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Pharm (Pharmaceutics) 1 TOPICS COVERED : TOPICS COVERED Introduction Concept of pulsatile drug delivery Mechanisms of drug release Chronopharmaceutics Global market Future prospects References 2 INTRODUCTION : INTRODUCTION Drug delivery systems – a field of increase in advancement of the technologies . New drug discovery mantra: Development of more efficacious drug delivery systems with already existing molecule. 3 Slide 4: 1st generation drug delivery goal: Getting a simple chemical absorbed predictably from the gut or from the site of injection. 2nd generation drug delivery goal: The perfection of continuous, constant rate delivery of bioactive agents. 3rd generation drug delivery goal: There are predictable resonating dynamic systems, which require different amounts of drug at predictably different times within the circadian cycle which will maximize desired and minimize undesired drug effects. 4 Slide 5: Emergence of the concept of chronopharmaceutics : Research is devoted to the design and evaluation of drug delivery systems that release a therapeutic agent at a rhythm that ideally matches the biological requirement of a given disease therapy. Diseases where constant drug levels are not preferred, but need a pulse of therapeutic concentration in a periodic manner, act as a push for the development of “pulsatile drug delivery systems”. In these systems, there is rapid and transient release of a certain amount of drug molecules within a short time-period immediately after a predetermined off-release period. 5 COMPARISON : COMPARISON Zero order release Pulsatile release Loading sustained release 6 DEFINITION : DEFINITION Pulsatile drug delivery system is defined as the rapid and transient release of certain amount of molecules within a short time period immediately after a predetermined off-release period, i.e., lag time . (A) ideal sigmoidal curve; (B), (C) delayed release after initial lag time 7 NEED FOR PULSATILE DELIVERY : NEED FOR PULSATILE DELIVERY To administer the drug in the right amount, at a proper rate and at the right time. Improved therapeutic efficacy Drug is subjected to large metabolic degradation: Sustained release Greater first pass effect Greater degradation Reduced bioavailability 8 Slide 9: Patients with chronic disorders: Chronic treatment Sustained release dosage form Continuous exposure Adverse effects For chronotherapeutic disorders . To ably administer two different drugs at the same time, yet released at different sites in the GI tract. 9 Slide 10: Drugs with short half life: short half life repetitive dosing Patient non-compliance Drugs exhibiting tolerance: high probability of occurrence of tolerance phenomenon. Drug toxicity increases with time when drug levels are held constant. Offers temporal and/or spatial control over the release of drug. 10 CONCEPT OF PULSATILE DRUG DELIVERY : CONCEPT OF PULSATILE DRUG DELIVERY Characterized by a time period of no release (lag time) followed by a rapid and complete drug release. Drug release profiles: (a) pulsatile, (b) and (c) conventional extended release Feature: A programmed drug release pattern i.e. at appropriate time and/or at appropriate site of action. Designed according to the circadian rhythm of the body. Principle rationale: for the drugs where a constant drug release, i.e., A zero-order release is not desired. 11 Slide 12: Recommended for: Drugs having specific absorption site. Drugs acting only during specific time periods. Drugs undergoing degradation in gastric acidic medium : irritate the gastric mucosa, induce nausea and vomiting. Drug targetting to distal organs of gastro-intestinal tract. Drugs characterized by idiosyncratic pharmacokinetics. Drugs characterised by idiosyncratic pharmacodynamics resulting in: Reduced bioavailability, Altered drug/metabolite ratios, Altered steady state levels of drug and metabolite, And potential food-drug interactions require delayed release of the drug to the extent possible. 12 CURRENTLY REPORTED PULSATILE DRUG DELIVERY SYSTEMS : CURRENTLY REPORTED PULSATILE DRUG DELIVERY SYSTEMS Site specific time controlled single unit multiple unit 13 TYPES OF PULSATILE DRUG DELIVERY SYSTEMS : TYPES OF PULSATILE DRUG DELIVERY SYSTEMS SITE SPECIFIC The drug is released at the desired site within the intestinal tract (e.g., the colon). Site-controlled release is usually controlled by environmental factors, like the pH or enzymes present in the intestinal tract. TIME CONTROLLED The drug is released after a well-defined time period. The drug release from time-controlled systems is controlled primarily by the delivery system and, ideally, not by the environment. 14 Slide 15: SINGLE-UNIT SYSTEMS (eg, tablet or capsule) Capsular Systems Capsular system based on osmosis A System Based on Expandable orifice A system based on delivery by a series of stops Pulsatile Delivery by Solubility Modulation Pulsatile System With Erodible or Soluble Barrier Coatings Multilayered Tablet Pulsatile System With Rupturable Coatings 15 Slide 16: MULTIPARTICULATE SYSTEMS (eg, pellets) Pulsatile System Based on Rupturable Coating Time-Controlled Explosion System Osmotic-Based Rupturable Coating Systems Permeability Controlled System Pulsatile Delivery by Change in Membrane Permeability Sigmoidal Release System 16 MECHANISMS OF DRUG RELEASE : MECHANISMS OF DRUG RELEASE Desorption of surface-bound /adsorbed drugs . Diffusion through carrier matrix. Diffusion through the carrier wall. Carrier matrix erosion. Stimuli induced . Enzyme controlled. Magnetic field and ultrasound. A combined erosion /diffusion process. 17 Slide 18: Pulsatile system based on capsule: Insoluble capsule body + swellable and degradable hydrophilic polymers Swellable hydrogel plug seals the drug contents into capsule body. Lag time controlled by plug . MECHANISM: Capsule in contact with dissolution fluid Plug pushed away by swelling or erosion Drug is released as a pulse 18 Slide 19: Pulsatile system based on osmosis: capsule coated with the semipermiable membrane. Inside the capsule insoluble plug, osmotically active agent the drug formulation MECHANISM: Capsule+ body fluid, the semipermeable membrane allows entry of water pressure develops the insoluble plug expelled due to pressure after some lag time. 19 Slide 20: Systems with eroding, soluble or rupturable barrier coating: Reservoir devices coated with a barrier layer Barrier dissolves/erodes after a specified lag period Drug is released rapidly from the reservoir core lag time Controlled by the thickness of the coating layer 20 Slide 21: Pulsatile system based on change in membrane permeability: Sigmoidal release type of pattern is obtained. MECHANISM: pellet cores having drug + succinic acid coated with ammonio-methacrylate copolymer. water in the medium dissolves succinic acid. drug inside and the acid solution increase the permeability of the polymer film. 21 Slide 22: Pulsatile system of multiparticulates: Number of pellets two/more particle populations Each pellet a core that contains the therapeutic drug a water-soluble osmotic agent. Water permeable Water-insoluble polymer encloses the core A hydrophobic Water-insoluble polymer Mechanism: The osmotic agent dissolves in water, Causes the pellets to swell regulates the rate of diffusion of the drug from the dosage form. 22 POLYMER COATINGS : POLYMER COATINGS Intermittent drug delivery is desired. Simplest pulsatile formulation: two layer press coated tablet consisting of polymers with different dissolution rates. This coating is a hydrophobic-surfactant layer to which a water-soluble polymer is added to improve adhesion to the core. 23 Slide 24: Usual polymer: Hydrophilic Polymer - Hydroxy Propyl Methyl Cellulose (HPMC). Viscosity grade of HPMC Lag time onset of action MECHANISM: Hydrophobic surfactant layer + water-soluble polymer = improves adhesion to the core when in contact with fluid dissolution dispersion rehydrates and redisperses Ethyl cellulose is also used. 24 DRUG CARRIERS : DRUG CARRIERS 25 MECHANISM OF WORKING OF CARRIERS : MECHANISM OF WORKING OF CARRIERS Micelles: Drug physically entrapped micelle core hydrophilic blocks + aqueous surroundings hydrogen bonds tight shell around the micellar core. contents protected against hydrolysis and enzymatic degradation. 26 Slide 27: Liposomes: phospholipid layers Amphiphilic , lipophilic molecules solubilized phospholipid bilayer Niosomes : nonionic surfactants instead of phospholipid bilayer. effective protection from premature degradation by proteolytic enzymes. 27 Slide 28: Dendrimers : nanometer-sized, highly branched and monodisperse macromolecules with symmetrical architecture. Composition central core terminal function groups branching units the environment of nanocavities ; solubilizing properties solubility ; chemical behaviour of polymers 28 Slide 29: Liquid crystals (Combined properties) Solid state Liquid state Can form : Different geometries, with alternative polar and non-polar layers (i.e., a lamellar phase) . Aqueous drug solutions can be included. 29 Slide 30: Nanoparticles: (nanospheres + nanocapsules) (size:10-200 nm) Solid State Amorphous Crystalline Adsorb/encapsulate a drug. Protecting it against chemical and enzymatic degradation. 30 Slide 31: Hydrogels: Three-dimensional, hydrophilic, polymeric networks. Hydrogels exhibit thermodynamic compatibility with water swelling in aqueous media. Hydrogels enviro-intelligent stimuli-sensitive gel systems Modulate release in response to pH, temperature, ionic strength, electric field, or specific analyte concentration differences. 31 CHRONOPHARMACEUTICS : CHRONOPHARMACEUTICS Chronopharmaceutics Chronobiology Pharmaceutics Definition: is a branch of pharmaceutics devoted to the design and evaluation of drug delivery systems that release a bioactive agent at a rhythm that ideally matches the biological requirement of a given disease therapy. 32 THE HUMAN CIRCADIAN CYCLE : THE HUMAN CIRCADIAN CYCLE 33 CHRONOPHARMACOTHERAPY : CHRONOPHARMACOTHERAPY Chronopharmacotherapy : therapy for diseases which show circadian rhythms in their pathophysiology. Chronobiology is the study of biological rhythms and their mechanisms. There are three types of mechanical rhythms in our body. Circadian: This word comes from Latin word `circa’ means `about ‘ and `dies’ means `day’. Ultrdian: Oscillation of shorter duration are termed as ultradian (more than one cycle per 24 hours). Infradian: Oscillations that are longer than 24 hours (less than one cycle per day). 34 APPLICATION TO DISEASES : APPLICATION TO DISEASES 35 ADVANTAGES OF PULSATILE DRUG DELIVERY SYSTEMS : ADVANTAGES OF PULSATILE DRUG DELIVERY SYSTEMS Usual advantages of oral route of drug administration. Maintains the drug in the desired therapeutic range by a single administration. Localized delivery of the drug to a particular body compartment. Lowering the systemic drug level. Preservation of medications that are rapidly destroyed by the body. Time lag can be determined previously by the manufacturer. Mimics the way by which the body naturally produces hormones . 36 Slide 37: Offer temporal and/or spatial control over the release of drug. Grant a new lease on life to a drug molecule in terms of patentability. Prevention of peak-valley fluctuations. Reduction in dose of drug. Reduced dosage frequency. Avoidance of side effects. Usage of drug-carrying polymers that respond to specific stimuli (e.G., Exposure to light, changes in ph or temperature). Improved patient compliance. 37 DISADVANTAGES : DISADVANTAGES Homogenicity of the coated barrier is mandatory to assure the predictability of the lag time. Rupture time cannot be always adequately manipulated as it depends on the physicochemical properties of the polymer. Pulsatile delivery drugs are costly. Raw material is not easily available. Dosage form design requires highly educated professionals. Technologies employed and the equipments used are complicated. 38 PATENTED TECHNOLOGIES : PATENTED TECHNOLOGIES Elan Drug TechnologiesSODAS® TechnologyMultiparticulate delivery system, providing tailored, highly flexible release profiles including controlled release, immediate release and pulsatile release of drugIPDAS® Technology Controlled release tablet technology, designed for use with more gastrointestinal irritant compounds.CODAS® Technology Technology for tailored release of drug to allow chronotherapeutic delivery.PRODAS™ Technology Multiparticulate minitab technology system, that combines the benefits of tabletting technology within a capsule. MXDAS® Technology Hydrophilic matrix technology which controls the release of drug through a process of diffusion and erosion in the gastrointestinal tract. DUREDAS® Technology Bilayer tablet which can provide immediate or sustained release of two drugs or different release rates of the same drug in one dosage form. 39 Slide 40: EUDRAPULSETM AQUACAOT ® ECD Orbexa® Pulsys® are the other patented technologies , to name a few. Programmable Oral Release Technologies 40 ADVANCED PULSATILE DELIVERY APPARATUS : ADVANCED PULSATILE DELIVERY APPARATUS Pulsatile blood pump for cardiovascular and haemodynamic studies. Pulsatile irrigation apparatus. 41 GLOBAL MARKET : GLOBAL MARKET Drug Delivery Systems:The global market for advanced drug delivery systems was more than 37.9 billion E$ in 2000 and is estimated to grow and reach 75B E$ by 2005. it is growing even tremendously since 2005 onwards. controlled release 19.8B E$ needle-less injection 0.8B E$ injectable/impantable polymer systems 5.4B E$, transdermal 9.6B E$ transnasal 12.0B E$ pulmonary 17.0B E$ rectal 0.9B E$ liposomal drug delivery 2.5B E$ cell/gene therapy 3.8B E$ miscellaneous 1.9B E$. 42 FUTURE DEVELOPMENT : FUTURE DEVELOPMENT During the last two decades, technologies to ensure time-controlled pulsatile release of bioactive compounds have been developed. Significant progress has been made towards achieving pulsatile drug delivery systems that can effectively treat diseases with non-constant dosing therapies, such as diabetes. However, there is much work that needs to be carefully demonstrated for the pulsatile delivery of bioactive compounds, especially hormones. Developments within this market are continuing at a rapid pace, especially in the area of alternatives to injected macromolecules, as drug formulations seek to cash in on the 6.2B E$ worldwide market for genetically engineered protein and peptide drugs and other biological therapeutics 43 Slide 44: Creating novel drug delivery systems will help us, PHARMACISTS, keep alive …. the PULSE OF LIFE !!! 44 REFERENCES : REFERENCES Indian Journal Of Pharmaceutical Sciences www.google.com ( accessed on 28-08-09) www.biomed.metu.edu.tr (accessed on 29-08-09 ) http://www.freepatentsonline.com (accessed on 29-08-09) http://www.ingentaconnect.com (accessed on 30-08-09) http://www.niper.ac.in (accessed on 30-08-09) www.pharmainfo.net (accessed on 1-09-09) http://www.drugdeliverytech.com (accessed on 1-08-09) www.elandrugtechnologies.com (accessed on 1-08-09) www.eurand.com (accessed n 1-08-09) www.nanost.net (accessed on 2-08-09) 45 ACKNOWLEDGEMENT : ACKNOWLEDGEMENT Respected Principal, Dr. B.S.Kuchekar for his support. Prof. S.A. Polshettiwar for his able guidance. 46 Thank you ! : Thank you ! 47 You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
rujuta pharmapresentation Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 1601 Category: Entertainment License: All Rights Reserved Like it (5) Dislike it (0) Added: September 11, 2009 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: patildd (14 month(s) ago) sir/ madam i am M. pharm student at grace college of pharmacy, palakkad, kerala, i want download that ppt otherwise plz send me this my email id - dinesh.patil.24@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close By: kcmathuria (18 month(s) ago) good presentation,plz send me this ppt my email id kcmathuria1985@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close By: porabhai (21 month(s) ago) hello mam ur presentation is excellent.....can you send ur power point presentation to me...my mail ID: ishkumarsat@yahoo.co.in Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript CONTROLLED DRUG DELIVERY SYSTEMS… CURRENT SCENARIO IN PULSATILE DRUG DELIVERY SYSTEM : CONTROLLED DRUG DELIVERY SYSTEMS… CURRENT SCENARIO IN PULSATILE DRUG DELIVERY SYSTEM By RUJUTA SANJAY MEHENDALE T.Y.B.Pharm MAEER’S Maharashtra Institute Of Pharmacy, Pune, INDIA. Guide: Prof. S.A.Polshettiwar M. Pharm (Pharmaceutics) 1 TOPICS COVERED : TOPICS COVERED Introduction Concept of pulsatile drug delivery Mechanisms of drug release Chronopharmaceutics Global market Future prospects References 2 INTRODUCTION : INTRODUCTION Drug delivery systems – a field of increase in advancement of the technologies . New drug discovery mantra: Development of more efficacious drug delivery systems with already existing molecule. 3 Slide 4: 1st generation drug delivery goal: Getting a simple chemical absorbed predictably from the gut or from the site of injection. 2nd generation drug delivery goal: The perfection of continuous, constant rate delivery of bioactive agents. 3rd generation drug delivery goal: There are predictable resonating dynamic systems, which require different amounts of drug at predictably different times within the circadian cycle which will maximize desired and minimize undesired drug effects. 4 Slide 5: Emergence of the concept of chronopharmaceutics : Research is devoted to the design and evaluation of drug delivery systems that release a therapeutic agent at a rhythm that ideally matches the biological requirement of a given disease therapy. Diseases where constant drug levels are not preferred, but need a pulse of therapeutic concentration in a periodic manner, act as a push for the development of “pulsatile drug delivery systems”. In these systems, there is rapid and transient release of a certain amount of drug molecules within a short time-period immediately after a predetermined off-release period. 5 COMPARISON : COMPARISON Zero order release Pulsatile release Loading sustained release 6 DEFINITION : DEFINITION Pulsatile drug delivery system is defined as the rapid and transient release of certain amount of molecules within a short time period immediately after a predetermined off-release period, i.e., lag time . (A) ideal sigmoidal curve; (B), (C) delayed release after initial lag time 7 NEED FOR PULSATILE DELIVERY : NEED FOR PULSATILE DELIVERY To administer the drug in the right amount, at a proper rate and at the right time. Improved therapeutic efficacy Drug is subjected to large metabolic degradation: Sustained release Greater first pass effect Greater degradation Reduced bioavailability 8 Slide 9: Patients with chronic disorders: Chronic treatment Sustained release dosage form Continuous exposure Adverse effects For chronotherapeutic disorders . To ably administer two different drugs at the same time, yet released at different sites in the GI tract. 9 Slide 10: Drugs with short half life: short half life repetitive dosing Patient non-compliance Drugs exhibiting tolerance: high probability of occurrence of tolerance phenomenon. Drug toxicity increases with time when drug levels are held constant. Offers temporal and/or spatial control over the release of drug. 10 CONCEPT OF PULSATILE DRUG DELIVERY : CONCEPT OF PULSATILE DRUG DELIVERY Characterized by a time period of no release (lag time) followed by a rapid and complete drug release. Drug release profiles: (a) pulsatile, (b) and (c) conventional extended release Feature: A programmed drug release pattern i.e. at appropriate time and/or at appropriate site of action. Designed according to the circadian rhythm of the body. Principle rationale: for the drugs where a constant drug release, i.e., A zero-order release is not desired. 11 Slide 12: Recommended for: Drugs having specific absorption site. Drugs acting only during specific time periods. Drugs undergoing degradation in gastric acidic medium : irritate the gastric mucosa, induce nausea and vomiting. Drug targetting to distal organs of gastro-intestinal tract. Drugs characterized by idiosyncratic pharmacokinetics. Drugs characterised by idiosyncratic pharmacodynamics resulting in: Reduced bioavailability, Altered drug/metabolite ratios, Altered steady state levels of drug and metabolite, And potential food-drug interactions require delayed release of the drug to the extent possible. 12 CURRENTLY REPORTED PULSATILE DRUG DELIVERY SYSTEMS : CURRENTLY REPORTED PULSATILE DRUG DELIVERY SYSTEMS Site specific time controlled single unit multiple unit 13 TYPES OF PULSATILE DRUG DELIVERY SYSTEMS : TYPES OF PULSATILE DRUG DELIVERY SYSTEMS SITE SPECIFIC The drug is released at the desired site within the intestinal tract (e.g., the colon). Site-controlled release is usually controlled by environmental factors, like the pH or enzymes present in the intestinal tract. TIME CONTROLLED The drug is released after a well-defined time period. The drug release from time-controlled systems is controlled primarily by the delivery system and, ideally, not by the environment. 14 Slide 15: SINGLE-UNIT SYSTEMS (eg, tablet or capsule) Capsular Systems Capsular system based on osmosis A System Based on Expandable orifice A system based on delivery by a series of stops Pulsatile Delivery by Solubility Modulation Pulsatile System With Erodible or Soluble Barrier Coatings Multilayered Tablet Pulsatile System With Rupturable Coatings 15 Slide 16: MULTIPARTICULATE SYSTEMS (eg, pellets) Pulsatile System Based on Rupturable Coating Time-Controlled Explosion System Osmotic-Based Rupturable Coating Systems Permeability Controlled System Pulsatile Delivery by Change in Membrane Permeability Sigmoidal Release System 16 MECHANISMS OF DRUG RELEASE : MECHANISMS OF DRUG RELEASE Desorption of surface-bound /adsorbed drugs . Diffusion through carrier matrix. Diffusion through the carrier wall. Carrier matrix erosion. Stimuli induced . Enzyme controlled. Magnetic field and ultrasound. A combined erosion /diffusion process. 17 Slide 18: Pulsatile system based on capsule: Insoluble capsule body + swellable and degradable hydrophilic polymers Swellable hydrogel plug seals the drug contents into capsule body. Lag time controlled by plug . MECHANISM: Capsule in contact with dissolution fluid Plug pushed away by swelling or erosion Drug is released as a pulse 18 Slide 19: Pulsatile system based on osmosis: capsule coated with the semipermiable membrane. Inside the capsule insoluble plug, osmotically active agent the drug formulation MECHANISM: Capsule+ body fluid, the semipermeable membrane allows entry of water pressure develops the insoluble plug expelled due to pressure after some lag time. 19 Slide 20: Systems with eroding, soluble or rupturable barrier coating: Reservoir devices coated with a barrier layer Barrier dissolves/erodes after a specified lag period Drug is released rapidly from the reservoir core lag time Controlled by the thickness of the coating layer 20 Slide 21: Pulsatile system based on change in membrane permeability: Sigmoidal release type of pattern is obtained. MECHANISM: pellet cores having drug + succinic acid coated with ammonio-methacrylate copolymer. water in the medium dissolves succinic acid. drug inside and the acid solution increase the permeability of the polymer film. 21 Slide 22: Pulsatile system of multiparticulates: Number of pellets two/more particle populations Each pellet a core that contains the therapeutic drug a water-soluble osmotic agent. Water permeable Water-insoluble polymer encloses the core A hydrophobic Water-insoluble polymer Mechanism: The osmotic agent dissolves in water, Causes the pellets to swell regulates the rate of diffusion of the drug from the dosage form. 22 POLYMER COATINGS : POLYMER COATINGS Intermittent drug delivery is desired. Simplest pulsatile formulation: two layer press coated tablet consisting of polymers with different dissolution rates. This coating is a hydrophobic-surfactant layer to which a water-soluble polymer is added to improve adhesion to the core. 23 Slide 24: Usual polymer: Hydrophilic Polymer - Hydroxy Propyl Methyl Cellulose (HPMC). Viscosity grade of HPMC Lag time onset of action MECHANISM: Hydrophobic surfactant layer + water-soluble polymer = improves adhesion to the core when in contact with fluid dissolution dispersion rehydrates and redisperses Ethyl cellulose is also used. 24 DRUG CARRIERS : DRUG CARRIERS 25 MECHANISM OF WORKING OF CARRIERS : MECHANISM OF WORKING OF CARRIERS Micelles: Drug physically entrapped micelle core hydrophilic blocks + aqueous surroundings hydrogen bonds tight shell around the micellar core. contents protected against hydrolysis and enzymatic degradation. 26 Slide 27: Liposomes: phospholipid layers Amphiphilic , lipophilic molecules solubilized phospholipid bilayer Niosomes : nonionic surfactants instead of phospholipid bilayer. effective protection from premature degradation by proteolytic enzymes. 27 Slide 28: Dendrimers : nanometer-sized, highly branched and monodisperse macromolecules with symmetrical architecture. Composition central core terminal function groups branching units the environment of nanocavities ; solubilizing properties solubility ; chemical behaviour of polymers 28 Slide 29: Liquid crystals (Combined properties) Solid state Liquid state Can form : Different geometries, with alternative polar and non-polar layers (i.e., a lamellar phase) . Aqueous drug solutions can be included. 29 Slide 30: Nanoparticles: (nanospheres + nanocapsules) (size:10-200 nm) Solid State Amorphous Crystalline Adsorb/encapsulate a drug. Protecting it against chemical and enzymatic degradation. 30 Slide 31: Hydrogels: Three-dimensional, hydrophilic, polymeric networks. Hydrogels exhibit thermodynamic compatibility with water swelling in aqueous media. Hydrogels enviro-intelligent stimuli-sensitive gel systems Modulate release in response to pH, temperature, ionic strength, electric field, or specific analyte concentration differences. 31 CHRONOPHARMACEUTICS : CHRONOPHARMACEUTICS Chronopharmaceutics Chronobiology Pharmaceutics Definition: is a branch of pharmaceutics devoted to the design and evaluation of drug delivery systems that release a bioactive agent at a rhythm that ideally matches the biological requirement of a given disease therapy. 32 THE HUMAN CIRCADIAN CYCLE : THE HUMAN CIRCADIAN CYCLE 33 CHRONOPHARMACOTHERAPY : CHRONOPHARMACOTHERAPY Chronopharmacotherapy : therapy for diseases which show circadian rhythms in their pathophysiology. Chronobiology is the study of biological rhythms and their mechanisms. There are three types of mechanical rhythms in our body. Circadian: This word comes from Latin word `circa’ means `about ‘ and `dies’ means `day’. Ultrdian: Oscillation of shorter duration are termed as ultradian (more than one cycle per 24 hours). Infradian: Oscillations that are longer than 24 hours (less than one cycle per day). 34 APPLICATION TO DISEASES : APPLICATION TO DISEASES 35 ADVANTAGES OF PULSATILE DRUG DELIVERY SYSTEMS : ADVANTAGES OF PULSATILE DRUG DELIVERY SYSTEMS Usual advantages of oral route of drug administration. Maintains the drug in the desired therapeutic range by a single administration. Localized delivery of the drug to a particular body compartment. Lowering the systemic drug level. Preservation of medications that are rapidly destroyed by the body. Time lag can be determined previously by the manufacturer. Mimics the way by which the body naturally produces hormones . 36 Slide 37: Offer temporal and/or spatial control over the release of drug. Grant a new lease on life to a drug molecule in terms of patentability. Prevention of peak-valley fluctuations. Reduction in dose of drug. Reduced dosage frequency. Avoidance of side effects. Usage of drug-carrying polymers that respond to specific stimuli (e.G., Exposure to light, changes in ph or temperature). Improved patient compliance. 37 DISADVANTAGES : DISADVANTAGES Homogenicity of the coated barrier is mandatory to assure the predictability of the lag time. Rupture time cannot be always adequately manipulated as it depends on the physicochemical properties of the polymer. Pulsatile delivery drugs are costly. Raw material is not easily available. Dosage form design requires highly educated professionals. Technologies employed and the equipments used are complicated. 38 PATENTED TECHNOLOGIES : PATENTED TECHNOLOGIES Elan Drug TechnologiesSODAS® TechnologyMultiparticulate delivery system, providing tailored, highly flexible release profiles including controlled release, immediate release and pulsatile release of drugIPDAS® Technology Controlled release tablet technology, designed for use with more gastrointestinal irritant compounds.CODAS® Technology Technology for tailored release of drug to allow chronotherapeutic delivery.PRODAS™ Technology Multiparticulate minitab technology system, that combines the benefits of tabletting technology within a capsule. MXDAS® Technology Hydrophilic matrix technology which controls the release of drug through a process of diffusion and erosion in the gastrointestinal tract. DUREDAS® Technology Bilayer tablet which can provide immediate or sustained release of two drugs or different release rates of the same drug in one dosage form. 39 Slide 40: EUDRAPULSETM AQUACAOT ® ECD Orbexa® Pulsys® are the other patented technologies , to name a few. Programmable Oral Release Technologies 40 ADVANCED PULSATILE DELIVERY APPARATUS : ADVANCED PULSATILE DELIVERY APPARATUS Pulsatile blood pump for cardiovascular and haemodynamic studies. Pulsatile irrigation apparatus. 41 GLOBAL MARKET : GLOBAL MARKET Drug Delivery Systems:The global market for advanced drug delivery systems was more than 37.9 billion E$ in 2000 and is estimated to grow and reach 75B E$ by 2005. it is growing even tremendously since 2005 onwards. controlled release 19.8B E$ needle-less injection 0.8B E$ injectable/impantable polymer systems 5.4B E$, transdermal 9.6B E$ transnasal 12.0B E$ pulmonary 17.0B E$ rectal 0.9B E$ liposomal drug delivery 2.5B E$ cell/gene therapy 3.8B E$ miscellaneous 1.9B E$. 42 FUTURE DEVELOPMENT : FUTURE DEVELOPMENT During the last two decades, technologies to ensure time-controlled pulsatile release of bioactive compounds have been developed. Significant progress has been made towards achieving pulsatile drug delivery systems that can effectively treat diseases with non-constant dosing therapies, such as diabetes. However, there is much work that needs to be carefully demonstrated for the pulsatile delivery of bioactive compounds, especially hormones. Developments within this market are continuing at a rapid pace, especially in the area of alternatives to injected macromolecules, as drug formulations seek to cash in on the 6.2B E$ worldwide market for genetically engineered protein and peptide drugs and other biological therapeutics 43 Slide 44: Creating novel drug delivery systems will help us, PHARMACISTS, keep alive …. the PULSE OF LIFE !!! 44 REFERENCES : REFERENCES Indian Journal Of Pharmaceutical Sciences www.google.com ( accessed on 28-08-09) www.biomed.metu.edu.tr (accessed on 29-08-09 ) http://www.freepatentsonline.com (accessed on 29-08-09) http://www.ingentaconnect.com (accessed on 30-08-09) http://www.niper.ac.in (accessed on 30-08-09) www.pharmainfo.net (accessed on 1-09-09) http://www.drugdeliverytech.com (accessed on 1-08-09) www.elandrugtechnologies.com (accessed on 1-08-09) www.eurand.com (accessed n 1-08-09) www.nanost.net (accessed on 2-08-09) 45 ACKNOWLEDGEMENT : ACKNOWLEDGEMENT Respected Principal, Dr. B.S.Kuchekar for his support. Prof. S.A. Polshettiwar for his able guidance. 46 Thank you ! : Thank you ! 47