外用制剂应用后的变化及其对皮肤特性与活性成分渗透的影响

该博士项目将利用共聚焦拉曼光谱和流变学等技术，研究局部制剂在皮肤应用后的动态变化。研究旨在揭示这些变化如何影响药物渗透及产品性能的机制。申请者应拥有药学或相关领域的硕士学位。

Job description: Project description: After application to the skin, topical formulations undergo dynamic transformations driven by solvent evaporation, microstructural changes and rearrangement of their constituents. These processes can modify the residual film, the state of the active substance and interactions with the skin, with consequences for drug penetration. Characterisation of the product before application may therefore be insufficient to explain its performance under conditions of use. This doctoral project, part of the European guideSkin doctoral network, aims to establish a mechanistic framework linking post-application formulation transformations to skin penetration and product performance. The research will be conducted at the Faculty of Pharmacy, Université Paris-Saclay, in collaboration with RaDes GmbH in Germany and LVMH Recherche in France. The work will combine white-light and polarised-light microscopy, rheological measurements (rotational, oscillatory and thixotropic), and water evaporation measurements to characterise changes in formulation microstructure and properties over time. Confocal Raman spectroscopy will be used to monitor formulation transformation and skin penetration in parallel, complemented by in vitro permeation testing (IVPT) to assess how these transformations affect drug permeation. Chemometric and multivariate statistical approaches will relate formulation composition, evaporation kinetics, microstructural and rheological changes, and penetration outcomes. The project will investigate the physicochemical and thermodynamic factors governing these relationships, including residue formation and changes in the state of the active substance where relevant. Expected outcomes include characterisation protocols, descriptors of post-application transformation and experimental datasets linking these changes to skin penetration and permeation. The datasets will support modelling activities in DC06 and DC08 and contribute to improved assessment of topical product performance and pharmaceutical equivalence. The doctoral training includes industrial secondments of 12 months at RaDes for formulation manufacture and characterisation, and 6 months at LVMH Recherche for product performance testing.

Profile and skills required: Eligibility conditions: • Master’s degree in pharmaceutics, pharmaceutical technology, pharmaceutical sciences, physical chemistry or a closely related discipline, with relevant training or research experience in formulation science. • Applicants must be doctoral candidates, i.e not already in possession of a doctoral degree. • Mobility rule: researchers must not have resided or carried out their main activity in the country of the recruiting beneficiary for more than 12 months in the 36 months immediately before their recruitment date. Required skills: • Solid knowledge on pharmaceutical technology, ideally with prior knowledge on the design and analyticial , physico-chemical and/or biopharmaceutical evaluation of semi-solid formulations for cutaneous use. • Practical laboratory experience in formulation preparation, physicochemical characterisation or a related experimental discipline. • Competence in experimental design, quantitative data analysis and critical interpretation of scientific results. Experience using scientific data-analysis software and willingness to develop skills in chemometrics and reproducible data processing. • Ability to work independently and collaboratively within an international academic–industrial research team, and to communicate scientific findings clearly. • Proficiency in the English language is required, as well as good communication skills, both oral and written. Successful candidates will need to provide an English test (e.g. IELTS, TOEFL, Cambridge English). You may be exempt if you are a national of a majority native-English speaking country, or have qualifications / degree that has been taught and assessed in English. The supervisor may also confirm that a candidate has the required level of English. Desirable experience • Experience in one or more of the following: semi-solid formulation development, rheology, optical microscopy, Raman spectroscopy, evaporation measurements or in vitro release/permeation testing. • Familiarity with multivariate statistics, spectroscopic data analysis or programming in Python, R or MATLAB. Niveau d'anglais requis: Intermédiaire supérieur: Vous pouvez utiliser la langue de manière efficace et vous exprimer précisément.