Chlorobutanol 1% tincture

Tranexamic acid (TA) is widely used clinically as a skin whitening agent for treating melasma and hyperpigmentation. However, oral administration of TA is often associated with adverse effects. Topical application could mitigate these issues, but the hydrophilic nature of TA limits its topical use. To overcome this limitation, we explored the design of TA alkyl ester prodrugs to enhance skin absorption. Our study specifically focused on the butyl and octyl ester derivatives of TA. The results demonstrated that TA4 and TA8 significantly improved skin penetration and deposition, by approximately 2-3 times compared to unmodified TA. Furthermore, these derivatives were rapidly hydrolyzed to release the parent drug within less than 2 h in both skin homogenates and blood. Safety assessments indicated no significant skin irritation in mice and revealed low cytotoxicity in HaCaT cells when exposed to the TA ester derivatives. We also developed a hydrogel formulation incorporating the TA derivatives, using hydroxyethyl cellulose, propylene glycol, Tween 80, and chlorobutanol. This formulation exhibited good skin absorption, stability, and user experience, making it a promising candidate for topical application. To sum up, the alkyl esterification prodrug design provides a promising approach for enhancing the skin delivery of TA.

Abstract licence: CC BY-NC

Chlorobutanol (CB) is used as a preservative in cosmetics and has antibacterial activity. This study investigated the single- and repeated-dose 28-day oral toxicity of a CB solvent in Sprague Dawley (SD) rats. For the single-dose oral toxicity study, a dose of 62.5, 125, or 250 mg per kg of body weight (mg/kg b.w.) of CB was given once orally via gavage. For the repeated-dose 28-day toxicity study, the high dose was set as 100 mg/kg b.w./day, and the middle, middle-low, and low doses were set to 50, 25, and 12.5 mg/kg b.w./day, respectively. Body weight was not significantly changed in the repeated-dose toxicity study. Relative liver and kidney weights were significantly increased in both sexes of the 100 mg/kg b.w./day treatment group. However, there were histopathological changes in liver and kidney for females and males, respectively. These data suggested that the approximate lethal dose (ALD) of CB was over 250 mg/kg b.w./day in the single-dose study, and the no adverse effect level (NOAEL) for CB was over 50 and 12.5 mg/kg b.w./day for female and male rats in the repeated-dose toxicity study.

Abstract licence: CC BY 4.0