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 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. 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 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), 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 (acrylate polymerpolysaccharides 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 range 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 tricellulose alkanylates 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. 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, polyalkylene glycols, likely to improve the flux hydrophobic materials such as phthalates substituted with an alkyl or alkoxy (e.g., diethyl phthalate or dimethoxy ethylphthalate) 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 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 -cyclodextrins 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 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 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 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 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 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 Multicompartment 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 layer that, in turn, is coated with a semipermeable membrane. 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 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 appropriate membrane and core tablet design Integrity and consistency of coating is essential