Nanoformulation

Including SMEDS &SNEDS

1. Solid-lipid nanoparticle Nano structure lipid carrier Nanosuspension SMEDS/SNEDS Presented by Mr.Khillare Khillare Madhav B.Pharm Final year Under the Guidenance Ms.Tiwari S.Madam PHARMANANO FORMULATION

2. SOLID LIPID NANOPARTICLE NANOSTRUCTURE LIPID CARRIER NANOSUSPENSION SMEDS/SNEDS PHARMANANO FORMULATION

3. INTRODUCTION Solid lipid nanoparticle posses a solid lipid core matrix that can solubilize liphophilic molecule. A solid lipid nanoparticle is typically spherical with an avarage diameter between 10 to 1000 nm SLN offer unique properties such as small size, large surface area, high drug loading Solid lipid nanoparticle(SLN)

4. Control and / or target drug release. • Excellent biocompatibility . • Easy to scale up and sterilize. • Enhanced bioavailability • Chemical protection of labile incorporated compounds . • Improve stability of pharmaceutics. Disadvantages of SLN • Particle growth. • Unpredictable gelation tendency. • Unexpected dynamics of polymeric transitions Advantages of SLN

5. • Possibility of controlled drug release. • Increased drug stability . • High drug pay load. • No bio-toxicity of the carrier. • Avoidance of organic solvents. • Incorporation of lipophilic and hydrophilic drugs. Preparation of solid lipid nanoparticles SLNs are prepared from lipid, emulsifier and water/solvent by using different methods Aim to solid lipid nanoparticle

6. A. Hot homogenization B. Cold homogenization 2 . Ultrasonication /high speed homogenization A. Probe ultrasonication B. Bath ultrasonication 3. Solvent evaporation method 4 . Solvent emulsification-diffusion method 5.Supercritical fluid method 6. Microemulsion based method 7 . Spray drying method 8. Double emulsion method 9. Precipitation technique 10 . Film-ultrasound dispersion 1 . High pressure homogenization

7. LIPID MATRIX - B eeswax Behenic acid Caprilic / capric triglyceride Cholesterol Steric acid Solid paraffin EMULSIFIERS - Phosphatidyl choline 95% Soy & Egg lecithin Poloxamer 407,188, Cremophor EL, Polysorbate 80 CO-EMULSIFIER Tyloxopol , Butanol , Sodium oleate CRYOPROTECTANTS Trehalose , Glucose,Mannose ,   EXCIPIENT USED IN SOLID LIPID NANOPARTICLE

8. 1.PARTICLE SIZE- 2. Influence of the ingredients on product quality 3.Influence of the lipids 4.Influence of the emulsifiers APPLICATION OF SLN . 1.SLN as potential new adjuvant for vaccines 2. Solid lipid nanoparticles in cancer chemotherapy 3.Solid lipid nanoparticles for delivering peptides and proteins PROBLEM ASSOCIATED WITH SOLID LIPID NANOPARTICLE

9. 5. Solid lipid nanoparticles for parasitic diseases 6. Solid lipid nanoparticles for ultrasonic drug and gene delivery 7. SLN applications for improved delivery of antiretroviral drugs to the brain 8. SLN applied to the treatent of malaria 9.Targeted delivery of solid lipid nanoparticles for the treatment of lung disease 10. Solid lipid nanoparticles in tuberculosis disease 4.Solid lipid nanoparticles for targeted brain drug delivery

10. Nanostructured lipid carriers (NLCs) is being explored present a relatively new type of colloidal drug delivery system that consists of solid lipid and liquid lipid, and offers the advantage of improved drug loading capacity and release properties . NLCs have the usual particle diameter ranging 10–1000 nm. 2)NANO STRUCTURE LIPID CARRIER Introduction

11. • Better physical stability • Increased dispersability in an aqueous medium • High entrapment of lipophilic drugs and hydrophilicdrugs • Controlled particle size • An advanced and efficient carrier system in particular for substances • Increase of skin occlusion • Extended release of the drug ADVANTAGES

12. Three Types of Excipients used Nanostructure Lipid Carrier Lipid Water Emulsifier 1.Lipid- Both solid and liquid lipids are included in NLCs for constructing the inner cores. The solid lipids commonly used for NLCs include fatty acids (e.g. stearic acid), triglycerides (e.g. tristearin ), steroids (e.g. cholesterol), and waxes (e.g. cetyl palmitate ) 2.Emulsifiers- The emulsifiers have been used to stabilize the lipid dispersions. Most of the investigations employ hydrophilic emulsifiers such as Pluronic F68 ( poloxamer 188), polysorbates (Tween), polyvinyl alcohol, and sodium deoxycholate . Lipophilic or amphiphilic emulsifiers such as Span 80 EXCIPIENTS USED IN NANO STRUCTURED LIPID CARRIERS(NLC)

13. INGREDIENTS M ATERIALS SOLID LIPID Tristerin,stearic acid , cetyl palmitate , cholesterol, precirol,softisan,geliol LIQUID LIPID Medium chain triglycerides,paraffin oil, 2-octyl dodecanol Oleic acid, squalene , isopropyl myristate , vitamin, HYDROPHILIC EMULSIFIER Pluronic F68 (paloxamer188), tween 20, tween40,tween60, Polyvinyl alcohol, solutol ,, trahalose , sodium deoxycholate , Sodium glycocholate , sodium oleat,polyglycerol methyl distearate . LIPOPHILIC EMULSIFIER Myverol , span 20,40,60 AMPHIPHILIC EMULSIFIER Egg lecithin,soya lecithin, phospatidylcholine , phosphadylethanolamines 3.Water water used in all experiments was purified by reverse osmosis .

14. 1 High pressure homogenization 2. Microemulsion technique 3. Solvent emulsification-evaporation technique 3. Solvent emulsification-evaporation technique 5. Phase inversion temperature (PIT) method 6. Melting dispersion method 7.High Shear Homogenization or Ultrasonication Technique 8.Solvent injection (or solvent displacement) technique METHOD OF PREPARATION NANOSTRUCTURE LIPID CARRIER

15. Oral drug delivery system Topical drug delivery system Parentral drug delivery system Brain drug delivery system Pulmonary drug delivery system Cardiovascular treatment Intranasal drug delivery system Ocular drug delivery system Cancer chemotherapy Parasitic treatment Cosmetic application APPLICATION

16. Phrmaceutical nanosuspension finely colloid biphasic dispersed and solid drug particle in aqueous vehicle size below 1um without any matrix material stabilised surfactant and polymer Advantages of Nanosuspensions Can be applied for the poorly water soluble drugs. Can be given by any route. Reduced tissue irritation in case of subcutaneous/intramuscular administration. Rapid dissolution and tissue targeting can be achieved by IV route of administration. NANOSUSPENSION

17. The absorption from absorption window of the drugs can be increased, due to reduction in the particle size. Higher bioavailability and more consistent dosing in case of ocular administration and inhalation delivery. Drugs with high log P value can be formulated as nanosuspensions to increase the bioavailability of such drugs. Improvement in biological performance due to high dissolution rate and saturation solubility of the drug. Ease of manufacture and little batch-to-batch variation. Long term physical stability (Due to absence of Ostwald ripening). Nanosuspensions can be incorporated in tablets, pellets, hydrogel and suppositories are suitable for various routes of administration. Increasing the amorphous fraction in the particles, leading to a potential change in the crystalline structure and higher solubility. Possibility of surface-modification of nanosuspension for site specific delivery Oral administration of nanosuspensions provide rapid onset, reduced fed/fasted ratio and improved bioavailability .

18.  Physical stability, sedimentation and compaction can causes problems.  It is bulky sufficient care must be taken during handling and transport.  Uniform and accurate dose cannot be achieved unless suspension are in proper dose PREPARATION OF NANOSUSPENSIONS 1)High pressure homogenization 2) Homogenisation in nonaqueous media ( nanopure ) 3) Nanoedge 4)Lipid emulsion/ microemulsion template 5)Media milling disadvantages

19. 1)Stabilizer – Cellulosics , Poloxamers , Polysorbates , Lecithin and Povidones . 2)Organic solvents- Partially water-miscible organic solvents like glycols can be used as the internal phase of the microemulsion when the nanosuspensions are to be produced using a microemulsion as a template. 3)Surfactants - Surfactants are incorporated to improve the dispersion by reducing the interfacial tension. They also act as wetting or deflocculating agents e.g. Tweens and Spans - widely used surfactants . 4)Co-surfactants- Transcutol , glycofurol , ethanol and iso -propanol EXCEPIENTS USED IN NANOSUSPENSION

20. 1)Oral Drug Delivery : 2) Parentral Drug Delivery: 3)Pulmonary Drug Delivery 4) Occular Drug Delivery 5)Targeted Drug Delivery 6 ) Mucoadhesion Of Nanoparticle APPLICATIONS