Osmotic drug delivery system

Detail information regarding Osmotic drug delivery system

1. Osmotic drug delivery system Presented by: Mrunal More M.Pharmacy ( Pharmaceutics Dept ) AISSMS College of Pharmacy Pune. 1

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3. Contents: INTRODUCTION CONCEPT OF OSMOSIS PRINCIPLES OF OSMOSIS BASICS COMPONENTS CLASSIFICATON OF ODDS FACTORS INFUENCING THE DESIGN OF ODDS EVALUATION PARAMETERS OF ORAL ODDS ADVANTAGES DISADVANTAGES LIMITATION MARKETED PRODUCTS HISTORICAL ASPECTS REFERENCES 3

4. INTRODUCTION T he rate and extent of absorption of drug from conventional dosage forms may vary greatly depending on factors such as presence of excipients, physicochemical properties of the drug, various physiological factors such as presence or absence of food, pH of gastro intestinal tract, gastro intestinal motility and so on . Uncontrolled rapid release of drug may cause local gastro intestinal or systemic toxicity . Hence , various approaches are made in designing the formulations, which will overcome the disadvantages of conventional dosage forms , which include sustained/controlled drug delivery system . There are three main classes of controlled-release drug delivery system ; transdermal, intravenous, and oral systems  . Oral osmotically controlled release (CR) delivery systems exploit osmotic pressure for controlled delivery of active agents   . Drug release from these systems is independent of pH and other physiological parameters to a large extent and it is possible to modulate the release characteristics by optimizing the properties of drug and system  . Alza Corporation R of USA was the first to develop an oral osmotic pump. 4

5. CONCEPT OF OSMOSIS Osmolarity : Osmolarity is the number of osmoses per liter of solution . Osmolality : Osmolality is the number of osmoses per Kg of water . Osmosis : Osmosis refers to the process of association of solvent molecules from lesser concentration to higher concentration across a semi permeable membrane. Osmotic Pressure : Osmotic pressure is a colligative property of a solution in which the scale of osmotic pressure of the solution is self governing on the number of separate entities of solute present in the solution. Osmotic pressure produced due to imbibitions of fluid from external atmosphere into the dosage form regulates the delivery of drug from osmotic device. Speed of drug release from osmotic pump is straightly proportional to the osmotic pressure developed due to imbibitions of fluids by Osmogens . 5

6. PRINCIPLE It is based on the principle of osmotic pressure . Osmotic pressure is a colligative property , which is dependent on concentration of solute that contributes to osmotic pressure. Solutions of different concentrations having the same solvent and solute system show an osmotic pressure proportionate to their concentrations . Thus a constant osmotic pressure, and thereby a constant influx of water can be achieved by an osmotic drug delivery system . This results a constant zero order release rate of drug . The rate of drug release from osmotic pump depends on the osmotic pressure of the core and the drug solubility; hence, these systems are suitable for delivery of drugs with moderate water solubility. Osmotic pressure is proportionate to temperature and concentration and the relationship can be described by following equation. π = n 2  RT Where, π = osmotic coefficient n 2  = molar concentration of solute in the solution R = gas constant T = Absolute temperature  6

7. BASIC CONCEPT: Osmotic drug delivery devices are composed of an osmotically active drug core , which is surrounded by a rate controlling semipermeable membrane . Osmotic drug delivery system differ from diffusion based systems in that the way of delivery of the active agents is driven by an osmotic gradient somewhat than the concentration of drug in the device . In the most simple type of osmosis-controlled drug release the following sequence of steps is involved in the release process: 1 .Osmotic transport of liquid in to release unit. 2 .Dissolution of drug within the release unit. 3. Convecting transport of a saturated drug solution by pumping of the solution through a single orifice through pores in the semi permeable membrane 4 . 7

8. BASICS COMPONENTS OF ODDS 8

9. SEMIPERMEABLE MEMBRANE HYDROPHILIC & HYDROPHOBIC POLYMERS WICKING AGENTS : A wicking agent is defined as a material with the ability to draw water into the porous network of a delivery device. A wicking agent is of either swellable or nonswellable nature. SOLUBILIZING AGENTS SURFACTANTS OSMOGEN/ OSMOTIC AGENT COATING SOLVENT PLASTICIZERS PORE-FORMING AGENT : These agents are particularly used in the pumps developed for poorly water soluble drug and in the development of controlled porosity or multiparticulate osmotic pumps. These poreforming agents cause the formation of microporous membrane . FLUX REGULATOR DRUG 9

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12. CLASSIFICATION OF ODDS Implantable Osmotic Pump Oral Osmotic Pump 12

13. IMPLANTABLE OSMOTIC PUMP 13

14. 1. Rose and Nelson Pump In the year 1955, these two Australian physiologists reported the first osmotic pump to the gut of sheep and other cattle . The pump is constructed of three chambers viz., a drug chamber with an orifice, a salt chamber with elastic diaphragm containing excess solid salt, and a water chamber . A semipermeable membrane separates the drug and water chamber . The difference in osmotic pressure across the membrane moves water from the water chamber into the salt. The volume of chamber increases because of this water flow, which distends the latex diaphragm separating the salt and drug chambers, there by pumping drug out of the device . 14

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16. 2. Higuchi- Theeuwes PumP In the early 1970 Higuchi- Theeuwes developed a similar form of Rose-Nelson pump as shown in the figure . The semipermeable wall itself acts as a rigid outer casing of the pump. The device is loaded with drug prior to use. When the device is put in an aqueous environment the release of the drug follows a time course set by the salt used in the salt chamber and the permeability of the outer membrane casing. 16

17. 3.Higuchi-Leeper pump The Higuchi- Leeper pump is modified version of RoseNelson Pump . It has no water chamber, and the device is activated by water imbibed from the surrounding environment . The pump is activated when it is swallowed or implanted in the body . This pump consists of a rigid housing, and the semipermeable membrane is supported on a perforated frame . It has a salt chamber containing a fluid solution with excess solid salt. Recent modification in Higuchi- Leeper pump accommodated pulsatile drug delivery. The pulsatile release was achieved be the production of a critical pressure at which the delivery orifice opens and releases the drug 17

18. Implantable miniosmotic pump They are may be used in experimental animals or in human being. DUROS ® technology : Provides a bicompartment system separated by a piston . One of the compartments consists of osmotic engine specifically formulated with an excess of solid NaCl , such that it remains present throughout the delivery period and results in a constant osmotic gradient . It also consists of a semi permeable membrane on one end through which water is drawn into the osmotic engine and establishes a large and constant osmotic gradient between the tissue water and the osmotic engine. Other compartment consists of a drug solution with an orifice from which the drug is released due to the osmotic gradient . This helps to provide site specific and systemic drug delivery when implanted in humans. The preferred site of implantation is subcutaneous placement in the inside of the upper arm. The delivery period ranges from some days to 1 year. 18

19. 2. ALZET miniosmotic Pumps Are miniature, implantable pumps used for research in animals like mice, rats etc . These infusion pumps continuously deliver drugs, hormones and other test agents at controlled rates from one day to six weeks without the need for external connections or frequent handling which eliminates the need for repeated night time or weekend dosing . ALZET pumps can be used for systemic administration for targeted drug delivery when implanted subcutaneously or intraperitoneally . ALZET pumps operate by osmotic displacement . An empty reservoir within the core of the pump is filled with the drug or hormone solution to be delivered, which is isolated from the chamber containing salt by a semi permeable membrane. Due to the presence of a high concentration of salt in a chamber surrounding the reservoir, water enters the pump through the semi permeable layer. The entry of water increases the volume in the salt chamber, causing compression of the flexible reservoir and delivery of the drug solution into the animal via the exit port . 19

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23. 23 1.PUSH-PULL OSMOTIC PUMP 2. CONTROLLED POROSITY OSMOTIC PUMP

24. 24 3 . MONOLITHIC OTS 4.OROS CT

25. 25 5 . SOTS 6. L-OROS

26. 26 7.Bursting osmotic pump Ruptured film Solid core Film coat 8.Multiparticulate delayed Release system

27. FACTORS INFUENCING THE DESIGN OF ODDS: 27

28. Drug solubility: For the osmotic system, solubility of drug is one of the most essential parameters affecting drug release kinetics from osmotic pumps. Drugs with a density of unity and the solubility ≤ 0.05 g/cm3 would be released with ≥ 95% zero order kinetics Semi Permeable Membrane : Some of the membrane variables that are significant in the devise of oral osmotic system are: Cellulose acetate, cellulose dilacerate, cellulose triacetate, cellulose propionate, cellulose acetate butyrate, ethyl cellulose and eudragits . Type and Nature of Polymer :Any polymer porous to water but impermeable to solute can be selected. Membrane Thickness : Thickness of the membrane has a perceptible result on the drug discharge from osmotic system , which is inversely relative to each other . It is helpful in the Evaluation of OSCDDS . Type and Amount of Plasticizer : In pharmaceutical coatings, low molecular weight diluents are added to change the physical properties and get better film-forming individuality of polymers. Visco elastic performance of polymers significantly. In particular, plasticizers can turn a hard and fragile polymer into a softer, more flexible material and possibly make it more resistant to automatic stress. These changes also affect the permeability of polymer films. Size of Orifice :Size of delivery orifice must be optimized to manage the drug release from osmotic system. The size of the delivery orifice must be lesser than a maximum size to minimize drug delivery by diffusion through the orifice. 28

29. EVALUATION PARAMETERS OF ODDS 29

30. ADVANTAGES OF ODDS They typically give a zero order release summary after an initial lag. Deliveries may be belated or pulsed if preferred. Drug discharge is free of gastric pH and hydrodynamic state. The release mechanisms are not dependent on drug . A high quantity of in-vitro and in-vivo correlation ( IVIVC ) is obtained in osmotic systems. The release from osmotic systems is modestly affected by the presence of food in gastro intestinal tract. The release rate of osmotic systems is highly expected and can be planned by modulating the release control parameters. 30

31. DISADVANTAGES OF ODDS Special equipment is necessary for making an orifice in the system . It may cause irritation or ulcer due to release of soaked solution of drug. Dose dumping . Retrieval therapy is not possible in the case of unpredicted adverse events. Expensive. If the coating process is not well controlled there is a danger of film defects, which outcome in dose discarding. Size hole is dangerous . 31

32. LIMITATION OF ODDS It may cause irritation or ulcer due to release of soaked solution of drug. Extraordinary equipment is necessary for creating the orifice in the system. Habitation time of the system in the body varies with the gastric motility and food eating. 32

33. Marketed product: 33

34. Historical aspects of osmotic pump: 34

35. CASE STUDY : ( https :// www.sciencedirect.com/science/article/pii/S0168365900002431 ) Nifedipine controlled delivery by sandwiched osmotic tablet system Abstract The sandwiched osmotic tablet system (SOTS), which is composed of a sandwiched osmotic tablet core surrounded by a cellulose acetate membrane with two orifices on both side surfaces, has been successfully prepared with the purpose of delivering nifedipine . The sandwiched osmotic tablet core consists of a middle push layer and two attached drug layers. Influences of tablet formulation variables, orifice size and membrane variables on nifedipine release of SOTS have been studied. It was found that potassium chloride amount of push layer and polyethylene oxide amount of drug layer had markedly positive effects on nifedipine release. A push layer/drug layer co-controlled osmotic delivery mechanism and the optimal core formulation have been proposed. The appropriate orifice size was observed in the range of 0.50–1.41 mm. It was also found that the drug release rate of SOTS could be increased by incorporating hydrophilic plasticizer in the membrane, whereas it decreased with hydrophobic plasticizer. It has been observed that the SOTS gives fairly comparable in vitro release features as that of commercialized push–pull osmotic tablet system, such as an approximately constant rate up to 24 h and independence of release media and agitation rate. Exempting side identification before drilling, it is easier to prepare the SOTS than the push–pull osmotic tablet system. 35

36. 36 THANK YOU FOR YOUR ATTENTION ANY QUESTIONS ?