OSMOTIC CONTROLLED DRUG DELIVERY SYSTEM

Dr. Muhammad Harris Shoaib

� OSMOSIS AND OSMOTIC PRESSURE

� Osmosis is the spontaneous movement of a solvent from

a solution of lower solute concentration to a solution of

higher solute concentration through an ideal

semipermeable membrane, which is permeable only to semipermeable membrane, which is permeable only to

the solvent but impermeable to the solute. The pressure

applied to the higher-concentration side to inhibit solvent

flow is called the osmotic pressure.

� MECHANISM OF DRUG RELEASE� It involves osmosis of gastrointestinal fluid across the semi permeable membrane at a controlled rate.

� Dissolution of drug & osmotic agent to produce a saturated drug solution within a tablet core. saturated drug solution within a tablet core.

� As the no. of molecules in solution increases, the osmotic pressure within a tablet core increases.

� Outer coating (semi permeable membrane) is rigid.

� Therefore to reduce the osmotic pressure within the tablet, saturated drug solution is emitted from a tablet core through orifice

� COMPONENT OF OSMOTIC SYSTEM

� Drug

� Osmotic Components

� Osmotic components usually are ionic compounds consisting Osmotic components usually are ionic compounds consisting of either inorganic salts or hydrophilic polymers.

� These materials maintain a concentration gradient across the membrane.

� They also generate a driving force for the uptake of water and assist in maintaining drug uniformity in the hydrated formulation.

� Salts such as sodium chloride, potassium chloride, or sulfates of sodium or potassium and lithium.

� Sugars such as glucose, sorbitol, or sucrose or inorganic salts of carbohydrates

� Hydrophilic polymers encompass osmopolymers, osmogels, or hydrogels

� The polymers may be formulated along with poly(cellulose), � The polymers may be formulated along with poly(cellulose), osmotic solutes, or colorants such as ferric oxide.

� Swellable polymers such as poly(alkylene oxide), poly(ethylene oxide), and poly (alkalicarboxymethylcellulose) are also included in the push layer of certain osmotic systems

� Hydrogels such as Carbopol (acidic carboxypolymer), Cyanamer (polyacrylamides), and Aqua-Keeps (acrylatepolymerpolysaccharides composed of condensed glucose units such as diester cross-linked polygluran) may be used

� Semipermeable membrane forming polymers

� Important role in controlling drug release

� Must exhibit sufficient wet strength and water permeability so as to attain water flux rate in the desired rangerange

� Impermeability to the passage of drug and other ingredient present in the compartment

� Should be inert and maintain its dimensional integrity to provide a constant osmotic driving force during drug delivery

� Cellulosic polymers such as cellulose ethers, cellulose esters, and cellulose ester-ethers, e.g. are cellulose acylate, cellulose diacylate, cellulose triacylate, cellulose acetate, cellulose diacetate, and mono-, di-, and tricellulosealkanylates

� Other polymer materials such as lightly cross-linked polystyrene derivatives, semipermeable cross-linked poly(sodium styrene sulfonate), and semipermeable poly (vinylbenzyltrimethyl ammonium chloride) may be considered

� Emulsifying agents

� Usually surfactant such as polyoxyethylenated castor oil, polyoxyethylenated sorbitan tristearate, or polyoxyethylenated sorbitan monopalmitate containing different proportions of ethylene oxide. different proportions of ethylene oxide.

� The emulsion initially consists of an oil phase, obtained from vegetable, mineral, or animal origin, in which the hydrophobic drug is dissolved

� Flux regulating agents

� To regulate the permeability of the fluid by incorporating flux-regulating agents in the layer

� Hydrophilic substances such as polyethethylene glycols (300 to 6000 Da), polyhydric alcohols, polyalkyleneglycols, likely to improve the flux

� hydrophobic materials such as phthalates substituted with an alkyl or alkoxy (e.g., diethyl phthalate or dimethoxyan alkyl or alkoxy (e.g., diethyl phthalate or dimethoxyethylphthalate) tend to decrease the flux

� Insoluble salts or insoluble oxides, which are substantially water-impermeable materials, also can be used for this purpose

� Plasticizers

� Gives the flexibility to semipermeable membrane

� Phthalates (dibenzyl, dihexyl, or butyl octyl),

triacetin, epoxidized tallate,o r tri-isoctyl trimellitate

are used

� Filler, Lubricant and Glidant

� FACTOR INFLUENCING THE DRUG RELEASE MECHANISM

�Orifice Size� To achieve an optimal zero-order delivery profile, the crosssectional area of the orifice must be smaller than a maximum size Smax to minimize drug delivery by diffusion through the orifice. Furthermore,The area must be sufficiently large, above a minimum size � The area must be sufficiently large, above a minimum size Smin, to minimize hydrostatic pressure buildup in the system. Otherwise, the hydrostatic pressure can deform the membrane and affect the zero-order delivery rate.

� Therefore, the cross-sectional area of the orifice So should be maintained between the minimum and maximum values. Typically, a diameter of about 0.2 mm through a membrane of 0.2-mm thickness is needed to maintain a delivery rate on the order of 10 mg/h for water-soluble compounds

� Solubility

� Release rate from the osmotic system depend on the solubility of the drug compound

� Swellable polymers or surfactant such as β-cyclodextrinsare added for improving the drug delivery of poorly are added for improving the drug delivery of poorly soluble drugs from osmotic system

� Osmotic pressure

� The osmotic pressure directly affects the drug release rate

� To achieve a zero-order release rate, it is essential to keep π constant by maintaining a saturated solute solution.

� Osmotic pressure enhanced by adding osmotic agents

� Semipermeable membrane

� Must be permeable to water and not to ions

� Release rate is independent of the pH of the environment

� The drug dissolution takes place inside the system and not in the environmentin the environment

� CLASSIFICATION OF OSMOTIC PUMP

� Osmotic delivery system for solids

� Type I: Single Compartment System

� It consist of an osmotic core containing drug & if required osmotic agent , which is coated with semi permeable osmotic agent , which is coated with semi permeable membrane .

� When core imbibes water osmotically at a controlled rate through semi permeable membrane , forming a saturated drug

� solution.

� The system delivers, via orifice, saturated drug solution

� Elementary Osmotic pump System is the common example

Elementary Osmotic Pump

System

� Type II: Multiple Compartments

� Modification of Elementary pump system

� Based on bi-layer and tri-layer tablets consisting of a push layer (which is drug free and other layer containing drug

� These multilayered tablets are again coated with semi permeable membrane into which a small orifice for drug permeable membrane into which a small orifice for drug released has been drilled

� The push layer contain osmotic active agent and water swellable polymers

� The drug layer contains the drug, osmotically active excipients and suspending agents

� Mechanism of release based on

� Water from the GI tract will enter the system leading to

� Swelling of the push layer

� Formation of liquid suspension of the drug into the drug layer

The expansion of push layer will then lead to the drug � The expansion of push layer will then lead to the drug release in suspended form into the GI tract.

� Drug should be dissolved after release from the push pull system

� Push Pull system is the common example of Multi-compartment system

Push Pull System (Multi compartment system)

� Example of Push Pull system

� Procardia XL (Indomethacin)

� Ditropan XL (Oxybutynin chloride)

� Dynacirc CR (Israpidine)

� Glucotrol XL (Glipizide)

� Covera HS (Verapamil HCl)

� Concerta (Methylphenidate)

� Osmotic Delivery System for Liquids� Active ingredients in liquid form are difficult to deliver from controlled release platforms because they tend to leak in their native form.

� Therefore, liquid active agents typically are enclosed in a soft gelatin capsule, which is surrounded by an osmotic soft gelatin capsule, which is surrounded by an osmotic layer that, in turn, is coated with a semipermeablemembrane.

� When the system takes up water from its surroundings, the osmotic layer squeezes the innermost drug reservoir. The increasing internal pressure displaces the liquid from the system via a rupturing soft gelatin capsule.

Osmotic Delivery System for Liquids

� ADVANTAGES OF OSMOTIC CONTROLLED DRUG DELIVERY SYSTEM

� Independence of Release rate on Hydrodynamics

� Independence of Release on pH� Independence of Release on pH

� Diffusing species is only water

� Invitro and invivo correlation more predictable

� Suitable for wide ranges of drugs

� Typically give zero order profile

� DISADVANTAGES OF OSMOTIC DRUG DELIVERY SYSTEM

� Costly manufacturing process

� Limited selection of excipients and polymers � Limited selection of excipients and polymers appropriate membrane and core tablet design

� Integrity and consistency of coating is essential