![• When a single osmotic driving agent is used, thepumping rate of the osmotic
device of (volume per unit time) is define by
Q/t=Pw Sm [𝜸m (𝛑s−𝛑e )(∆𝐏d+∆𝐏e)]
• Pw is permeability of semi permeable membrane to water
• Sm is effective surface area of the membrane
• 𝛾m is osmotic reflection coefficient of the membrane
• Πs and πe are the osmotic pressure of saturated solution of osmotic driving agent
and of the environment where device is located, respectively.
• ∆Pd is elevation of internal pressure generated in the drug formulation
compartment as the result of water influx into osmotic agent compartment
• ∆Pe is pressure required to deform drug formulation compartment inward
• If the net osmotic pressure gradient [𝜸m (𝛑s−𝛑e )] is constant and the hydrostatic
pressure(∆𝐏d+∆𝐏e) is negligibly small, can be simplified to
Q/t=Pw Sm [𝜸m (𝛑s−𝛑e )](https://image.slidesharecdn.com/odss-copy-231220090648-0235c825/85/Osmotic-Drug-Delivery-System-and-basic-components-of-Osmotic-system-8-320.jpg)
Osmotic Drug Delivery System and basic components of Osmotic system
- 1. SUBJECT:DDS(DRUG DELIVERY SYSTEMS) Academic year 2023-24 Prepared by: Miss. Dhanashree R. Davare M.Pharm First Year Roll No-03 Department of Pharmaceutics Guided By: Dr. Sachin.S.Mali Professor and Head, Department of Pharmaceutics. ASHOKRAO MANE COLLEGE OF PHARMACY, PETH VADGAON TITLE OF SEMINAR:OSMOTIC ACTIVATED DRUG DELIVERY SYSTEM Shri Balasaheb Mane Shikshan Prasarak Mandal Ambap’s
- 2. CONTENTS 1. Introduction 2. Advantages 3. Disadvantages 4. Principle Of Osmosis 5. Basic Components Of Osmotic System 6. Osmotic Pumps
- 3. Introduction ➢Osmotic pressure is used as the driving force for osmotic to release the drug in a controlled manner. ➢Osmotic controlled drug delivery system generally consist of a core including the drug an osmotic agent ,excipients and semipermeable membrane coat. ➢Osmotic pressure gives zero order drug delivery which is driven force for release of drug from dosage form. ➢ODDS work on the principle osmosis i.e movement of water across a semipermeable membrane driven by a difference in solute concentration across the membrane which create difference in osmotic pressure across the membrane. ➢ ODDS is driven by an osmotic gradient differ from diffusion based system that activate agent are deliver by concentration of drug in the device
- 4. ADVANTAGES OF ODDS 1. It gives zero order release profile after an initial lag. 2. Drug release is independent of gastric pH,GI motility and hydrodynamic condition. 3. Release of drug in highly predictable rate and rate is also programmable by modulating the release control parameters 4. Enhanced bioavailability of drug and reduced interpatient variability. 5. Decrease dosing frequency 6. Improve patient compliance
- 5. DISADVANTAGE OF ODDS • Dose dumping • Expensive • Rapid Development of tolerance • Hypersensitivity reaction may occur • Integrity and consistency are difficult
- 6. PRINCIPLE OF OSMOSIS • Osmosis refer to the process of movement of solvent from lower concentration of solute towards higher concentration of solute acrossa semipermeable membrane • Abbe Nollet first reported osmotic effect in 1748,but Pfeffer in 1877 had the pioneer of quantitative measurement of osm otic effect. • Pfeffer measured the effect by utilizing a membrane which is selectively permeable to water but impermeable to sugar .The membrane separated sugar solution from pure water. Pfeffer observed a flow of water into the sugar solution that was halted when a pressure p was applied to the sugar solution Pfeffer postulated that this pressure, the osmotic pressure π of the sugar solution is proportional to the solution concentration and absolute temperature • Van’t Hoff established the analogy between the Pfeffer results and the ideal gas laws by the expression 𝝅 = 𝒏𝟐𝑹𝑻 • Where,n2 represent the molar concentration of sugar(or)other solute) in the solution,R represent the gas constant and T the absolute temerpature.
- 7. • Another method of obtaining a good approximation of osmotic pressure is by utilizing vapour pressure measurements and by using expression. 𝝅 = 𝐑𝐓𝐈𝐧(Po/P)/v • Where Po represent the vapour pressure of the pure splvent,P is the vapour pressure of the solution and v is the molar volume of the solvent .As vapour pressure can be measured with less effort than osmotic pressure this expression is frequently used. • Osmotic pressure for soluble solutes is extremely high .This high osmotic pressure is responsible for high water flow across semipermeable membrane. • The rate of water flow by osmotic pressure can be given by following equation. dV/dt=A𝜽𝝅/𝒍 • Where dV/dt represents the water flow across the membrane area A and thickness l with permeability 𝜃. • ∆𝜋 depicts the difference in osmotic pressure between the two solution on either side of the membrane.
- 8. • When a single osmotic driving agent is used, thepumping rate of the osmotic device of (volume per unit time) is define by Q/t=Pw Sm [𝜸m (𝛑s−𝛑e )(∆𝐏d+∆𝐏e)] • Pw is permeability of semi permeable membrane to water • Sm is effective surface area of the membrane • 𝛾m is osmotic reflection coefficient of the membrane • Πs and πe are the osmotic pressure of saturated solution of osmotic driving agent and of the environment where device is located, respectively. • ∆Pd is elevation of internal pressure generated in the drug formulation compartment as the result of water influx into osmotic agent compartment • ∆Pe is pressure required to deform drug formulation compartment inward • If the net osmotic pressure gradient [𝜸m (𝛑s−𝛑e )] is constant and the hydrostatic pressure(∆𝐏d+∆𝐏e) is negligibly small, can be simplified to Q/t=Pw Sm [𝜸m (𝛑s−𝛑e )
- 9. BASIC COMPONENTS OF OSMOTIC SYSTEM ❖DRUG • Drug should have short half-life (2-6 hrs),highly potent and used for prolonged treatment. Solubility of drug should be moderate i.e not be very high or very low. • Drugs such as DiltiazemHCL, Carbamazepine,Metoprolol, Oxprenolol,Nifedipine, Glipizide,verapamil are some example for osmotic drug delivery system. ❖OSMOTIC AGENT • This agent is also called as osmogens or osmogents and has a function to create osmotic pressure inside the system. • If the solubility of drug is low then the drug will show slow rate zero order release. The osmotic agent is used to enhance the release rate by creating a very high osmotic pressure gradient inside the system. • Different type of osmogents are categorized as water-soluble salts of inorganic acids e.g. magnesium chloride or sulfate lithium, sodium, or potassium chloride; sodium or potassium hydrogen phosphate, potassium or sodium chloride etc,
- 10. • water-soluble salts of organic acids e.g. sodium and potassium acetate, magnesium succinate, sodium benzoate, sodium citrate, sodium ascorbate etc and carbohydrates e.g. mannose, sucrose, maltose, lactose,etc. ❖SEMIPERMEABLE MEMBRANE • Semi Permeable Membrane is made up of polymer that permeable to water but impermeable to solute (drug and excipients). These polymers are cellulose esters, cellulose ethers and eudragits. • Cellulose esters are cellulose acetate, cellulose dilacerate, cellulose triacetate, cellulose acetate butyrate, cellulose propionate. Cellulose acetate is a commonly employed and available in different acetyl content grades like 32% and 38% which are widely used. Acetyl content is the average number of hydroxyl groups on the anhydro glucose unit of the polymer replaced by substituting group also called degree of substitution (DS). • semipermeable membrane must have sufficient wet strength and wet modules (10-5 Psi) so that it retains its dimensional integrity throughout the operational lifetime of the device. The water flux rates are estimated by water vapour transmission rates through membrane. Semipermeable membrane must exhibit sufficient water flux rates (dv/dt) in the desired range. The reflection coefficient (a) or "leakiness" of the osmotic agents should approach the limiting value of unity. But polymer membranes must be more permeable to water.
- 11. OSMOTIC PUMPS ❖SINGLE CHAMBER OSMOTIC PUMP(ELEMENTARY OSMOTIC PUMP) • Elementary osmotic pump contained osmotic core consist of drug with or without an osmogens. Then coated with a semipermeable membrane (SPM) and a small orifice is created in the membrane for release • When such a system is swallowed water from the GIT enters through the SPM when come in contact with GI fluid because of the osmotic pressure gradient and forms a saturated solution inside the device. Water enter continues at a constant rate until the entire solid drug inside the tablet has been dissolved. • This increases the hydro static pressure inside the tablet and forces the soaked drug solution through the oral cavity present in the membrane. Drug continues to be delivered at a declining rate until the osmotic pressure between outside environment and saturated drug solution getting nearly same. The elementary osmotic pump delivers 60-80% of its drug content at a constant rate. • There is a short lag time of 30- 60 min since the system hydrates before zero order drug release from the elementary osmotic pump is obtained.
- 12. • Elementary osmotic pump are mostly suitable for moderate water soluble drug. Factors which affecting the release rate from elementary osmotic pump are membrane thickness, osmotic pressure, type of membrane and characteristics, solubility, size of the delivery orifice.
- 13. ❖OSMOTIC PUMP WITH NON-EXPANDING SECOND CHAMBER • It has multi-chamber devices comprise of systems containing a non-expanding second chamber. Depending on the function of second chamber it is divided into two sub groups. Purpose of second chamber is either dilution of drug solution exit or immediate delivery of two d • In first device the second chamber is used to dilute the drug solution, beneficial for relatively insoluble drugs since saturated solution of such drug irritate GI tract. Two rigid chambers are present in this device, one for biologically inert osmotic agent and another for the drug. • Water is entering through the surrounding semipermeable membrane into two chambers. • The solution of osmotic agent formed in the first chamber then passes through the connecting hole to the drug chamber where it mixes with the drug solution before exiting through the micro porous membrane that form a part of wall surrounding the chamber.
- 14. Fig:OSMOTIC PUMP WITH NON-EXPANDING SECOND CHAMBER
- 15. ❖MULTICHAMBER OSMOTIC PUMP PUSH-PULL OMOTIC PUMP(PPOP) • The PPOP was developed by Alza Corporation, consists of two compartments which are separated by an elastic diaphragm. Out of these two compartments first or upper compartment also called drug compartment contains the drug mixed with osmotically active agents and another is lower compartment used as push compartment contains the polymeric osmotic agents. • Upper compartment has an orifice to deliver drug outside the pump. The drug layer has 60-80% weight of total weight, while the osmotic polymer layer has 20- 40%. When the device comes in contact with water, both compartments are imbibed with water. • There is no orifice present to lower compartment, osmotic agent in layer simultaneously attract water, it expands volumetrically with entry of water in it and pushes the diaphragm into the upper chamber and delivering the drug solution/suspension via the delivery orifice. • This pump is useful in deliver greatly water-soluble and water insoluble drugs.
- 16. Fig:MULTICHAMBER OSMOTIC PUMP PUSH-PULL OMOTIC PUMP(PPOP)
- 17. ❖OROS-CT SYSYEM • OROS-CT is used as a once or twice a day formulation for targeted delivery of drug to the colon. • OROS-CT system can be a single osmotic unit or it may have 5-6 push-pull units enclose within a hard gelatin capsule. Hard gelatin capsule shell dissolves after taking the capsule in stomach Each unit is with enteric coating prevents entry of gastric fluid in lower compartment. As pH increase coating start to dissolve and PPOP is imbibed with intestinal fluid . The drug is delivered out of the orifice at a rate controlled by the rate of water transport transversely the membrane.
- 18. ❖SANDWITCH OSMOTIC TABLETS(SOTS) • It is with two delivery orifices each for two drug layers and between these layers polymeric push layer is sandwiched. • When placed in the aqueous environment the middle push layer containing the swelling agent swells and the drug is released from the two orifices situated on opposite sides of the tablet. • Because of this SOTS are applicable for drugs which are prone to cause local irritation of the gastric mucosa.
- 19. ❖MODIFICATION OSMOTIC PUMPS CONTROLLED POROSITY OSMOTIC PUMPS(CPOP) • Controlled porosity osmotic pump tablet contains core filled with water soluble additives and drug which coated with asymmetric structure membrane. • Membrane is semipermeable and insensitive pore forming additive, like sodium chloride, urea, and potassium chloride, mannitol, and sorbitol, dispersed throughout the wall. • CPOP when come in contact with aqueous environment dissolved water soluble additive from membrane are leached out forms permeable to water. It forms sponge like structure which act as microporous membrane and has controlled porosity walls (5 to 95% pores with a pore size from 10A-100μm), substantially permeable to both water and dissolved drug agents. • The release of drug takes place through these micro porous channels. The release rate of drug delivery is dependent on the coating thickness, level of soluble components in the coating, permeability of the semi permeable membrane, solubility of the drugin the tablet core, and osmotic pressure difference across the membrane, total surface area of coating.
- 20. • The release rate of drug delivery is not affected by the pH and agitation of the release media. • The rate of flow dv/dt of water into the device can be represented as dv/dt = Ak/h (Dp-DR) • Where, k is Membrane permeability, A is Area of the membrane, Dp is Osmotic pressure difference, DR is Hydrostatic pressure difference. • The CPOP has an advantage that it reduce stomach irritation problem by releasing drug from the whole surface of device. Controlled porosity osmotic pump tablet can be made as very small by coating appropriate membrane. No complicated laser drilling is not required to form orifice. • The CPOP is suitable for delivery of drugs having intermediate water solubility and limits of water solubility by some modifications
- 21. Fig:MODIFICATION OSMOTIC PUMPS CONTROLLED POROSITY OSMOTIC PUMPS(CPOP)
- 22. ❖LIQUID OROS CONTROLLED RELEASE SYSTEM(L-OROS) • Liquid OROS are designed to deliver drugs as liquid formulations and combine the benefits of extended release with high bioavailability. They are of three types of system, first is LOROS hard cap, which consists hard gelatin capsule with two parts that is liquid drug layer and an osmotic engine, and coated with semipermeable membrane. • Second is L OROS soft cap in which liquid drug formulation filled in soft gelatin capsule which is enclosed in barrier layer called as osmotic layer and finally all layers covered with release rate-controlling membrane. • Third one is delayed liquid bolus delivery system in capsule shaped device meant for deliver a pulse of liquid drug. • The delayed liquid bolus delivery system comprises three layers which are a placebo delay layer, a liquid drug layer and an osmotic engine, all surrounded by rate controlling semi permeable membrane. The delivery orifice is drilled on the placebo layer after osmotic engine is expands, the placebo is released first through orifice and delaying release of the drug layer from 1to 10 hour.
- 23. • Hydrostatic pressure is increased by imbibing water inside across semi permeable membrane results in growth of the osmotic layer thereby forcing the liquid formulation through the delivery orifice out of hydrated gelatin capsule shell. It is appropriate for controlled delivery of lipophilic drugs. Fig:LIQUID OROS CONTROLLED RELEASE SYSTEM(L-OROS)
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