Controlled drugdeliverysystem
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  • 1. Osmotically Controlled Systems • osmotic pressure provides the driving force to generate controlled release of drug. • Consider a semipermeable membrane that is permeable to water, but not to drug. When this device is exposed to water or any body fluid, water will flow into the tablet owing to the osmotic pressure difference. dV/dt= Ak/h(∆Π−∆P) k=membrane permeability, A=area of the membrane, h=membrane thickness ∆Π = osmotic pressure difference, ∆P =hydrostatic pressure difference 1
  • 2. 2 Type A contains a osmotic core with drug Type B contains the drug solution in a flexible bag, with the osmotic core surrounding
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  • 4. Characteristics of Osmotically Controlled Devices Advantages Zero-order release is obtainable Peformulation is not required for different drugs release of drug is independent of environment of the system Disadvantages systems can be very expensive quality control is more extensive 4
  • 5. Hydrodynamic Pressure Controlled Systems • Hydrodynamic pressure generated by swelling of a hydrophilic gum • The device comprises of a rigid, shape retaining housing enclosing a collapsible, impermeable containing liquid drug • The gun imbibes water in GIT through an opening at the lower side of external housing and swells creating an hydrodynamic pressure • The pressure thus created squeeze the collapsible drug reservoir to release the medicament through the delivery orifice 5
  • 6. Principle:- In this system a semipermeable membrane around a core of an osmotically active drug or a core of an osmotically inactive drug in combination with an osmotically active salt. The drug either in the from of solid or as solution. Semipermiable housing having controlled water permeability,the drug is activated to release in solution form at a constant rate through a special delivery orifice. If the drug is solution so the intrinsic rate of drug release Q/t is given by: Q/t = Pw Am /hm (πs-πe ) If the drug is solid so the intrinsic rate of drug release Q/t is given by: Q/t = Pw Am /hm (πs-πe)Sd where, Pw = water permeability, Am = effective surface area, hm = thickness of the semipermiable housing, (πs-πe)=deferential osmotic pressure b/w drug delivery system and external environment, Sd=aqueous solubility of the drug contained in solid formulation.
  • 7. Materials used Semipermiable membrane Hydrophilic and hydrophobic polymers Wicking agents Solubilizing agents Surfactants Coating solvents Plasticizers Flux regulators Pore forming agents Classification of osmotic pumps Oral osmotic pumps ,Elementary osmotic pump,Push-pull osmotic pump ,Controlled porosity osmotic pumps,Osmotic bursting osmotic pumps,Combination of effervescent agents with the drug Pump for insoluble drugs,Sandwiched Osmotic tablet systems Elementary osmotic pump It consists of an osmotic core containing drug which is coated with semi permeable membrane usually cellulose acetate with delivery orifice. The core may or may not contain an osmotic agent depending upon the osmotic activity of the drug.
  • 8. Mechanism :-The water penetrates inside the dosage form at the rate determined by the fluid permeability of the membrane and osmotic pressure of core formulation. This will result in formation of saturated solution of drug within the core, which is dispensed at a controlled rate from the delivery orifice in the membrane. Push-pull osmotic pump:-It is a modified elementary osmotic pump through which it is possible to deliver both poorly water soluble and highly water soluble drugs at a constant rate. After coming in contact with the aqueous environment, polymeric osmotic layer swells and pushes the drug layer, and thus releasing drug in the form of fine dispersion via the orifice. Controlled porosity osmotic pumps:-This type of osmotic pump consists of 2 layers of membrane.The inner is microporous membrane, which is made up of cellulosic material containing some pore forming agents, covered by a semipermeable membrane.When the system is placed in an aqueous environment the soluble components of first layer of coating dissolve, resulting in a microporous membrane, which provides greater flux of water into the system
  • 9. MICROPOROUS MEMBRANE:- Osmotic bursting pumps:- When it is placed in an aqueous environment, water is imbibed and hydraulic pressure is built up inside until the wall ruptures and the contents are released to the environment.Varying the thickness as well as the area the semipermeable membrane can control release of drug. This system is useful to provide pulsated drug release.1 Sandwiched osmotic tablets:- It is composed of polymeric push layer sandwiched between two drug layers with two delivery orifices. When placed in the aqueous environment the middle push layer containing the swelling agents swells and the drug is released from the two orifices situated on opposite sides of the tablet and thus SOTS can be suitable for drugs prone to cause local irritation of the gastric mucosa.
  • 10. SEMI PERMEABLE MEMBRANE WITH PLASTICIZER Advantages of osmotic drug delivery Delivers drug at zero order release kinetics. Delivery rate is independent of pH and outside agitation. Delivery of drug takes place in solution form which is ready for absorption. Due to its zero order release profile it is used in very early stages of drug research, such as drug screening, animal toxicology and pharmacology.19. Limitations Disadvantages of osmotic drug delivery Special equipment is required for making an orifice in the system. Residence time of the system in body varies with the gastric motility and food intake. It may cause irritation or ulcer due to release of saturated solution of drug. Costly process.
  • 11. HYDRODYNAMICALLY BALANCED DRUG DELIVERY SYSTEM. Hydrodynamically balanced system are also known as floating drug delivery system.In this system the reservoir is homogenously dispersed in a swellable polymer matrix fabricated from a hydrophilic polymer.. PRINCIPLE In GIT the laminate absorbs GI fluids & become increasingly swollen, which generate hydrodynamic pressure in the system,the hydrodynamic pressure thus created forces the drug reservior compartment to reduce in volume and causes the liquid drug formulation to release through the delivery orifice at a rate defined by :- Q / t=Pf Am/ hm( s - e) Pf = Fluid permeability,ɵ ɵ Am = Effective surface area , hm= Thickness of wall with annular openings, ( s - e )= Difference in the hydrodynamicɵ ɵ pressure between the drug delivery system( s) & theɵ environment ( e).ɵ
  • 12. HYDRODYNAMICALLY ACTIVATED DRUG DELIVERY SYSTEM Hydrodynamic pressure activated drug delivery system can be fabricated by enclosing a collapsible, impermeable container, which contains a liquid drug formulation to form a drug reservoir compartment.Inside a rigid shape retaining housing a composite laminate of an absorbent layer and a swellable hydrophilic polymer layer is sandwiched between the drug reservoir compartment and the rigid housing. Types of Hydro dynamically balanced system 1. Effervescent system 2. Non Effervescent system EFFERVESCENT SYSTEM These floating drug delivery system are prepared in such a manner that when they come in contact with stomach fluid , CO2 is generated, & remain entrapped in hydrocolloid gel. This leads to an upward flow of the dosage form and maintains it in a floating condition.
  • 13. 09/08/2010 KLE COP, NIpani 14 Multiple-unit oral floating drug delivery system . (A)Multiple-unit oral floating drug delivery system. (B)Working principle of effervescent floating drug delivery system. Multiple-unit oral floating drug delivery system 28Figure . (A) Multiple-unit oral floating drug delivery system. (B) Working principle of effervescent floating drug delivery system.
  • 14. 15 NON EFFERVESCENT SYSTEM: It consists of two major components: Gel forming or swellable cellulose type of hydrocolloids & polysaccharides. Matrix forming polymers (polycarbonate, polyacrylate, polymethacrylate & polystyrene). MECHANISM Gel forming hydrocolloids swells in contact with gastric fluid after oral administration and maintains a relative integrity of shape and a bulk density of less than unity within gastric environment. The air thus trapped by the swollen polymer imparts buoyancy to the dosage form.The gel barrier controls the rate of solvent penetration into the device & the rate of drug release from the device. It maintains a bulk density of <1 and thus remains buoyant in the gastric fluid inside the stomach for upto 6 hrs; conventional dosage forms disintegrate completely within 60 min and are emptied totally from the stomach shortly afterward. Advantages of HBS:-Delivery of drugs for local action in stomach. Minimizing the mucosal irritation due to drugs, by drug releasing slowly at controlled rate Site specific drug delivery.
  • 15. Treatment of gastro intestinal disorders such as gastro- esophageal reflux.Simple and conventional equipments required for manufacture.Ease of administration and better patient compliance. pH- Activated Drug Delivery :- This type of activation controlled drug delivery system permits targeting the delivery of drug only in the region with the selected pH range. Drugs administered orally would encounter a spectrum of pH ranging from 7 in the mouth, 1 - 4 in the stomach and 5 - 7 in the intestine. Prepared by first blending an acidic or basic drug with one or more buffering agents (Eg. primary, secondary, tertiary salt of citric acid) granulating with appropriate pharmaceutical excipients to form small granules and then coating the granules with a gastrointestinal fluid permeable film forming polymer (Cellulose derivatives).
  • 16. 17 The polymer coating controls the permeation of gastrointestinal fluid. The gastrointestinal fluid permeating into the device is adjusted by the buffering agents to an appropriate constant pH, at which the drug dissolves and is delivered through the membrane at a constant rate regardless of the location of the device in the alimentary canal. It is also fabricated by coating the drug containing core with a pH sensitive polymer combination For instance, a gastric fluid labile drug is protected by encapsulating it inside a polymer membrane that resists the degradative action of gastric pH, such as the combination of ethyl cellulose and hydroxyl methyl cellulose phthalate. In the stomach, coating membrane resists the action of gastric fluid (pH<3) & the drug molecule is thus protected from acid degradation. After gastric emptying the drug delivery system travels to the small intestine and the intestinal fluid solubulize the hydroxyl methyl cellulose phthalate component from the coating membrane. This leaves a microporous membrane of intestinal fluid insoluble polymer of Ethyl cellulose, which controls the release of drug from the core tablet.
  • 17. The drug solute is thus delivered at a controlled manner in the intestine by a combination of drug dissolution and pore channel diffusion Cellulose acetate tri-melliate. Cellulose acetate phthalate Poly vinyl acetate phthalate Hydroxy propyl methyl phthalate-50 Eudragt –D 30 Eudragt –L100 Eudragt –S100 18
  • 18. Ion-Exchange Systems • Ion-exchange systems generally use resins composed of water soluble cross-linked polymers • These polymers contain salt forming functional groups in repeating position on the polymer chain • The drug is bound to the resin and released by exchanging with appropriately charged ions in contact with the ion exchange groups Resin+ - drug- + X- resin+ - X- + drug- WhereX-areionsin theGItract 19
  • 19. ION EXCHANGE RESINATES AS CONTROL DRUG DELIVERY SYSTEM Principle A Cation exchange resin generally has Sulphonic and Carboxylic functional groups as an integral part of the resin and an equivalent amount of cationic drug molecules. An Anion exchange resin generally has quaternary ammonium groups and polyalkylamine functional groups as an integral part of the resin and an equivalent amount of anionic drug molecules. Types of ion-exchange resins Drugs Suitable for Resinate Preparation Drugs should have acidic and basic groups in their chemical structure. Biological half life should be between 2-6 hrs, drugs with t1/2 < 1 hr or > 8 hrs are difficult to formulate. The drug is to be absorbed from all regions of GI tract. Drugs should be stable sufficiently in the gastric juice09/08/2010 KLE COP, NIpani 20
  • 20. Some Important Properties of Ion-Exchange Resins Particle Size and form Porosity Swelling Ion exchange capacity General preparation of drug resinatesColumn process: A highly concentrated drug solution is eluted through a bed or column of the resin until equilibrium is established. Batch process: The resin particles are stirred with a large volume of concentrated drug solution. AdvantagesIon – exchange resonates of drug can help in reducing the dose.Reduced fluctuations in blood and tissue concentration level can be achieved.Protection of drug from gastric enzymes.Controlled release. LimitationsThe release rate is proportional to the concentration of the ions present in the area of administration.The release rate of drug can be affected by variability in diet, water intake and individual intestinal content. 21
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