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

This work describes Part 2 of multi-dose formulation development of a Human Papillomavirus (HPV) Virus-Like Particles (VLPs) containing vaccine (see Part 1 in companion paper). Storage stability studies with candidate multi-dose formulations containing individual or combinations of seven different antimicrobial preservatives (APs) were performed with quadrivalent HPV VLP (6, 11, 16, 18) antigens adsorbed to aluminum-salt adjuvant (Alhydrogel®). Real-time (up to two years, 2-8°C) and accelerated (months at 25 and 40°C) stability studies identified eight lead candidates as measured by antigen stability (competitive ELISA employing conformational serotype-specific mAbs), antimicrobial effectiveness (modified European Pharmacopeia assay), total protein content (SDS-PAGE), and AP concentration (RP-UHPLC). The AH-adsorbed HPV18 VLP component was most sensitive to AP-induced destabilization. Optimal quadrivalent antigen storage stability while maintaining antimicrobial effectiveness was observed with 2-phenoxyethanol, benzyl alcohol, chlorobutanol, and 2-phenoxyethanol + benzyl alcohol combination. Interestingly, for single-AP containing multi-dose formulations, this rank-ordering of storage stability did not correlate with previously reported biophysical measurements of AP-induced antigen destabilization. Moreover, other APs (e.g., m-cresol, phenol, parabens) described by others for inclusion in multi-dose HPV VLP formulations showed suboptimal stability. These results suggest that each HPV VLP vaccine candidate (e.g., different serotypes, expression systems, processes, adjuvants) will require customized multi-dose formulation development.

Abstract licence: CC BY