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  • The EOP was developed by Alza undre the name OROS for controlled release oral drug delivery formulations

    1. 1. Presented by: RITEKSHA PATEL M.PHARMACY
    3. 3. 1. Introduction 1. Osmotic drug delivery uses the osmotic pressure for controlled delivery of drugs by using osmogens. 2. Osmosis : It refers to the process of movement of solvent from lower concentration of solute towards higher concentration of solute across the semipermeable membrane. 3. Osmotic pressure: The pressure exerted by the flow of water through a semipermeable membrane separating two solutions with different concentrations of solute. 4. These systems can be used for both route of administration i.e. oral and parenterals. 3
    4. 4. 2.Principle of osmosis Abbe Nollet first reported osmotic effect in 1748, but Pfeffer in 1877 had been the pioneer of quantitative measurement of osmotic effect. Van’t Hoff established the analogy between the Pfeffer results and the ideal gas laws by the expression π = n2RT Where n2 represents the molar concentration of sugar (or other solute) in the solution, R depicts the gas constant, and T the temperatue. 4
    5. 5. 3. Basic component of osmotic DDS 1. Drug : itself may act as osmogen otherwise osmogenic salt can be added in formulation 2. Semipermeable membrane: criteria: Sufficient wet strength and water permeability Should be biocompatible and rigid Should be sufficient thick to withstand the pressure within the device Any polymer that is permeable to water but impermeable to solute can be used as a coating material in osmotic devices Ex. Cellulose Acetate, Cellulose Triacetate and Ethyl Cellulose 5
    6. 6. 3. Hydrophilic and hydrophobic polymers :( CMC, HEC, HPMC ) 4. Wicking agent : ( SLS, PVP, bentonite ) 5. Solubilizing agent :(PVP, CD, PEG ) 6. Osmogens:( NACL, KCL) 7. Surfactants : (poly oxyethylenated caster oil) 8. Coating solvent : ( acetone and methanol 80:20,acetone and water 90:10 ) 9. Plasticizer : ( phthalates, benzoates, TEC ) 10. Flux regulator : ( poly propylene, poly butylene ) 11. Pore forming agent:( Calcium nitrate , potassium sulphate) 6
    7. 7. 4. Classification of osmotic DDS 1. Implantable Osmotic Drug Delivery System 2. Oral Osmotic Drug Delivery System 7
    8. 8. 1. IMPLANTABLE OSMOTIC DDS A. ROSE NELSON PUMP Drug Chamber Elastic Diaphragm Salt Chamber Rigid Semi permeable membrane Water Chamber Delivery orifice 8
    9. 9. B. HIGUCHI LEEPER OSMOTIC PUMP 1. It has no water chamber, and the activation of the device occurs after imbibitions of the water from surrounding environment. 2. Widely employed for veterinary use. It is either swallowed or implanted in body of an animal for delivery of antibiotics or growth hormones to animal. Porous Membrane Support MgSO4 Movable Separator Drug Chamber Rigid Housing Satd. Sol. Of MgSO4 contg. Solid MgSO4 Semi-permeable Membrane 9
    10. 10. PULSATILE RELEASE OSMOTIC PUMP 1. The system is in the form of a capsule from which the drug is delivered by the capsule’s osmotic infusion. 2. The delivery orifice opens intermittently to achieve a pulsatile delivery effect. 3. As the osmotic infusion progresses, pressure rises within the capsule, causing the wall to stretch. 4. Elastomers such as styrene-butadiene copolymer can be used. Osmogen Semi permeable Membrane Separating Barrier Elastic Cap Movable piston Drug Solution Tiny orifice opened upon stretches under the Osmotic pressure 10
    11. 11. C. HIGUCHI THEEUWES OSMOTIC PUMP 1. In this device, the rigid housing is consist of a semi permeable membrane. The drug is loaded in the device only prior to its application, which extends advantage for storage of the device for longer duration. 2. Diffusional loss of the drug from the device is minimized by making the delivery port in shape of a long thin tube. Wall of flexible collapsible material SPM Coating contg. Solid Osmotic compound Delivery port Osmotic Agent layer Rigid Semi permeable Membrane Fluid to be pumped Delivery port Swollen Osmogen layer Squeezed Drug Core 11
    12. 12. Principle of Operation ALZET pumps have 3 concentric layers: 1. Rate-controlling, semi-permeable membrane 2. Osmotic layer 3. Impermeable drug reservoir ALZET pumps work by osmotic displacement. Water enters the pump across the outer, semi-permeable membrane due to the presence of a high concentration of sodium chloride in the osmotic chamber. The entry of water causes the osmotic chamber to expand, thereby compressing the flexible reservoir and delivering the drug solution through the delivery portal. 12
    13. 13. 2. ORAL OSMOTIC DDS A. Elementary osmotic pump B. Modified osmotic pump C. Multichamber osmotic pump - expandable - non expandable D. Controlled porosity osmotic pump E. Multiparticulate delayed release system F. Monolithic osmtic system 13
    14. 14. A. Elementary osmotic pump Semi permeable membrane Core Delivery Orifice 1. Major method of achieving controlled drug release. 2. The EOP was developed by Alza undre the name OROS for controlled release oral drug delivery formulations. 14
    15. 15. B.MODIFICATIONS IN ELEMENTARY OSMOTIC PUMP 1. The first layer is made up of thick micro porous film that provides the strength required to withstand the internal pressure, while second layer is composed of thin semi permeable membrane that produces the osmotic flux. 2. The support layer is formed by: Cellulose acetate coating containing 40 to 60% of pore forming agent such as sorbitol. Delivery orifice Drug chamberInner microporous membrane Outer semi permeable membrane 15
    16. 16. DELIVERY OF INSOLUBLE DRUG 1. Coating osmotic agent with elastic semi permeable film 2. Mixing of above particles with the insoluble drug 3. Resultant mixture is coated with the rigid semi permeable membrane x x x x x x x x x x x x x x Elastic SPM Rigid SPM Insoluble Particles 16
    17. 17. C. Multichamber osmotic pump 1. Multiple chamber osmotic pumps can be divided into two major classes a) Tablets with a second expandable osmotic chamber b) Tablets with a non-expanding second chamber a) Tablets with a second expandable osmotic chamber Osmotic Drug Core SPM Delivery Orifice Delivery Orifice Polymer push compartment Expanded push compartment Before operation During operation 17
    18. 18. b) Tablet with non expanding second chamber Depending on function of second chamber non–expandable osmotic pump are divided into, Drug solution get diluted in second chamber before leaving device. Two separate EOP tablet formed in single tablet 18
    19. 19. OROS TRI-LAYER 19
    20. 20. DUROS 20
    21. 21. D.CONTROLLED PORSITY OSMOTIC PUMPS 1. They are not having any aperture for release of drugs. The drug release is achieved by the pores, which are formed in the semi permeable wall in situ during the operation. 2. The semi permeable coating membrane contains water- soluble pore forming agents. This membrane after formation of pores becomes permeable for both water and solutes. Coating Containing Pore Forming Agents Pore Formation and Subsequent Drug Release Aqueous Environment 21
    22. 22. E. Multiparticulate delayed release system 1. In the multiparticulate delayed-release system, pellets containing drug with or without osmotic agent are coated with an SPM-like cellulose acetate. 2. On contact with an aqueous environment, water penetrates into the core and forms a saturated solution of soluble components. 3. The osmotic pressure gradient induces a water influx, resulting in a rapid expansion of the membrane, leading to the formation of pores. 4. The osmotic ingredient and the drug are released through these pores according to zero order kinetics. 22
    23. 23. F. Monolithic osmtic system 1. Dispersion of water soluble drug is made in a polymeric matrix and compressed as tablet. 2. Tablet is then coated with semi permeable membrane. 3. When MOS comes in contact with aqueous environment, the water penetrates in the core and forms a saturated solution of component which will generate osmotic pressure which results in the rupturing of membrane of polymeric matrix surrounding the agent. Thus liberating drug to move outside the environment. 23
    24. 24. 5. Factors affecting release of medicament from Osmotic DDS A. Solubility B. Osmotic pressure C. Delivery orifice D. Membrane A. Solubility 1. Solubility of drug is one of the most important factors since kinetic of osmotic release is directly related to the drug solubility. 2. Both highly soluble and poorly soluble drugs are not good candidates for osmotic drug delivery. 24
    25. 25. B. Osmotic pressure 1. The next release-controlling factor that must be optimized is the osmotic pressure gradient between inside the compartment and the external environment. 2. The release rate of a drug from an osmotic system is directly proportional to the osmotic pressure of the core formulation C. Delivery orifice 1. To achieve an optimal zero order delivery profile,the orifice must be smaller . 2. The typical orifice size in osmotic pumps ranges from 600µ to 1 mm. 25
    26. 26. D. Membrane 1. Type and nature of polymer  polymer that is permeable to water but impermeable to solute can be selected  Ex. cellulose esters such as cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose propionate, cellulose acetate butyrate 2. Membrane thickness  release rate from osmotic systems is inversely proportional to membrane thickness 3. Wet strength 4. Water permeability 26
    27. 27. Laser light drilling 27
    29. 29. 7.MARKETED PRODUCTS 1. Products Incorporating ALZA's OROS® Technology A. Cardura® XL (doxazosin mesylate) sold in Germany for the treatment of hypertension. B. Covera-HS® (verapamil) a Controlled Release system for the management of hypertension and angina pectoris. C. Sudafed® (pseudoephedrine) for 24-hour relief of cold and other respiratory allergies. D. Procardia XL® (nifedipine) extended-release tablet for the treatment of angina and hypertension. 2.Products Incorporating ALZA's DUROS® Implant Technology A. Viadur® (leuprolide acetate implant) delivers leuprolide continuously for 12 months. 29
    30. 30. 8. CURRENT ISSUES 1. Microporous bilayer osmotic tablet for colon-specific delivery . 2. Development and evaluation of push-pull based osmotic delivery system for pramipexole  offer significant patient benefits by providing enhanced efficacy and reduced side effects and may also reduce the number of daily doses compared to conventional therapies. 3. A controlled porosity osmotic pump system with biphasic release of theophylline  The developed system was composed of a tablet-in-tablet (TNT) core and a controlled porosity coating membrane  osmotic agent: sodium phosphate, sodium chloride . 30
    31. 31. 9. Advantages 1. Zero order release 2. High release rate 3. High degree of IVIVC 4. Production scale up is easy 5. Increase efficacy of drug 6. Controlled drug delivery 7. Reduce dosing frequency 31
    32. 32. 10. Disadvantages 1. Expensive 2. Chance of toxicity due to dose dumping 3. Release of drug depends on : - size of drug port - surface area - thickness and composition of membrane 32
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