Microencapsulation & Delivery systems

Transcription

1 Microencapsulation & Delivery systems A new activity at SEPPIC January 2010

2 Introduction: Definitions Microencapsulation Isolation of an active ingredient from the external environment (protection of the active material or of the workers) thanks to a liquid or a solid barrier. Active ingredient Controlled release Release of the active ingredient thanks to a trigger at the right place, and at the right moment, according to a desired kinetics active ingredient doesn t mean pharmaceutical active molecule 2

3 Different types of capsules Membranes Active ingredient Membrane Matrices Active ingredient Matrix Inclusions or sponges Active ingredient Solid porous support 3

4 Microcapsules: Main manufacturing processes Solid membranes - Film coating, interfacial polymerization, hot melt coating - Coacervation Liquid membranes - Liposomes, emulsions Matrices - Prilling ; dripping - Solvent evaporation - Compression - Polymer precipitation - Granulation (wet or spray drying) - Solid dispersion (SLN) - Extrusion SEPPIC s Know how Inclusions - Absorption in (or on) solid porous supports - Resinates - Complexation in cyclodextrines 4

5 Choice of an encapsulation technology There is no universal technology The best choice depends on: Active ingredient The type and the size of desired microcapsule The characteristics of the active ingredient The type of trigger The desired kinetics of release The medium where the active ingredient must be released The acceptable cost 5

6 Encapsulation processes choices: guidelines Properties of the desired microcapsules Properties of the active ingredient Solid, with a size of about Liquid, with a size of about < 100 µm µm >5000 µm µm µm Coacervation + emulsion E/H Atomisation Compression Emulsification (W/O) Solid hydrophilic Resinates Granulation Coating If Ø >100µm* Absorption If Ø <10µm* Granulation Coating If Ø >5000µm* Micro Emulsification (W/O) Gel in Oil Granulation Atomisation Compression Solid hydrophobic Liquid hydrophilic Emulsification (solid lipidic matrices) Coacervation Coacervation + emulsion E/H Resinates Coacervation Absorption If Ø <10µm* Coating If Ø >100µm* Absorption Granulation Atomisation Granulation Coating If Ø >5000µm Absorption + compression Granulation Micro Emulsification (O/W)) Micro Emulsification (W/O) Emulsification (O/W) Emulsification (W/O) Absorption Absorption + compression Emulsification (O/W) Liquid hydrophobic Coacervation Granulation Atomisation Coacervation Granulation Solubilization Emulsification (O/W suspension) 6

7 Emulsions - Liquid membranes External Medium (biological acquaeous medium) Surfactant W/O emulsiongel in oil em 10 Volume (%) µm Particle Diameter (µm.) Internal Water Internal Gel Size distribution of a gel in oil emulsion 7

8 Emulsions - liquid membranes Experimental device Release profiles can be monitored and predicted by mathematical models Montanide DDS 51 F: mineral oil Montanide DDS 763A: ester Montanide DDS 720: squalene Release of encapsulated caffeine 8

9 Coatings Mechanism of film formation Spraying Wetting Drying Film formation Particule Droplet of coating solution Laboratory and pilot equipment in SEPPIC s labs Ventilated pan coater Fluidized bed 9

10 Granulation Wet granulation Atomisation 10

11 Hydrophilic matrices (compression) Hydrophilic matrices made of hypromellose -- Predicted kinetics of dissolution Desired kinetics of dissolution 6 punch rotative tabletting machine in SEPPIC s lab HYMAT model is able to calculate the suitable tablet composition to achieve a predefined release profile of an active ingredient. Dissolution device 11

12 Hydrophilic pearls (dripping) Alginate and PVA pearls Solution of sodium Alginate and active ingredient 100 Microbeads Alginate /Volatile biocide 50/ Non encapsulated biocide % biocide weight loss Encapsulated biocide in alginate capsules: Not crosslinked Crosslinked with 2% of Glutaraldehyde Crosslinked with 5% of Glutaraldehyde 10 Gelation bath (CaCl2 solution) Time ( hours ) Ex: Release of kinetics of a volatile biocide encapsulated in alginate microcapsules 12

13 Hydrophobic pearls (Prilling) This technology is suitable to encapsulate hydrophobic ingredients or suspensions, in fatty materials having adapted melting points (i.e. surfactants). Several types of devices allow the formation of regular pearls from 100 to 2000µm in size Simple Nozzle Rezonnance nozzle Rotative or spinning disk Melted material Cold air or water 13

14 Hydrophobic pearls (Prilling) % of released API time ( hours) Release of an API from an micropearl containing 50% of pharmaceutical surfactants and 50% of API 14

15 Coacervation To encapsulate hydrophobic ingredient only SEPPIC collaboration with Hallcrest UK 15

16 Coacervation 16

17 "Inclusions" or "sponges" Porous solid support: - Organic or mineral - Ionic or neutral Active ingredient If ionic support -> ion exchange resins: Some of our results: Alumino silicates + Surfactant for uses in tablets (Sepitrap range) Alumino silicates + perfumes for home care applications Cellulosic Granules + pigments for pharmaceutical coating compositions (Sepifilm Jet range) Cellulosic Granules + Drugs for uses in tablets 17

18 "Coated sponges" Porous solid support Coating additive (surfactant, fat, polymer ) Active ingredient Perfume release according to time 0% % -4% Weight losses Perfume on coated solid support -6% -8% Perfume on solid support Perfume alone -10% -12% Days 18

19 SEPPIC organisation for encapsulation and Delivery Systems A dedicated technological Platform A dedicated team Contacts: yves.duccini@airliquide.com gerard.trouve@airliquide.com Our goals: To develop partnerships with our customers To optimize and manufacture microcapsules containing their active ingredients according to their requirements To deliver ready to use microcapsules 19

20 Platform - Customer relationships A 3 step process 1. Visit, discussion and establishment of technical and economical requirements under NDA (if customer needs) 2. Feasibility study, free of charge 3. Charged contract development, including technical steps, timing, fees, IP repartition Technical studies : lab, pilot, industrial batch. Samples are provided to the customer at each step, for a validation. 20

21 Why choose SEPPIC? Our strengths and specificities A global solution from the raw material to the microcapsule A range of supplementary technologies Industrial manufacturing capacities. The possibility to develop specific raw material to obtain optimized capsules. 21