Cours encapsulation evaporation_240801_095309.pdf

3. How to perform Microencapsulation ? ✓ Processing aspects 3 encapsulation processes Mechanical Physico-chemical Polymers Chemical...

3. How to perform Microencapsulation ? ✓ Processing aspects 3 encapsulation processes Mechanical Physico-chemical Polymers Chemical 1  ✓ Polymer - Preformed synthetic or natural polymer  Mechanical and physico-chemical processes Emulsion- solvent evaporation encapsulation process - in situ formed during the encapsulation process  Chemical encapsulation technique Interfacial polymerization encapsulation process 2  ✓ Encapsulation droplets spheres 1st step : emulsification step Encapsulation droplets capsules 3 3.1- Emulsion- Solvent Evaporation ✓ Formation of microspheres or microcapsules Mechanism vacuum Dissolution or dispersion of the active agent in an organic polymer solution: volatile solvent o/w or double w/o/w emulsion Removal of the organic solvent under stirring  extraction and evaporation Solubility in water Boiling point 4  Polylactic acid, Polyglycolic acid Polymer Polystyrene, PMMA Ethylcellulose, Eudragit Solvent Dichloromethane, Chloroform, Ethyl acetate lipophilic (steroids, vitamin…) Encapsulated agent Hydrophilic (dyes) 5 Microspheres Hydrophobic active agent ✓ Hydrophobic active agent Polymer Water Volatile solvent + Surfactant Solvent evaporation Polymer initial state: o/w emulsion final step = microspheres 6 Microspheres ✓ Hydrophilic active agent initial state: w/o emulsion Organic phase less volatile than water  Tb > 100°C  caution: thermal degradation of the active agent 7  Microcapsules Hydrophobic active agent ✓  addition of a miscible non-volatile solvent to the organic volatile one = inert oil Inert oil must dissolve the active agent but not the polymer Inert oil is miscible with the volatile solvent When the volatile solvent evaporates, the polymer precipitates entrapping the inert oil According to the interfacial tension between the inert oil and the polymer, there will be the formation of microcapsules with - either monocompartmental core (high interfacial tension) - or pluri compartmental core (low interfacial core) Increase of the interfacial tension between the inert oil and the polymer Coalescence of the oil droplets according to the interfacial tension between inert oil and polymer 9  Internal morphology = f(interfacial tensions between the different substances) f(evaporation rate of the organic solvent) DCM 130 min CHCl3 200 min gMio /pol= 32 mN/m gMio/pol = 23 mN/m 10 P. Valot, Thèse Lyon1, 2007  Microcapsules Hydrophilic active agent ✓  Double emulsion Double emulsion Préparation of a primary w/o emulsion with an aqueous soluble agent Sonication or Ultra turrax Rapid transfert of the primary emulsion in the aqueous continuous phase w/o/w Water+surfactant Water+surfactant Hydrophilic active agent Polymer Polymer Volatile solvent Hydrophilic active agent Initial state Final state = particles with aqueous core = mono or polynuclear Microcapsules 11 Double emulsion Surfactant in the continuous phase Sometimes surfactant in the oil phase too 12 Taille et Morphologie ✓ Conditions expérimentales d’évaporation  taille, morphologie, surface spécifique  libération du principe actif Méthode d’évaporation (température, pression) Vitesse d’évaporation Ratio Volume phase Dispersée/continue Concentration en polymère = paramètres critiques Concentration en TA Solubilité solvant organique/eau Affinité du polymère avec eau 13  ✓ Influence de la vitesse d’évaporation du solvant organique volatil  État de surface des microsphères Surface rugueuse/poreuse   surface spécifique   libération (burst effect) 14  ✓  Vitesse d’élimination du solvant rapide  Concentration en polymère élevée  solidification rapide de la surface des gouttes  Teneur en principe actif + élevée, porosité + faible, solvant résiduel + important 15 Preparation of poly(l-lactide) microspheres of different crystalline morphology and ✓ effect of crystalline morphology on drug release J. Controlled Release, 1991 Evaporation rapide Evaporation à pression atmosphérique Rugueuse poreuse Lisse et dense  Vitesse d’élimination du solvant rapide  faible surface spécifique,  cinétique de libération lente  densité en volume élevée  ✓ ASE RSE 17 17  Influence of the nature of the volatile organic solvent ✓ Ø = f(evaporation and diffusion of the organic solvent) Tb(DCM) = 40°C Tb(CF) = 70°C Solubility of CH2Cl2 in water = 1,961 wt% T =25°C ; CHCl3 = 0,815 wt% Diffusion and rapid evaporation  viscosity of fd     18 P. Valot, Thèse Lyon1, 2007   Compléments Nature of the non-volatile organic solvent Benzyl benzoate Vitamin E Miglyol 812 Vit E : 0,0290 mg/mL Solubility Parameters/solubility in water BB : 0,0154 mg/mL Mi : 0,0030 mg/mL 19 P. Valot, Thèse Lyon1, 2007   Compléments Influence of the volume of the dispersed phase Polymer amount is constant Size distributions of Ibuprofen-loaded Eudragit RSPO microcapsules obtained with a dispersed phase volume equal to 40mL (), 80mL () and 160mL (). Vd     Vd   hd  because [polymer]  20 P. Valot, Thèse Lyon1, 2007   Compléments Influence of the volume of the continuous phase Effect of jc volume  diffusion of the volatile organic solvent The volume of the aqueous external phase higher is it, higher is the diffusion of the organic solvent Higher is the viscosity of the internal phase  a too high volume of aqueous external phase  stirring system unefficient    and large size distribution 21   Compléments Influence of the stirring rate 22 P. Valot, Thèse Lyon1, 2007