Download as PDF, PPTX
More Related Content
Nano tech
- 1. The Scope andChallenges of Nanotechnology Application in Solid Oral Dosage Forms Ruchir Shah Manager, Formulation Development Intas Pharmaceuticals Pvt Ltd
- 2. What is Nano-Technology? •Definition • Terminology is very broad • No internationally accepted definition/nomenclature • General Consideration • Umbrella term used to define the products, processes and properties at the nano/sub-micron scale (1-1000 nm) “Nanotechnology is science, engineering, and technology conducted at the nanoscale, which is about 1 to 1000 nanometers which produces systems/material with at least one novel/superior characteristic or property.”
- 3.
- 4. Nano-Pharmaceutical Technology Ø Thereare two types of Nanopharmaceuticals: o Those where the therapeutic molecules are themselves the nanoparticles (i.e., the therapeutic compound itself also functions as its own carrier); and o Those where the therapeutic molecules are directly coupled (functionalized, entrapped, or coated) to a nanoparticle carrier.
- 5. Why Nano DrugDelivery? Parameter Traditional Nano Targeted Delivery Drugs pass through unaffected sites before reaching affected site Able to target on affected area Dosing Frequency High - as loss of drug before it reaches systemic circulation, less BA Reduced due to improved BA Dose High – to produces desired effect Less – to achieve same effect Side Effects More due to higher dose and frequency and unwanted exposure to unaffected area Less Improved safety and Efficacy
- 6. Why Nano DrugDelivery? • In the pharmaceutical sciences, nanotechnology has several advantages, including o Increasing the apparent solubility and dissolution rate of a drug in relation to in vivo bioavailability enhancement o Protection of encapsulated or absorbed therapeutic agents from the external environment o Controlled release of properties o Increasing resistance time in the body (increasing half life for clearance/increasing specificity for its cognate receptors o Targeting drug to specific location in the body (its site of action). o This results in concomitant reduction in quantity of the drug required and dosage toxicity.
- 7. Why Nano DrugDelivery? Commercial Aspect!! Nanopharmaceutical Market is expected to grow by 15% as per BCC report
- 8. Why Nano DrugDelivery? Commercial Aspect!! …2
- 9. Nanotechnology In Solid OralDosage Form
- 10. Oral Administration • Advantages •Patient: Convenience, not invasive, higher compliance, Does not need assistance • Manufacture: well established processes, available infrastructure • More Economical • Disadvantages • Unconscious patients cannot take dose • Low solubility • Low permeability • Degradation by GI enzymes or flora • First pass metabolism • Food interactions • Irregular absorption Majority patient prefer oral route over other injectable routes
- 11. Barriers to OralDrug Delivery • Molecule Size – (Small < 1000 da, large > 5000 da) • Physiological factors of GI tract • pH of GI tract • Diffusion through membrane • Pre-systemic Metabolism • Physicochemical properties • Solubility • Permeability Coefficient • pKa • Dissolution Rate • Stability in GI Environment • Dosage Form Leads to Poor BA
- 12. How Nano Technologycan Help? • Approaches to protect from Harsh GI Tract • Liposomes • Emulsions • Solid Lipid Nanoparticles (SLN) • Polymeric Nanoparticles • Approaches to overcome Mucous Barrier • Muco-adhesive Nanoparticles • Mucous penetrating nanoparticles Overcoming Physiological factors with Nanotechnology
- 13. Approaches to overcomephysicochemical barrier • Nanocrystals • Polymeric Nanoparticles • Dendrimers • Nano-suspensions/Emulsions • Self Nanoemulsifying DDS • Liposomes • Micells • Proliposomes How Nano Technology can Help? Continue…2
- 14. Choice of FormulationNano Technology As per recent report 70 - 90 % drug fall under BCS Class II/IV
- 15. Current FDA ApprovedProduct Landscape
- 16. Nanocrystals • Reducing Particlesize:- • Increase of In-vivo dissolution velocity by surface area enlargement • Increase in saturation solubility • Increase in Bioavailability
- 17. Preparation of Nanocrystals 1.Reduction (Top-down) • High pressure Homogenization • Wet Bead Milling 2. Controlled particle precipitation (Bottom-up) • Spray Drying • Freeze Drying • Anti-solvent
- 18. Equipment's for NanoCrystals 1.Homogenizer 2.UltraSonicator 3.Mills 4.Spray Milling – wet milling 5.Supercritical Fluid Technology 6.Electrospray 7.Ultracentrifugation 8.Nanofiltration
- 19.
- 20. NCD Recirculation Vessel API Stabilizer WFI CWI CWO CWI CWO CWI CWO Recirculation Pump Motor Mechanical Seal WFI Seal Coolant Reservoir PolyMill-500 PolystyreneMilling Media Dynamic Media Separator Screen Agitator Milling Chamber Preparation of Nanoparticles by Wet Milling
- 21. Case Study –Tricor (Fenofibrate) Tablet Marketed By Abbott Therapeutic category Hypercholesterolemia Limitation of earlier Therapy Must be taken with food Technology Nanocrytal Mfg Method Top-down, media milling Solubility Highly Lipophilic in nature and practically insoluble in water Advantage Dose reduction - 145 mg from 160 mg Can be taken with or without Meal unlike earlier Fenofibrate Microcrystals which has to be taken only with Meal Produces same effect at 10% Lower dose Increases Absorption in FED condition by 35%
- 22. Case Study –Tricor (Fenofibrate) Tablet Mean plasma concentration of fenofibric acid after administration of one 160-mg fenofibrate tablet in low- fat fed (n=36) and fasting (n=36) conditions. Mean plasma concentration of fenofibric acid after a single administration of one 145-mg fenofibrate tablet in low-fat fed and fasting conditions (n=44). *The two regimens high-fat fed and fasting were found to be bioequivalent, as were the two regimens low-fat fed and fasting2
- 23. Case Study –Emend (Aprepitant) Tablet Marketed By Merck Therapeutic category Treatment of Emesis Limitations of earlier therapy Higher Dose and Efficacy Concern – Narrow therapeutic window Mfg Method Nanocrystal - Top-down, media milling Solubility Highly Lipophilic in nature and practically insoluble in water Drug Loading ~ 30% Pharmaco-kinetic Narrow Absorption window – Only get absorbed in Upper GI tract Advantage Increased surface area leading to fast dissolution Invivo, Rapid absorption and increased BA and Efficacy Time (min) Plasmaconcentration (mg/mL) Unsuccessful therapy Successful therapy
- 24. Case Study –Rapamune (Sirolimus) Tablet 1mg/2mg Marketed By Wyeth Therapeutic category Immunosupressant Limitations of earlier therapy Available only as suspension due to poor BA in solid form Technology Nanocrytal Mfg Method Top-down, media milling Solubility Highly Lipophilic in nature and practically insoluble in water Drug Loading < 1% Advantage Improved patient compliance with increase in BA of 21% compared to suspension
- 25. In-vivo Effect ofNanocrystal
- 26. Other Nanotechnologies forOral Drug Delivery Nano- Systems Schematic Diagram Example of Composition Method to increase drug solubility
- 27. Challenges …1 • Accordingto the Pharmaceutical Research Manufacturers of America (PhRMA), the average total cost to push a new drug through development in the United States is more than $800 million. • The process takes an average of 12 to 15 years, leaving only five to eight years of U.S. patent protection. PhRMA further notes that just one in 5,000 new compounds survives the process to become a new drug in the marketplace.
- 28. • Characterisation • SolidState Form • Particle Size • Particle Morphology • Drug Delivery • Surface Property • How particles are presented to Host, Cells? • Soluble Vs Insoluble • Organic Vs Inorganic • How to quantify drug in Tissues? • How to determine short and long term stability in various environments? • How are the characterization and Mfg process assessed for targeted delivery? Challenges …2
- 29. • Safety • Asparticle size gets smaller there may me a size specific effect on activity, like • Will nanoparticle get access to tissue and cell, which normally be bypassed by larger particles? • Once they enter tissue, how long they remain there? • How are they metabolised and excreted? • There might be different effects in different cell types? • Route specific issue • For Oral – Increased BA • ADME profile of nano vs larger sized particles • Are current method of determining ADME efficient? • Can nanoparticles can be successfully labelled for ADME studies? Challenges …3
- 30. • Environmental Challenges •Can naoparticles be released in to environment after animal or human use? • What might be the environmental impact on other species? • Like – animals, fish, plants, microorganisms? • Limited scientific data available to address public health issues Challenges …4
- 31. Conclusion • Promising fordelivery of poorly soluble drugs by improving solubility and Bioavailability • Targeting capability – breakthrough for cancer treatment • Classic lifecycle management option for drug companies • Opens up opportunity in smart drug delivery systems • Active Targeting • Passive Targeting • Also need to find new processes(e.g. new nonmanufacturing process) that produce nanoparticles cheaply and in large quantities (Invention > Innovation > Commercialisation)