logging in or signing up Drug release mechanisms and kinetics vamsikrishnareddy 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: 8021 Category: Science & Tech.. License: All Rights Reserved Like it (19) Dislike it (0) Added: October 15, 2009 This Presentation is Public Favorites: 15 Presentation Description it describes the release mechanism of drugslike diffusion,dissolution Comments Posting comment... By: savitashetty (3 week(s) ago) Kindly send this presentation to savitashetty1@rediffmail.com. Thanks a million Saving..... Post Reply Close Saving..... Edit Comment Close By: alizarrabi (7 month(s) ago) Dear Sir, Thank you very much for the presentation. 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Edit Comment Close By: suneethasusan (10 month(s) ago) Hello sir, please mail this ppt to ssc.31.7@gmail.com. thank you in advance Saving..... Post Reply Close Saving..... Edit Comment Close loading.... See all Premium member Presentation Transcript DRUG RELEASE MECHANISM AND KINETICS : 1 DRUG RELEASE MECHANISM AND KINETICS Submitted by B.VamsikrishnaReddy M.Pharm first year, Pharmaceutics, MCOPS, Manipal. Phone:+91-9008418512 vamsikrishnareddy57@gmail.com Slide 2: 2 DRUG DELIVERY SYSTEM :- Drug delivery System will deliver the drug at a rate determined by the needs of the body over a specified period of time. CONTROLLED RELEASE SYSTEM :- Control release is helpful for maintaining constant drug levels in the target tissues or cells. Slide 3: 3 TYPES OF CONTROLLED drug release SYSTEMS:- 1) Dissolution controlled systems a) Encapsulation dissolution controlled system. b) Matrix dissolution controlled systems. 2)Diffusion controlled systems a) Reservoir controlled systems. b) Matrix controlled systems. 3)Dissolution and diffusion controlled release systems Slide 4: 4 4)Water penetration controlled systems a) Swelling controlled systems b) Osmotically controlled systems. 5) Chemically controlled release systems a) erodible systems b) drug covalently linked with polymer 6) Hydro gels 7) Ion - exchange resin controlled release systems DISSOLUTION CONTROLLED SYSTEMS : 5 DISSOLUTION CONTROLLED SYSTEMS In dissolution controlled systems, the rate controlling step is dissolution. the drug is embedment in slowly dissolving or erodible matrix or by coating with slowly dissolving substances. It is of two types and they are Encapsulation dissolution controlled system Matrix dissolution controlled system ENCAPSULATION DISSOLUTION CONTROLLED SYSTEMS :- : 6 ENCAPSULATION DISSOLUTION CONTROLLED SYSTEMS :- The drug particles are coated or encapsulated by microencapsulation techniques with slowly dissolving materials like cellulose, poly ethylene glycols, polymethacrylates, waxes etc. the dissolution rate of coat depends upon the solubility and thickness of the coating. MATRIX DISSOLUTION CONTROLLED SYSTEMS :- : 7 MATRIX DISSOLUTION CONTROLLED SYSTEMS :- Matrix systems are also called as monoliths since the drug is homogeneously dispersed throughout a rate controlling medium. They employ waxes such as beeswax, carnauba wax, hydrogenated castor oil etc which control drug dissolution by controlling the rate of dissolution fluid penetration into the matrix by altering the porosity of rate. The wax embedded drug is generally prepared by dispersing the drug in molten wax and congealing and granulating the same. Slide 8: 8 DIFFUSION CONTROLLED RELEASE SYSTEMS:- : 9 DIFFUSION CONTROLLED RELEASE SYSTEMS:- Diffusion systems are characterized by release rate of drug is dependant on its diffusion through inert water insoluble membrane barrier. There are basically two types of diffusion devices. a) Reservoir diffusion system b) Matrix diffusion system Reservoir diffusion system : 10 Reservoir diffusion system MATRIX DIFFUSION SYSTEMS : 11 MATRIX DIFFUSION SYSTEMS DISSOLUTION AND DIFFUSION CONTROLLED RELEASE SYSTEMS : 12 DISSOLUTION AND DIFFUSION CONTROLLED RELEASE SYSTEMS The drug core is encased in a partially soluble membrane. Pores are thus created due to dissolution of parts of the membrane which Permit entry of aqueous medium into the core and hence drug dissolution occurs Allow diffusion of dissolved drug out of the system. An example of obtaining such a coating is using a mixture of ethyl cellulose with poly vinyl pyrrolidiene or methyl cellulose. Water Penetration Controlled Systems : 13 Water Penetration Controlled Systems In water penetration controlled delivery systems, rate control is obtained by the penetration of water into the system. They are Swelling Controlled Systems:- Swelling controlled release systems are initially dry and when placed in the body absorb water or other body fluids and swell. Swelling increases the aqueous solvent content within the formulation as well as the polymer mesh size, enabling the drug to diffuse through the swollen network into the external environment Slide 14: 14 “a” indicates reservoir diffusion swelling. “b” indicates matrix diffusion swelling. OSMOTICALLY CONTROLLED RELEASE SYSTEMS : 15 OSMOTICALLY CONTROLLED RELEASE SYSTEMS These systems are fabricated by encapsulating an osmotic drug core containing an osmotically active drug (or a combination of an osmotically inactive drug with an osmotically active salt eg NaCl) within a semi permeable membrane made from biocompatible polymer, e.g. cellulose acetate. A gradient of osmotic pressure is they created, under which the drug solutes are continuously pumped out over a prolonged period of time through the delivery orifice. Slide 16: 16 This type of drug system dispenses drug solutes continuously at a zero order rate. CHEMICALLY CONTROLLED RELEASE SYSTEMS : 17 CHEMICALLY CONTROLLED RELEASE SYSTEMS Chemically controlled release systems are the systems that change their chemical structure, when exposed to biological fluid. Mostly, biodegradable polymers are designed to degrade as a result of hydrolysis of the polymer chains into biologically safe and progressively smaller moieties. It is of two types and they are Erodible systems Pendent chain system Erodible systems : 18 Erodible systems In erodible systems, the mechanism of drug release occurs by erosion. Erosion may be two types and they are a) Bulk erosion process b) Surface erosion process Bulk erosion:- polymer degradation may occur through bulk hydrolysis. Surface erosion:- Polymers like polyorthoesters and polyanhydrides etc occurs degradation only at the surface of the polymer, resulting in a release rate that is proportional to the surface area of the delivery system. Slide 19: 19 “a” indicates bulk erosion “b” indicates surface erosion PENDENT CHAIN SYSTEM : 20 PENDENT CHAIN SYSTEM Pendent chain systems consists of linear homo or copolymers with the drug attached to the backbone chains. The drug is released from the polymer by hydrolysis or enzymatic degradation of the linkages. Zero order can be obtained and the cleavage of the drug is the rate controlling mechanism. Example for polymers used in pendent chain systems like n-(2-hydroxy propyl)methacrylamide etc. Hydrogels : 21 Hydrogels Hydrogels are water swollen three dimensional structures composed of primarily hydrophilic polymers. They are rendered insoluble because of chemical or physical cross-links. the physical cross-links include crystallites, entanglements or weak associations like hydrogen bonds or vander waals forces. these cross-links provide the physical integrity and network structure. Hydrogels provide desirable protection of labile drugs, peptides and proteins. Slide 22: 22 Because of their nature , hydrogels can be used in many different types of controlled release systems. These systems are classified according to the mechanism controlling the release of the drug from the device. They are classified as follows a) Diffusion controlled systems b) Swelling-controlled systems c) Chemically controlled systems d) Environmentally responsive systems Example for environmentally responsive systems : 23 Example for environmentally responsive systems . Ion-Exchange resins Controlled RELEASE SYSTEMS : 24 . Ion-Exchange resins Controlled RELEASE SYSTEMS This systems are designed to provide the controlled release of an ionic (or ionizable) drug . It is prepared by first absorbing an ionized drug onto the ion-exchange resin granules such as codeine base with Amberlite , and then after filtration from the alcoholic medium, coating the drug resin complex granules with a water permeable polymer, e.g. a modified copolymer of polyacrylic and methacrylic ester, and then spray drying the coated granules to produce the polymer coated drug resin preparation. Cationic Drugs : 25 Cationic Drugs A cationic drug forms a complex with an anionic ion-exchange resin e.g. a resin with a SO3- group . In the G.I tract Hydronium ion (H+) in the gastrointestinal fluid penetrates the system and activity the release of cationic drug from the drug resin complex. H+ + Resin – SO3- Drug+ Resin – SO3- H+ +drug+. Anionic Drugs : 26 Anionic Drugs An anionic drug forms a complex with a cationic ion exchange resin, e.g. a resin with a [N (CH3)3+] group. In the GI tract , the Chloride ion (Cl-) in the gastrointestinal fluid penetrates the system and activates the release of anionic drug from the drug resin complex. Cl- + Resin –[N (CH3)3+] Drug- Resin –[NCH3)3+]Cl- + Drug- RELEASE KINETICS : 27 RELEASE KINETICS The mathematical models are used to evaluate the kinetics and mechanism of drug release from the tablets. The model that best fits the release data is selected based on the correlation coefficient (r) value in various models. The model that gives high ‘r’ value is considered as the best fit of the release data. Slide 28: 28 Mathematical models are 1)Zero order release model 2)First order release model 3)Hixson-crowell release model 4)Higuchi release model 5)Korsmeyer – peppas release model ZERO ORDER RELEASE EQUATION : 29 ZERO ORDER RELEASE EQUATION The equation for zero order release is Qt = Q0 + K0 t where Q0 = initial amount of drug Qt = cumulative amount of drug release at time “t” K0 = zero order release constant t = time in hours It describes the systems where the drug release rate is independent of its concentration of the dissolved substance. Slide 30: 30 A graph is plotted between the time taken on x-axis and the cumulative percentage of drug release on y-axis and it gives a straight line. FIRST ORDER RELEASE EQUATION : 31 FIRST ORDER RELEASE EQUATION The first order release equation is Log Qt = Log Q0+ Kt /2.303 where Q0 = initial amount of drug Qt = cumulative amount of drug release at time “t” K = first order release constant t = time in hours Here, the drug release rate depends on its concentration Slide 32: 32 A graph is plotted between the time taken on x-axis and the log cumulative percentage of drug remaining to be released on y-axis and it gives a straight line. HIXSON - CROWELL RELEASE EQUATION : 33 HIXSON - CROWELL RELEASE EQUATION The Hixson - Crowell release equation is Where Q0 = Initial amount of drug Qt = Cumulative amount of drug release at time “t” KHC = Hixson crowell release constant t = Time in hours. It describes the drug releases by dissolution and with the changes in surface area and diameter of the particles or tablets Slide 34: 34 A linear plot of the cube root of the initial concentration minus the cube root of percent remaining versus time in hours for the dissolution data in accordance with the Hixson-crowell equation. HIGUCHI RELEASE EQUATION : 35 HIGUCHI RELEASE EQUATION The Higuchi release equation is Q=KHt1/2 where Q = cumulative amount of drug release at time “t” KH = Higuchi constant t = time in hours The Higuchi equation suggests that the drug release by diffusion. A graph is plotted between the square root of time taken on x-axis and the cummulative percentage of drug release on y-axis and it gives a straight line. Slide 36: 36 KORSMEYER-PEPPAS EQUATION : 37 KORSMEYER-PEPPAS EQUATION Korsmeyer – peppas equation is F = (Mt /M ) = Kmtn Where F = Fraction of drug released at time ‘t’ Mt = Amount of drug released at time ‘t’ M = Total amount of drug in dosage form Km = Kinetic constant n = Diffusion or release exponent t = Time in hours Slide 38: 38 ‘n’ is estimated from linear regression of log ( Mt/M ) versus log t If n = 0.45 indicates fickian diffusion 0.45<n<0.89 indicates anomalous diffusion or non-fickian diffusion. If n = 0.89 and above indicates case-2 relaxation or super case transport-2. Anomalous diffusion or non-fickian diffusion refers to combination of both diffusion and erosion controlled rate release. Case-2 relaxation or super case transport-2 refers to the erosion of the polymeric chain. Slide 39: 39 A graph is plotted between the log time taken on x-axis and the log cummulative percentage of drug release on y-axis and it gives a straight line. ARTICLE REVIEW : 40 ARTICLE REVIEW Formulation, and Evaluation of Pentoxifylline-Loaded Poly(ἑ-caprolactone) Microspheres :- Slide 41: 41 ZERO ORDER RELEASE : 42 ZERO ORDER RELEASE FIRST ORDER RELEASE : 43 FIRST ORDER RELEASE HIGUCHI MODEL : 44 HIGUCHI MODEL Slide 45: 45 The in vitro release data were applied to various kinetics models to predict the drug release mechanism and kinetics. The drug release mechanism from the microspheres was diffusion controlled as plots of the amount released versus square root of time was found to be linear. The correlation coefficient(r2)was in the range of 0.978 0.987 for various formulations. When log percentage of drug remaining to be released vs. time was plotted in accordance with first order equation, straight lines were obtained (r2>0.95) indicated that drug release followed first order kinetics. REFERENCES : 46 REFERENCES Chein YW. Novel drug delivery systems. 2nded,pg:139-30 Brahmankar. Biopharmaceutics and pharmacokinetics . 5thed, pg: 350-25 Edith Mathiowitz. Encyclopedia of controlled drug delivery. 1sted, Vol.II, pg: 698-29. Wise DL. Hand book of pharmaceutical controlled release technology. 1sted, pg: 183-24. Tamizharasi S, Rathi JC, Rathi V. Formulation and evaluation of Pentoxifylline-loaded Poly(ἑ-caprolactone) microspheres . Ind J of Pharm Sci, 2008may; 70(3):333-5. Slide 47: 47 THANK YOU You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
Drug release mechanisms and kinetics vamsikrishnareddy 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: 8021 Category: Science & Tech.. License: All Rights Reserved Like it (19) Dislike it (0) Added: October 15, 2009 This Presentation is Public Favorites: 15 Presentation Description it describes the release mechanism of drugslike diffusion,dissolution Comments Posting comment... By: savitashetty (3 week(s) ago) Kindly send this presentation to savitashetty1@rediffmail.com. Thanks a million Saving..... Post Reply Close Saving..... Edit Comment Close By: alizarrabi (7 month(s) ago) Dear Sir, Thank you very much for the presentation. It was very useful for me. If possible, please let me have the ppt file of your presentation. Of course, if you let me use it. Thank you in advance. Email: zarrabi_a@yahoo.com Sincerely yours, Ali Saving..... Post Reply Close By: 03830 (7 month(s) ago) By: Dear Sir, Thank you very much for the presentation. It was very useful for me. If possible, please let me have the ppt file of your presentation. Of course, if you let me use it. Thank you in advance. Email: lyla81@yahoo.com Saving..... Edit Comment Close By: qqqqqqqqqqqqqqqqq (7 month(s) ago) dear sir , please send me this ppt at sandygalipelly@gmail.com, thankyou Saving..... Post Reply Close Saving..... Edit Comment Close By: rishi0043 (10 month(s) ago) hello sir plz post this ppt to my mail (rishi0043@gmail.com) i want todo project on this so send what ever u have plz sir i am nt getting much more information on this topic on internet plz sir dont forgot. thank you sir Saving..... Post Reply Close Saving..... Edit Comment Close By: suneethasusan (10 month(s) ago) Hello sir, please mail this ppt to ssc.31.7@gmail.com. thank you in advance Saving..... Post Reply Close Saving..... Edit Comment Close loading.... See all Premium member Presentation Transcript DRUG RELEASE MECHANISM AND KINETICS : 1 DRUG RELEASE MECHANISM AND KINETICS Submitted by B.VamsikrishnaReddy M.Pharm first year, Pharmaceutics, MCOPS, Manipal. Phone:+91-9008418512 vamsikrishnareddy57@gmail.com Slide 2: 2 DRUG DELIVERY SYSTEM :- Drug delivery System will deliver the drug at a rate determined by the needs of the body over a specified period of time. CONTROLLED RELEASE SYSTEM :- Control release is helpful for maintaining constant drug levels in the target tissues or cells. Slide 3: 3 TYPES OF CONTROLLED drug release SYSTEMS:- 1) Dissolution controlled systems a) Encapsulation dissolution controlled system. b) Matrix dissolution controlled systems. 2)Diffusion controlled systems a) Reservoir controlled systems. b) Matrix controlled systems. 3)Dissolution and diffusion controlled release systems Slide 4: 4 4)Water penetration controlled systems a) Swelling controlled systems b) Osmotically controlled systems. 5) Chemically controlled release systems a) erodible systems b) drug covalently linked with polymer 6) Hydro gels 7) Ion - exchange resin controlled release systems DISSOLUTION CONTROLLED SYSTEMS : 5 DISSOLUTION CONTROLLED SYSTEMS In dissolution controlled systems, the rate controlling step is dissolution. the drug is embedment in slowly dissolving or erodible matrix or by coating with slowly dissolving substances. It is of two types and they are Encapsulation dissolution controlled system Matrix dissolution controlled system ENCAPSULATION DISSOLUTION CONTROLLED SYSTEMS :- : 6 ENCAPSULATION DISSOLUTION CONTROLLED SYSTEMS :- The drug particles are coated or encapsulated by microencapsulation techniques with slowly dissolving materials like cellulose, poly ethylene glycols, polymethacrylates, waxes etc. the dissolution rate of coat depends upon the solubility and thickness of the coating. MATRIX DISSOLUTION CONTROLLED SYSTEMS :- : 7 MATRIX DISSOLUTION CONTROLLED SYSTEMS :- Matrix systems are also called as monoliths since the drug is homogeneously dispersed throughout a rate controlling medium. They employ waxes such as beeswax, carnauba wax, hydrogenated castor oil etc which control drug dissolution by controlling the rate of dissolution fluid penetration into the matrix by altering the porosity of rate. The wax embedded drug is generally prepared by dispersing the drug in molten wax and congealing and granulating the same. Slide 8: 8 DIFFUSION CONTROLLED RELEASE SYSTEMS:- : 9 DIFFUSION CONTROLLED RELEASE SYSTEMS:- Diffusion systems are characterized by release rate of drug is dependant on its diffusion through inert water insoluble membrane barrier. There are basically two types of diffusion devices. a) Reservoir diffusion system b) Matrix diffusion system Reservoir diffusion system : 10 Reservoir diffusion system MATRIX DIFFUSION SYSTEMS : 11 MATRIX DIFFUSION SYSTEMS DISSOLUTION AND DIFFUSION CONTROLLED RELEASE SYSTEMS : 12 DISSOLUTION AND DIFFUSION CONTROLLED RELEASE SYSTEMS The drug core is encased in a partially soluble membrane. Pores are thus created due to dissolution of parts of the membrane which Permit entry of aqueous medium into the core and hence drug dissolution occurs Allow diffusion of dissolved drug out of the system. An example of obtaining such a coating is using a mixture of ethyl cellulose with poly vinyl pyrrolidiene or methyl cellulose. Water Penetration Controlled Systems : 13 Water Penetration Controlled Systems In water penetration controlled delivery systems, rate control is obtained by the penetration of water into the system. They are Swelling Controlled Systems:- Swelling controlled release systems are initially dry and when placed in the body absorb water or other body fluids and swell. Swelling increases the aqueous solvent content within the formulation as well as the polymer mesh size, enabling the drug to diffuse through the swollen network into the external environment Slide 14: 14 “a” indicates reservoir diffusion swelling. “b” indicates matrix diffusion swelling. OSMOTICALLY CONTROLLED RELEASE SYSTEMS : 15 OSMOTICALLY CONTROLLED RELEASE SYSTEMS These systems are fabricated by encapsulating an osmotic drug core containing an osmotically active drug (or a combination of an osmotically inactive drug with an osmotically active salt eg NaCl) within a semi permeable membrane made from biocompatible polymer, e.g. cellulose acetate. A gradient of osmotic pressure is they created, under which the drug solutes are continuously pumped out over a prolonged period of time through the delivery orifice. Slide 16: 16 This type of drug system dispenses drug solutes continuously at a zero order rate. CHEMICALLY CONTROLLED RELEASE SYSTEMS : 17 CHEMICALLY CONTROLLED RELEASE SYSTEMS Chemically controlled release systems are the systems that change their chemical structure, when exposed to biological fluid. Mostly, biodegradable polymers are designed to degrade as a result of hydrolysis of the polymer chains into biologically safe and progressively smaller moieties. It is of two types and they are Erodible systems Pendent chain system Erodible systems : 18 Erodible systems In erodible systems, the mechanism of drug release occurs by erosion. Erosion may be two types and they are a) Bulk erosion process b) Surface erosion process Bulk erosion:- polymer degradation may occur through bulk hydrolysis. Surface erosion:- Polymers like polyorthoesters and polyanhydrides etc occurs degradation only at the surface of the polymer, resulting in a release rate that is proportional to the surface area of the delivery system. Slide 19: 19 “a” indicates bulk erosion “b” indicates surface erosion PENDENT CHAIN SYSTEM : 20 PENDENT CHAIN SYSTEM Pendent chain systems consists of linear homo or copolymers with the drug attached to the backbone chains. The drug is released from the polymer by hydrolysis or enzymatic degradation of the linkages. Zero order can be obtained and the cleavage of the drug is the rate controlling mechanism. Example for polymers used in pendent chain systems like n-(2-hydroxy propyl)methacrylamide etc. Hydrogels : 21 Hydrogels Hydrogels are water swollen three dimensional structures composed of primarily hydrophilic polymers. They are rendered insoluble because of chemical or physical cross-links. the physical cross-links include crystallites, entanglements or weak associations like hydrogen bonds or vander waals forces. these cross-links provide the physical integrity and network structure. Hydrogels provide desirable protection of labile drugs, peptides and proteins. Slide 22: 22 Because of their nature , hydrogels can be used in many different types of controlled release systems. These systems are classified according to the mechanism controlling the release of the drug from the device. They are classified as follows a) Diffusion controlled systems b) Swelling-controlled systems c) Chemically controlled systems d) Environmentally responsive systems Example for environmentally responsive systems : 23 Example for environmentally responsive systems . Ion-Exchange resins Controlled RELEASE SYSTEMS : 24 . Ion-Exchange resins Controlled RELEASE SYSTEMS This systems are designed to provide the controlled release of an ionic (or ionizable) drug . It is prepared by first absorbing an ionized drug onto the ion-exchange resin granules such as codeine base with Amberlite , and then after filtration from the alcoholic medium, coating the drug resin complex granules with a water permeable polymer, e.g. a modified copolymer of polyacrylic and methacrylic ester, and then spray drying the coated granules to produce the polymer coated drug resin preparation. Cationic Drugs : 25 Cationic Drugs A cationic drug forms a complex with an anionic ion-exchange resin e.g. a resin with a SO3- group . In the G.I tract Hydronium ion (H+) in the gastrointestinal fluid penetrates the system and activity the release of cationic drug from the drug resin complex. H+ + Resin – SO3- Drug+ Resin – SO3- H+ +drug+. Anionic Drugs : 26 Anionic Drugs An anionic drug forms a complex with a cationic ion exchange resin, e.g. a resin with a [N (CH3)3+] group. In the GI tract , the Chloride ion (Cl-) in the gastrointestinal fluid penetrates the system and activates the release of anionic drug from the drug resin complex. Cl- + Resin –[N (CH3)3+] Drug- Resin –[NCH3)3+]Cl- + Drug- RELEASE KINETICS : 27 RELEASE KINETICS The mathematical models are used to evaluate the kinetics and mechanism of drug release from the tablets. The model that best fits the release data is selected based on the correlation coefficient (r) value in various models. The model that gives high ‘r’ value is considered as the best fit of the release data. Slide 28: 28 Mathematical models are 1)Zero order release model 2)First order release model 3)Hixson-crowell release model 4)Higuchi release model 5)Korsmeyer – peppas release model ZERO ORDER RELEASE EQUATION : 29 ZERO ORDER RELEASE EQUATION The equation for zero order release is Qt = Q0 + K0 t where Q0 = initial amount of drug Qt = cumulative amount of drug release at time “t” K0 = zero order release constant t = time in hours It describes the systems where the drug release rate is independent of its concentration of the dissolved substance. Slide 30: 30 A graph is plotted between the time taken on x-axis and the cumulative percentage of drug release on y-axis and it gives a straight line. FIRST ORDER RELEASE EQUATION : 31 FIRST ORDER RELEASE EQUATION The first order release equation is Log Qt = Log Q0+ Kt /2.303 where Q0 = initial amount of drug Qt = cumulative amount of drug release at time “t” K = first order release constant t = time in hours Here, the drug release rate depends on its concentration Slide 32: 32 A graph is plotted between the time taken on x-axis and the log cumulative percentage of drug remaining to be released on y-axis and it gives a straight line. HIXSON - CROWELL RELEASE EQUATION : 33 HIXSON - CROWELL RELEASE EQUATION The Hixson - Crowell release equation is Where Q0 = Initial amount of drug Qt = Cumulative amount of drug release at time “t” KHC = Hixson crowell release constant t = Time in hours. It describes the drug releases by dissolution and with the changes in surface area and diameter of the particles or tablets Slide 34: 34 A linear plot of the cube root of the initial concentration minus the cube root of percent remaining versus time in hours for the dissolution data in accordance with the Hixson-crowell equation. HIGUCHI RELEASE EQUATION : 35 HIGUCHI RELEASE EQUATION The Higuchi release equation is Q=KHt1/2 where Q = cumulative amount of drug release at time “t” KH = Higuchi constant t = time in hours The Higuchi equation suggests that the drug release by diffusion. A graph is plotted between the square root of time taken on x-axis and the cummulative percentage of drug release on y-axis and it gives a straight line. Slide 36: 36 KORSMEYER-PEPPAS EQUATION : 37 KORSMEYER-PEPPAS EQUATION Korsmeyer – peppas equation is F = (Mt /M ) = Kmtn Where F = Fraction of drug released at time ‘t’ Mt = Amount of drug released at time ‘t’ M = Total amount of drug in dosage form Km = Kinetic constant n = Diffusion or release exponent t = Time in hours Slide 38: 38 ‘n’ is estimated from linear regression of log ( Mt/M ) versus log t If n = 0.45 indicates fickian diffusion 0.45<n<0.89 indicates anomalous diffusion or non-fickian diffusion. If n = 0.89 and above indicates case-2 relaxation or super case transport-2. Anomalous diffusion or non-fickian diffusion refers to combination of both diffusion and erosion controlled rate release. Case-2 relaxation or super case transport-2 refers to the erosion of the polymeric chain. Slide 39: 39 A graph is plotted between the log time taken on x-axis and the log cummulative percentage of drug release on y-axis and it gives a straight line. ARTICLE REVIEW : 40 ARTICLE REVIEW Formulation, and Evaluation of Pentoxifylline-Loaded Poly(ἑ-caprolactone) Microspheres :- Slide 41: 41 ZERO ORDER RELEASE : 42 ZERO ORDER RELEASE FIRST ORDER RELEASE : 43 FIRST ORDER RELEASE HIGUCHI MODEL : 44 HIGUCHI MODEL Slide 45: 45 The in vitro release data were applied to various kinetics models to predict the drug release mechanism and kinetics. The drug release mechanism from the microspheres was diffusion controlled as plots of the amount released versus square root of time was found to be linear. The correlation coefficient(r2)was in the range of 0.978 0.987 for various formulations. When log percentage of drug remaining to be released vs. time was plotted in accordance with first order equation, straight lines were obtained (r2>0.95) indicated that drug release followed first order kinetics. REFERENCES : 46 REFERENCES Chein YW. Novel drug delivery systems. 2nded,pg:139-30 Brahmankar. Biopharmaceutics and pharmacokinetics . 5thed, pg: 350-25 Edith Mathiowitz. Encyclopedia of controlled drug delivery. 1sted, Vol.II, pg: 698-29. Wise DL. Hand book of pharmaceutical controlled release technology. 1sted, pg: 183-24. Tamizharasi S, Rathi JC, Rathi V. Formulation and evaluation of Pentoxifylline-loaded Poly(ἑ-caprolactone) microspheres . Ind J of Pharm Sci, 2008may; 70(3):333-5. Slide 47: 47 THANK YOU