Drug development and industrial pharmacy · 2026
Kinetic and biocatalytic evaluation of dodecyl nicotinate hydrolysis in aqueous buffers and biological media.
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Haddad Razan, Al-Taani Bashar, Al-Tarakji Aliaa, Alrabadi Nasr
Аннотация
OBJECTIVE: This study evaluated the hydrolytic behavior of dodecyl nicotinate under chemical and biological conditions to determine its suitability as a controlled-release prodrug of niacin.
SIGNIFICANCE: Niacin therapy is limited by a short half-life and dose-dependent flushing, which compromise adherence despite its lipid-modifying benefits. Prodrug design provides a strategy to enhance stability, prolong release, and facilitate enzymatic activation. Dodecyl nicotinate, a lipophilic C12 ester of niacin, is expected to balance membrane permeability with enzymatic lability. While shorter (octyl) and longer (myristyl) analogs have been examined, systematic kinetic data for the C12 ester remain scarce. This study provides new insights into its stability and enzymatic conversion, highlighting translational potential for oral and transdermal controlled-release systems.
METHODS: Hydrolysis kinetics were investigated in buffered aqueous media (pH 5-10) at 80 °C using HPLC. Pseudo-first-order rate constants and pH-rate profiles were derived, and buffer catalysis was assessed in phosphate, borate, and carbonate systems. Enzymatic hydrolysis was studied in rat liver and skin homogenates at 37 °C, with Michaelis-Menten modeling applied to characterize kinetics.
RESULTS: Dodecyl nicotinate showed pH-dependent pseudo-first-order hydrolysis, with carbonate buffer exerting the greatest catalytic effect. Enzymatic cleavage was markedly faster than chemical hydrolysis, with half-lives of 24.8 min in liver and 63 min in skin homogenates. Michaelis-Menten analysis confirmed saturable enzyme kinetics.
CONCLUSIONS: Dodecyl nicotinate combines chemical stability with efficient tissue-mediated bioconversion, supporting its promise as a controlled-release niacin prodrug suitable for both oral and transdermal delivery.
SIGNIFICANCE: Niacin therapy is limited by a short half-life and dose-dependent flushing, which compromise adherence despite its lipid-modifying benefits. Prodrug design provides a strategy to enhance stability, prolong release, and facilitate enzymatic activation. Dodecyl nicotinate, a lipophilic C12 ester of niacin, is expected to balance membrane permeability with enzymatic lability. While shorter (octyl) and longer (myristyl) analogs have been examined, systematic kinetic data for the C12 ester remain scarce. This study provides new insights into its stability and enzymatic conversion, highlighting translational potential for oral and transdermal controlled-release systems.
METHODS: Hydrolysis kinetics were investigated in buffered aqueous media (pH 5-10) at 80 °C using HPLC. Pseudo-first-order rate constants and pH-rate profiles were derived, and buffer catalysis was assessed in phosphate, borate, and carbonate systems. Enzymatic hydrolysis was studied in rat liver and skin homogenates at 37 °C, with Michaelis-Menten modeling applied to characterize kinetics.
RESULTS: Dodecyl nicotinate showed pH-dependent pseudo-first-order hydrolysis, with carbonate buffer exerting the greatest catalytic effect. Enzymatic cleavage was markedly faster than chemical hydrolysis, with half-lives of 24.8 min in liver and 63 min in skin homogenates. Michaelis-Menten analysis confirmed saturable enzyme kinetics.
CONCLUSIONS: Dodecyl nicotinate combines chemical stability with efficient tissue-mediated bioconversion, supporting its promise as a controlled-release niacin prodrug suitable for both oral and transdermal delivery.