observed. Conclusion Expected flux and adhesion strength for the optimized formulation were 7.18 μg·cm–2·h–1 and 11.79 mJ, respectively. Our understanding of the conflicting effects of TEA and RH40 has been advanced. The integrated use of the two-step DoE, physicochemical studies, and skin physiology assessments was proven to be effective in elucidating the simultaneous effects of different permeation-modifying strategies on patches, thus having substantial value for the successful execution of future research endeavors.