Thèse Atomisation Vs Lyophilisation pour la Microencapsulation Compréhension Mécanistique des Relations Formulation-Procédé-Microstructure à l'Échelle Moléculaire pour Maîtriser Stabilité et Libér H/F - 69

Établissement : Université Claude Bernard Lyon 1
École doctorale : Chimie de Lyon
Laboratoire de recherche : LAGEPP - Laboratoire d'Automatique, de Génie des Procédés et de Génie Pharmaceutique
Direction de la thèse : Severine VESSOT-CRASTES
Début de la thèse : 2026-10-01
Date limite de candidature : 2026-04-24T23:59:59

Microencapsulation is widely used to protect sensitive compounds and to tailor their release, yet the choice
between spray-drying and freeze-drying is still largely empirical. These two processes generate markedly
different dried architectures (skin formation and internal gradients vs porous networks shaped by freezing and
sublimation), resulting in distinct stability and release behaviours. This PhD project aims to establish a
mechanistic and quantitative comparison between spray-drying and freeze-drying, linking molecular/colloidal
interactions in the feed formulation to process-driven microstructure, and ultimately to stability and release
kinetics. The work will deliver robust descriptors (e.g., water activity, sorption, glass transition temperature,
plasticization, porosity, internal distribution) and provide predictive guidelines to rationally select and design
drying routes for microencapsulation across applications.

- Establish a harmonized comparative framework for spray-drying vs freeze-drying.
- Identify robust physico-chemical descriptors explaining stability and release (aw, sorption isotherms,
Tg/plasticization, porosity, morphology, internal distribution).
- Elucidate how molecular interactions in the feed drive process response and final microstructure.
- Deliver transferable design rules (formulation × process microstructure performance) using DoE
and multivariate analysis.

Task 1 - Model formulations and molecular interactions (pre-drying): Biopolymer matrices (proteins,
polysaccharides, mixed systems) tuned by composition, pH and ionic strength; characterization of colloidal
state and interaction regimes (size, -potential, rheology, relevant thermal/spectroscopic indicators depending
on available equipment).
Task 2 - Spray-drying: microstructure genesis and gradients: Systematic variation of key operating
parameters (solids content, viscosity window, atomization conditions, inlet/outlet temperatures);
measurement of particle/powder properties (size distribution, moisture, aw, morphology, density,
redispersibility) and encapsulation/retention.
Task 3 - Freeze-drying: freezing-driven porosity and structural stability: Investigation of freezing conditions
and cycle parameters (primary/secondary drying, thermal limits/collapse); quantification of pore structure, Tg,
rehydration kinetics and functional properties.
Task 4 - Stability and controlled release: Accelerated storage under controlled T/RH; modelling of
retention/degradation; release kinetics in model media (pH/ionic strength) with mechanistic modelling
(diffusion/swelling/erosion) linked to microstructure descriptors.
Task 5 - Data-driven comparison and optimisation: Design of experiments, response surface modelling and
multivariate analyses to map process-structure-property relationships and generate predictive guidelines.