NANOCAPSULE

cONTENT INTRODUCTION ADVAVTAGES OF NANOCAPSULE NEED TO STUDY NANOCAPSULE STRUCTURES OF NANOCAPSULE METHOD OF PREPARATION OF NANOCAPSULE CHARACTERISATION OF NANOCAPSULE REFERENCES

INTRODUCTION Nanocapsules is a advanced technique of nanotechnology. Nanoparticle defined as a submicronic colloidal systems made of polymer preferably biodegradable nanoparticle are at least ten times smaller than microparticles which allows them to be administer intravenously with out any risk . Nanosphere in matrix system in which solid drug dispersed within the polymer through the particle

CONT… Nanocapsule can be defined as nano-vesicular systems that exhibit a typical core-shell structure in which the drug is confined to a reservoir or within a cavity surrounded by a polymer membrane or coating . The cavity can contain the active substance in liquid or solid form . Nanoencapsulation involves forming drug loaded particles with diameters ranging from 1 to 1000 nm.

CoNT.. Nanoparticle Nanospheres Nanocapsule

Advantages of nanocapsules Higher dose loading Reduce irritation of drug at site of administration. Greater protection from degradation during storage & after administration. Site specific action. Increase bioavailability of drug. control and sustain release of the drug at the site of localization. The system can be used for various routes of administration including oral, nasal, parenteral, intra-ocular etc Improve patient compliance.

Need to study nanocapsule Their main use is to – 1. Minimize drug degradation upon administration, 2. Prevent undesirable side effects, 3. Increase drug bioavailability, 4.Nanoparticulate carriers can be targeted to specific cells and locations within the body after intravenous and subcutaneous routes of injection.

Structure of nanocapsule

Method of preparation of nanocapsules Nanoprecipitation method Emulsion–diffusion method Double emulsification method Emulsion-coacervation method Polymer-coating method

General formula of Nanoprecipitation method Material Suggested Composition Active substance 10-25mg Polymer 0.2-0.5% of solvent Oil 1.0-5.0% of solvent W/O Surfactant Solvent 25ml Stabilizer agent 0.2-0.5% of non-solvent Non-solvent 50ml

Nanoprecipitation method Slow injection (Dropwise and moderate stirring Organic phase Aqueous phase

Fig1.Set-up used for preparation of nanocapsules by the nanoprecipitation method.

Example of drugs Drugs Polymer Oil Core Solvent Activity Indomethacine PCL Mw 60 kDa Mineral oil Acetone Anti-inflammatory

General formula of Emulsion–diffusion method Material Suggested Composition Active substance 10-50mg Polymer 1.0-2.0% of inner phase solvent Oil 2.5-5.0% of inner phase solvent Inner phase solvent 10ml Stabilizer agent 2.0-5.0% of external phase solvent External phase solvent 40ml Dilution phase 200ml

Emulsiol diffusion method Dilution Phase Dilution Phase Organic Phase Emulsification (High shear mixer) Emulsification (High shear mixer) Diffusion (Moderate stirring) Diffusion (Moderate stirring) Aqueous phase

Fig2. Set-up used for preparation of nanocapsules by the emulsion–diffusion method.

Example of drug Drug Inner phase Polymer core solvent1 External phase Stabilizer solvent2 agent Dilution phase Use Indomethacine PCL Mw 10 Caprylic Triglyceride Ethyl acetate PVA poloxamer Water water Anti-inflamatory

General formula of Double emulsification method Material Suggested composition A)Inner aqueous phase a)Active substance 0.5-25mg. b)Water 0.15-0.5ml. B)Organic phase a)Polymer 5-10% of organic phase solvent. b)W/O surfactant 5-7 % of organic phase solvent c)Solvent 1.5-5 ml C)External aqueous phase a)Stabilizer agent 1-5% of external aq. Phase solvent. 2 – 5 ml.

Double emulsification method Aqueous Phase2 Organic Phase Emulsification W/O (Sonication) Emulsification (Sonication or high shear mixer) Aqueous Phase1

Fig3. Set-up used for preparation of nanocapsules by the double emulsification method.

Example of drug Drug W1 phase Organic phase W2 phase Use Insulin Active ingredient, water PLA Mw 10 kda , DCM, Sorbitan monoleate Polysorbate 80,60 or 20, Glycerin:water antidiabetic

Emulsion-coacervation method Coacervating agent Organic phase Emulsification (machanical stirring or sonication) Coacervation (moderate stirring) Aqueous phase

Fig4. Set-up used for preparation of nanocapsules by the emulsion-coacervation method.

Example of drug Drug Polymer Core Organic Phase Aqueous phase Cross linking agent Use Turmeric oil Sodium alginate Mw 80-120kDa organic Ethanol or methanol Sodium alginate, Polysorbate80, Water Calcium chloride Antifungal Antibacteial Antioxidant

Polymer-coating method solvent removal Oil phase Formation of polymer coat Emulsification o/w (sonication) Aqueous phase

Fig5.Set-up used for preparation of nanocapsules by the polymer-coating method

Example of drug Drug Organic phase Aqueous phase coating Use Salmon calcitonin Active ingredient, Caprylic triglycerides, acetone Poloxamer 188, water Chitosan oligomers Calcium regulator

Concentration Purification Stabilisation Nanoprecipitation,emulsion diffusion,double emulcification,emulsion coacervation,polymer coating Concentration (magnetic agitation,evaporation by vacuum) Purification (water washing,gel filtration) Stabilisation (spray drying,Lyophilisation)

Characterization of Nanocapsules Nanocapsule zeta-potential Nanocapsule dispersion pH Nanocapsule shell thickness Nanocapsule encapsulation efficiency

References C.E. Mora-Huertasa, H. Fessi , A. Elaissari ,International Journal of Pharmaceutics-Polymer-based nanocapsules for drug delivery, Université de Lyon, F-69622, Lyon, France. Nanoencapsulation - Methods for preparation of drug-loaded polymeric nanoparticles, Catarina Pinto Reis, Ronald J. Neufeld, Anto´ nio J. Ribeiro, Francisco Veiga. Nagavarma B.V. , Hemant K.S.Yadav, Ayaz A, Vasudha L.S, Shivakumar H.G Asian Journal of Pharmaceutical and Clinical Research , Vol 5, Suppl 3, 2012.

CONT.. I. Valente, L. J. del Valle, M. T. Casas, L. Franco1 A. Rodríguez-Galán, J. Puiggalí,D. Marchisio1, Nanospheres and nanocapsules of amphiphilic copolymers, Vol.7, Department Enginyeria Química, E-08028 Barcelona, Spain. www.elsevier.com/locate/ijpharm