The skin is the main barrier to regulate the permeation of substances and protect the internal body organs. Despite extensive experimental research, a systematic in silico study has not been conducted on formulation effect on skin permeation. Formulation effect on skin permeation was investigated based on two main factors: formulation evaporation and penetration enhancement. A state of the art in-silico model was developed to predict skin permeation along with the formulation evaporation. The model was used to analyse the skin permeation of diclofenac sodium from PG and water mixture as well as glycerol and water mixture. Although the model predicted drug permeation from PG and water mixture well, the model was unable to predict the skin permeation from glycerol and water mixture showing the limitations of the model. The model is applicable only for solutions that behave ideally or that have a behaviour that can be predicted by UNIFAC or COSMOtherm like models. The model can be applied only when thermodynamic activity is the main driving force. Additionally, another empirical model was developed based on literature data to predict modified skin to water partition coefficient due to solvent effect, and penetration enhancement was quantified based on that. Literature data of ibuprofen skin permeation from PG and water binary mixtures were used to show the model capability. The model predicted skin permeation of an infinite dose as well as a finite dose and compared well with literature data. This methodology can be extended to predict skin permeation from other ingredients too.

This study enables designing effective topical medications, optimizing drug formulations to improve the efficacy, and it can be considered in toxicology and safety assessments. It improves the understanding of the skin research and reduce the animal testing. This research study ultimately supports the regulatory bodies to update the regulatory guidelines.