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Submitted by  B.VamsikrishnaReddy M.Pharm first year,  Pharmaceutics, MCOPS, Manipal. Phone:+91-9008418512 [email_address]  
<ul><li>DRUG DELIVERY SYSTEM   :-  </li></ul><ul><li>Drug delivery System  will  deliver  the drug  at a  rate determined ...
<ul><li>TYPES OF CONTROLLED DRUG RELEASE SYSTEMS:- </li></ul><ul><ul><li>1) Dissolution controlled systems </li></ul></ul>...
<ul><li>4)Water penetration controlled systems </li></ul><ul><li>a) Swelling controlled systems </li></ul><ul><li>b) Osmot...
DISSOLUTION CONTROLLED SYSTEMS  <ul><li>In dissolution controlled systems, the rate controlling step is dissolution. the d...
ENCAPSULATION DISSOLUTION CONTROLLED SYSTEMS :- <ul><li>The drug particles are coated or encapsulated by microencapsulatio...
MATRIX DISSOLUTION CONTROLLED SYSTEMS :- <ul><li>Matrix systems are also called as monoliths since the drug is homogeneous...
DIFFUSION CONTROLLED RELEASE SYSTEMS :-  <ul><li>Diffusion systems are characterized by release rate of drug is dependant ...
R eservoir  diffusion system
MATRIX  DIFFUSION SYSTEMS
DISSOLUTION AND DIFFUSION CONTROLLED RELEASE SYSTEMS <ul><li>The drug core is encased in a partially  soluble membrane. Po...
Water Penetration Controlled Systems <ul><li>In water penetration controlled delivery systems, rate control is obtained by...
“ a” indicates reservoir diffusion swelling. “ b” indicates matrix diffusion swelling.
OSMOTICALLY CONTROLLED  RELEASE  SYSTEMS <ul><li>These systems are fabricated by encapsulating an osmotic drug core contai...
This type of drug system dispenses drug solutes continuously at a zero order rate.
CHEMICALLY CONTROLLED RELEASE SYSTEMS <ul><li>Chemically controlled release systems are the systems that change their chem...
ERODIBLE SYSTEMS <ul><li>In erodible systems, the mechanism of  drug release occurs by erosion.  </li></ul><ul><li>Erosion...
“ a” indicates bulk erosion “ b” indicates surface erosion
PENDENT CHAIN SYSTEM <ul><li>Pendent chain systems consists of linear homo or copolymers with the drug attached to the bac...
HYDROGELS <ul><li>Hydrogels are water swollen three dimensional structures composed of primarily hydrophilic polymers. </l...
<ul><li>Because of their nature , hydrogels can be used in many different types of controlled release systems. These syste...
Example for environmentally responsive  systems
.  ION-EXCHANGE  RESINS CONTROLLED  RELEASE SYSTEMS <ul><li>  This systems are  designed to provide the controlled release...
CATIONIC DRUGS <ul><li>A cationic drug forms a complex with an anionic ion-exchange resin e.g. a resin with a  SO 3 - grou...
ANIONIC DRUGS <ul><li>An anionic drug forms a complex with a cationic ion exchange resin, e.g. a resin with a [N (CH 3 ) 3...
RELEASE KINETICS <ul><li>The mathematical models are used to evaluate the kinetics and mechanism of drug release from the ...
<ul><li>  Mathematical models are </li></ul><ul><li>1)Zero order release model </li></ul><ul><li>2)First order release mod...
ZERO ORDER  RELEASE EQUATION <ul><li>The equation for  zero order  release is </li></ul><ul><li>Q t  =  Q 0  +  K 0  t  </...
<ul><li>A graph is plotted between the time taken on x-axis and the cumulative percentage of drug release on y-axis and it...
FIRST ORDER RELEASE EQUATION <ul><li>The first order release equation is </li></ul><ul><li>Log Q t  =  Log Q 0 + Kt /2.303...
<ul><li>A graph is plotted between the time taken on x-axis and the log cumulative percentage of drug remaining to be rele...
HIXSON - CROWELL RELEASE  EQUATION  <ul><li>The Hixson - Crowell release equation is </li></ul><ul><li>Where </li></ul><ul...
<ul><li>A  linear plot of  the cube root of  the initial concentration minus  the cube root of percent remaining versus  t...
HIGUCHI RELEASE EQUATION <ul><li>The Higuchi  release  equation  is </li></ul><ul><li>Q=K H t 1/2 </li></ul><ul><li>where ...
KORSMEYER-PEPPAS EQUATION <ul><li>Korsmeyer – peppas equation is </li></ul><ul><li>F = (M t  /M ) = K m t n </li></ul><ul>...
<ul><li>‘ n’ is estimated from linear regression of  log ( M t /M ) versus log t </li></ul><ul><li>If  n = 0.45 indicates ...
<ul><li>A graph is plotted between the log time taken on x-axis and the log cummulative percentage of drug release on y-ax...
ARTICLE REVIEW <ul><li>Formulation, and Evaluation of Pentoxifylline-Loaded Poly(ἑ-caprolactone) Microspheres :- </li></ul...
ZERO ORDER RELEASE
FIRST ORDER RELEASE
HIGUCHI MODEL
<ul><li>The  in vitro  release data were applied to various kinetics models to predict the drug release mechanism and kine...
REFERENCES <ul><li>Chein YW. Novel drug delivery systems .  2 nd ed,pg:139-30 </li></ul><ul><li>Brahmankar. Biopharmaceuti...
<ul><li>THANK  YOU </li></ul>
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Drug Release Mechanism And Kinetics

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it describes the controlled drug release by diffusion or dissolution or both or swelling or erosion and which kinetics it follows either zero,first , higuchi or peppas

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Drug Release Mechanism And Kinetics

  1. 1. Submitted by B.VamsikrishnaReddy M.Pharm first year, Pharmaceutics, MCOPS, Manipal. Phone:+91-9008418512 [email_address]  
  2. 2. <ul><li>DRUG DELIVERY SYSTEM :- </li></ul><ul><li>Drug delivery System will deliver the drug at a rate determined by the needs of the body over a specified period of time. </li></ul><ul><li>CONTROLLED RELEASE SYSTEM :- </li></ul><ul><li> Control release is helpful for maintaining constant drug levels in the target tissues or cells. </li></ul>
  3. 3. <ul><li>TYPES OF CONTROLLED DRUG RELEASE SYSTEMS:- </li></ul><ul><ul><li>1) Dissolution controlled systems </li></ul></ul><ul><li>a) Encapsulation dissolution controlled system. </li></ul><ul><li>b) Matrix dissolution controlled systems. </li></ul><ul><li> 2)Diffusion controlled systems </li></ul><ul><li>a) Reservoir controlled systems. </li></ul><ul><li>b) Matrix controlled systems. </li></ul><ul><li> 3)Dissolution and diffusion controlled release </li></ul><ul><li>systems </li></ul>
  4. 4. <ul><li>4)Water penetration controlled systems </li></ul><ul><li>a) Swelling controlled systems </li></ul><ul><li>b) Osmotically controlled systems. </li></ul><ul><li>5) Chemically controlled release systems </li></ul><ul><li>a) erodible systems </li></ul><ul><li>b) drug covalently linked with polymer </li></ul><ul><li>6) Hydro gels </li></ul><ul><li>7) Ion - exchange resin controlled release systems </li></ul>
  5. 5. DISSOLUTION CONTROLLED SYSTEMS <ul><li>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. </li></ul><ul><li> </li></ul><ul><li>It is of two types and they are </li></ul><ul><ul><ul><li>Encapsulation dissolution controlled system </li></ul></ul></ul><ul><ul><ul><li>Matrix dissolution controlled system </li></ul></ul></ul>
  6. 6. ENCAPSULATION DISSOLUTION CONTROLLED SYSTEMS :- <ul><li>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. </li></ul>
  7. 7. MATRIX DISSOLUTION CONTROLLED SYSTEMS :- <ul><li>Matrix systems are also called as monoliths since the drug is homogeneously dispersed throughout a rate controlling medium. </li></ul><ul><li>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. </li></ul><ul><li>The wax embedded drug is generally prepared by dispersing the drug in molten wax and congealing and granulating the same. </li></ul>
  8. 8.
  9. 9. DIFFUSION CONTROLLED RELEASE SYSTEMS :- <ul><li>Diffusion systems are characterized by release rate of drug is dependant on its diffusion through inert water insoluble membrane barrier. </li></ul><ul><li> There are basically two types of diffusion devices. </li></ul><ul><li>a) R eservoir diffusion system </li></ul><ul><li>b) Matrix diffusion system </li></ul>
  10. 10. R eservoir diffusion system
  11. 11. MATRIX DIFFUSION SYSTEMS
  12. 12. DISSOLUTION AND DIFFUSION CONTROLLED RELEASE SYSTEMS <ul><li>The drug core is encased in a partially soluble membrane. Pores are thus created due to dissolution of parts of the membrane which </li></ul><ul><ul><li>Permit entry of aqueous medium into the core and hence drug dissolution occurs </li></ul></ul><ul><ul><li>Allow diffusion of dissolved drug out of the system. </li></ul></ul><ul><li> An example of obtaining such a coating is using a mixture of ethyl cellulose with poly vinyl pyrrolidiene or methyl cellulose. </li></ul>
  13. 13. Water Penetration Controlled Systems <ul><li>In water penetration controlled delivery systems, rate control is obtained by the penetration of water into the system. They are </li></ul><ul><li>Swelling Controlled Systems:- </li></ul><ul><li>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 environme nt </li></ul>
  14. 14. “ a” indicates reservoir diffusion swelling. “ b” indicates matrix diffusion swelling.
  15. 15. OSMOTICALLY CONTROLLED RELEASE SYSTEMS <ul><li>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. </li></ul><ul><li>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. </li></ul>
  16. 16. This type of drug system dispenses drug solutes continuously at a zero order rate.
  17. 17. CHEMICALLY CONTROLLED RELEASE SYSTEMS <ul><li>Chemically controlled release systems are the systems that change their chemical structure, when exposed to biological fluid. </li></ul><ul><li>Mostly, biodegradable polymers are designed to degrade as a result of hydrolysis of the polymer chains into biologically safe and progressively smaller moieties. </li></ul><ul><li>It is of two types and they are </li></ul><ul><ul><ul><li>Erodible systems </li></ul></ul></ul><ul><ul><ul><li>Pendent chain system </li></ul></ul></ul>
  18. 18. ERODIBLE SYSTEMS <ul><li>In erodible systems, the mechanism of drug release occurs by erosion. </li></ul><ul><li>Erosion may be two types and they are </li></ul><ul><li>a) Bulk erosion process </li></ul><ul><li>b) Surface erosion process </li></ul><ul><li>Bulk erosion:- </li></ul><ul><li>polymer degradation may occur through bulk hydrolysis. </li></ul><ul><li>Surface erosion:- </li></ul><ul><li>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 . </li></ul>
  19. 19. “ a” indicates bulk erosion “ b” indicates surface erosion
  20. 20. PENDENT CHAIN SYSTEM <ul><li>Pendent chain systems consists of linear homo or copolymers with the drug attached to the backbone chains. </li></ul><ul><li>The drug is released from the polymer by hydrolysis or enzymatic degradation of the linkages. </li></ul><ul><li>Zero order can be obtained and the cleavage of the drug is the rate controlling mechanism. </li></ul><ul><li>Example for polymers used in pendent chain systems like n-(2-hydroxy propyl)methacrylamide etc. </li></ul>
  21. 21. HYDROGELS <ul><li>Hydrogels are water swollen three dimensional structures composed of primarily hydrophilic polymers. </li></ul><ul><li>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. </li></ul><ul><li>Hydrogels provide desirable protection of labile drugs, peptides and proteins. </li></ul>
  22. 22. <ul><li>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 </li></ul><ul><li>a) Diffusion controlled systems </li></ul><ul><li>b) Swelling-controlled systems </li></ul><ul><li>c) Chemically controlled systems </li></ul><ul><li>d) Environmentally responsive systems </li></ul>
  23. 23. Example for environmentally responsive systems
  24. 24. . ION-EXCHANGE RESINS CONTROLLED RELEASE SYSTEMS <ul><li>  This systems are designed to provide the controlled release of an ionic (or ionizable) drug . </li></ul><ul><li>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. </li></ul>
  25. 25. CATIONIC DRUGS <ul><li>A cationic drug forms a complex with an anionic ion-exchange resin e.g. a resin with a SO 3 - group . </li></ul><ul><li>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 . </li></ul><ul><li>H + + Resin – SO 3 - Drug + Resin – SO 3 - H + +Drug + . </li></ul>
  26. 26. ANIONIC DRUGS <ul><li>An anionic drug forms a complex with a cationic ion exchange resin, e.g. a resin with a [N (CH 3 ) 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. </li></ul><ul><li>Cl - + Resin –[N (CH 3 ) 3 + ] Drug- </li></ul><ul><li>Resin –[NCH 3 ) 3 + ]Cl - + Drug- </li></ul>
  27. 27. RELEASE KINETICS <ul><li>The mathematical models are used to evaluate the kinetics and mechanism of drug release from the tablets. </li></ul><ul><li>The model that best fits the release data is selected based on the correlation coefficient (r) value in various models. </li></ul><ul><li>The model that gives high ‘r’ value is considered as the best fit of the release data. </li></ul>
  28. 28. <ul><li> Mathematical models are </li></ul><ul><li>1)Zero order release model </li></ul><ul><li>2)First order release model </li></ul><ul><li>3)Hixson-crowell release model </li></ul><ul><li>4)Higuchi release model </li></ul><ul><li>5)Korsmeyer – peppas release model </li></ul>
  29. 29. ZERO ORDER RELEASE EQUATION <ul><li>The equation for zero order release is </li></ul><ul><li>Q t = Q 0 + K 0 t </li></ul><ul><li>where </li></ul><ul><li>Q 0 = initial amount of drug </li></ul><ul><li>Q t = cumulative amount of drug release at time “t” </li></ul><ul><li>K 0 = zero order release constant </li></ul><ul><li>t = time in hours </li></ul><ul><li>It describes the systems where the drug release rate is independent of its concentration of the dissolved substance. </li></ul>
  30. 30. <ul><li>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 . </li></ul>
  31. 31. FIRST ORDER RELEASE EQUATION <ul><li>The first order release equation is </li></ul><ul><li>Log Q t = Log Q 0 + Kt /2.303  </li></ul><ul><li>where </li></ul><ul><li>Q 0 = initial amount of drug </li></ul><ul><li>Q t = cumulative amount of drug release at time “t” </li></ul><ul><li>K = first order release constant </li></ul><ul><li>t = time in hours </li></ul><ul><li>Here, the drug release rate depends on its concentration </li></ul>
  32. 32. <ul><li>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. </li></ul>
  33. 33. HIXSON - CROWELL RELEASE EQUATION <ul><li>The Hixson - Crowell release equation is </li></ul><ul><li>Where </li></ul><ul><li>Q 0 = Initial amount of drug </li></ul><ul><li>Q t = Cumulative amount of drug release at time “t” </li></ul><ul><li>K HC = Hixson crowell release constant </li></ul><ul><li>t = Time in hours. </li></ul><ul><li>It describes the drug releases by dissolution and with the changes in surface area and diameter of the particles or tablets </li></ul>
  34. 34. <ul><li>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. </li></ul>
  35. 35. HIGUCHI RELEASE EQUATION <ul><li>The Higuchi release equation is </li></ul><ul><li>Q=K H t 1/2 </li></ul><ul><li>where </li></ul><ul><li>Q = cumulative amount of drug release at time “t” </li></ul><ul><li>K H = Higuchi constant </li></ul><ul><li>t = time in hours </li></ul><ul><li>The Higuchi equation suggests that the drug release by diffusion. </li></ul><ul><li>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. </li></ul>
  36. 36.
  37. 37. KORSMEYER-PEPPAS EQUATION <ul><li>Korsmeyer – peppas equation is </li></ul><ul><li>F = (M t /M ) = K m t n </li></ul><ul><li>Where </li></ul><ul><li>F = Fraction of drug released at time ‘t’ </li></ul><ul><li>M t = Amount of drug released at time ‘t’ </li></ul><ul><li>M = Total amount of drug in dosage form </li></ul><ul><li>K m = Kinetic constant </li></ul><ul><li> n = Diffusion or release exponent </li></ul><ul><li> t = Time in hours </li></ul>
  38. 38. <ul><li>‘ n’ is estimated from linear regression of log ( M t /M ) versus log t </li></ul><ul><li>If n = 0.45 indicates fickian diffusion </li></ul><ul><li>0.45<n<0.89 indicates anomalous diffusion or non-fickian diffusion. </li></ul><ul><li>If n = 0.89 and above indicates case-2 relaxation or super case transport-2 . </li></ul><ul><li>Anomalous diffusion or non-fickian diffusion refers to combination of both diffusion and erosion controlled rate release. </li></ul><ul><li>Case-2 relaxation or super case transport-2 refers to the erosion of the polymeric chain. </li></ul>
  39. 39. <ul><li>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. </li></ul>
  40. 40. ARTICLE REVIEW <ul><li>Formulation, and Evaluation of Pentoxifylline-Loaded Poly(ἑ-caprolactone) Microspheres :- </li></ul><ul><li>  </li></ul>
  41. 41.
  42. 42. ZERO ORDER RELEASE
  43. 43. FIRST ORDER RELEASE
  44. 44. HIGUCHI MODEL
  45. 45. <ul><li>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. </li></ul><ul><li>The correlation coefficient(r 2 )was in the range of 0.978 0.987 for various formulations. </li></ul><ul><li>When log percentage of drug remaining to be released vs. time was plotted in accordance with  first order equation, straight lines were obtained (r 2 >0.95) indicated that drug release followed   first order kinetics. </li></ul>
  46. 46. REFERENCES <ul><li>Chein YW. Novel drug delivery systems . 2 nd ed,pg:139-30 </li></ul><ul><li>Brahmankar. Biopharmaceutics and pharmacokinetics . 5 th ed, pg: 350-25 </li></ul><ul><li>Edith Mathiowitz. Encyclopedia of controlled drug delivery. 1 st ed, Vol.II, pg: 698-29. </li></ul><ul><li>Wise DL. Hand book of pharmaceutical controlled release technology. 1 st ed, pg: 183-24. </li></ul><ul><li>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. </li></ul><ul><li>  </li></ul>
  47. 47. <ul><li>THANK YOU </li></ul>

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