§ Semi-permeable membrane : § Criteria 1. Adequately wet strength and permeability.2. Should be nontoxic and inflexible. 3.
Should beadequately thick to withstand the pressure of device. 4. Any which is spongy to water but impermeable to solute can be used as a coating substance .
e.g.; Cellulose acetate,cellulose triacetate and ethylcellulose. § Hydrophilic polymers : CMC, HPMC, HEC § Wicking agent : SLS , PYP , Bentonite § Solubilizing agent : PVP ,CP , PEG § Osmogens : Nacl , KCl § Plasticizer : Phathaltes , benzoates , TEC § Flux regulator :Polypropylene , polybutylene § Pore forming agent : Calcium nitrate , Potassium sulphate § Coatingsolvent : acetone and methanol(80:20) , acetone and water (90:10) § Surfactants : poly oxyethylenatedcastor oil Factors that affectthe drug release from osmoticdelivery of drugs: The drug delivery fromosmotic delivery device relyon various process and formulation aspects .
Apart from the water miscibility of the drug, the solubility of the further fundamentalingredients can also have main impact on the drug delivery by producing an osmotic pressure gradient crosswise thepolymeric layer on interaction with dissolution medium. The rate of drug release from osmotic pumps rely on the total solubility and theosmotic pressure of the drug. Many features thatinfluence the release of drug from osmotic system are follows: Orifice Size: Osmotic drug delivery apparatus comprises of at least one delivery orifice in the semipermeable membrane for drug deliveryand the diameter of delivery orifice should be optimized inorder to regulate the drug release from osmoticsystems . To obtain an suitable zero-order delivery profile, the area of the orifice should be reducedthan a size Smax to minimum drugdelivery by diffusion through orifice.
Moreover, the area must be adequately large, abovea minimum size Smin, to lessen the hydrostatic pressure build up in the device. Else, the hydrostatic pressure can break the membrane and influences the zero-order release rate of drug. Therefore, the cross sectional area of the orifice must be maintained between minimum andmaximum values. Solubility: The deliveryrates of drug rely on the solubility ofthe solute inside the drug delivery device. Subsequently, drugs should have adequate solubility to be delivered by osmotic deliveryon the other hand, most water-soluble drugs would revealed high delivery ratethat would be zero-order for a small percentage of the initial drug load. In the case of low solubility compounds, various otherapproaches may be applied and can be divided into two categories. First, swell- able polymers can be added that gives in the delivery of poorly soluble drugs in the form of a suspension. Second,the drug solubility can be altered by using different techniques.
Semi permeable Membrane: The selection of a rate-controlling membrane is an significant characteristicin the formulation design of osmotic systems. Drug release from osmotic systems is not influenced by pH andagitational force of the gastrointestinal tract to a greater degree because of the reason that selectively water permeable membrane andoperative isolation of dissolution from the gut environment. The thickness of membrane is kept between 200 and 300 mm· Use of encapsulated excipients: Acapsule device layered with unevenmembranes to transport drugswith poor water-solubility .For instance , solubility of a poorlywater-soluble drug such as glipizide was increased by using bicarbonate, it was employed as encapsulated excipients (pH-controlling excipients) in the capsule device. The solubility modifier (meglumine), in the form of mini-tablets, was coated with a rate controlling membrane to delay its availability inside the core. Thus, the solubility of glipizide was improved to its delayed release from the device.
· Use of cyclodextrin derivatives: These enhances the drugsolubility and dissolution through addition of complexation or solid dispersion which behave as hydrophilic carriersfor drug with inadequate molecular aspects for complexation, or as tablet dissolution enhancer for drug with high dose, with mixture of a drug/cyclodextrin Complex isproblematic, eg, paracetamol. The same phenomenon can also beemployed for the osmotic systems · Use of Swell-able polymers:Polyethylene oxide, vinyl acetatecopolymer have even swelling rate which causes drug release at constant rate.Also, the pressure build up while swelling doesnot rupture the system · Use of wicking agents: Theseagents may improve the surface area of drug along with aqueous fluids. E.g.Sodium lauryl sulfate and colloidal silicon dioxide, etc. Ensotrol® technology works on the same principle for drugadministration via osmotic system.· Use of effervescent mixture: It can be new tactic to deliver poorly water-soluble drugsfrom osmotic delivery systems.
After administration, the effervescent mixture having drug is deliveredunder pressure via delivery hole in the membrane Effervescent mixture of citric acid and sodium bicarbonate produces carbondi-oxide which build up pressure in the osmotic system and finally release the drug at steady rate · Co-compression of drug with excipients: Different excipients can beused to alter the solubility of drugs with mechanisms likesaturation solubility, pH dependentsolubility. For instance, such excipients are organic acids, buffering agent, etc. · Useof alternative salt form: Change in salt form of drug may improve solubility. It is observed that the salt of drug is too soluble to maintain a saturated solution and thus zero order release for the estimated delivery life ofdosage form.
Afterwards osmotic pump is designed with this salt form that give extendedrelease up to 24 h.· Resin Modulation approach:Ion-exchange resin methods are frequently used to alter the solubility ofdrugs.Some of the resins used in osmotic systems are Poly (4-vinyl pyridine), Pentaerythritol, citric and adipic acids. Classification of OsmoticDDS Osmotic Drug Delivery Devices fall in two categories: · Implantable:1 Implantable osmotic pump2 Oral osmotic Pump 1.Implantable osmotic pump 2 Oralosmotic pump A )Single chamber osmoticpump: B).Multi chamber osmotic pump C) Modified osmotic pump 1.
Oralosmotic pump A. the Rose and Nelson pump: Origin: This drugdelivery system was initially designed by the Australian scientists Rose and Nelson, in 1955 when they wereadministering drug to thesheep and cattle gut Components This drug delivery system contains threechambers 1 .Drug chamber 2. Salt chamber holding salt bridge 3.
Water chamber4. Semi permeable membrane Working Semipermeable divides the salt and water compartment as thewater enters from water to salt chamber due to gradient build up by osmotic pressure the salt chamber extends and forces the drug chamber . Drug comsout of the orifice and finally pumped from the DDS to the diseased area.B. Higuchi Leeper osmotic pump This DDS is the advancement of Rose and Nelson pump, in its design in a way thatit has no water chamber.Components 1 Saltchamber 2 Drug chamber3 Semi permeable membrane 4 A rigid housing Working As is has no water chamber so through the of imbibitionmethod drug enters the system and activates it .
On implantationof device the biological liquid presentin the environment enters the salt chamber which comprises of the fluid solution , on enteringbiological fluidabsorbs MgSO4 andbuild up a osmotic pressure that inturn forces the movable partition towardsdrug chamber and drug comes out of the orifice Modification Through this systempulsatile delivery is accomplished. Pressure is the criticalfactor .This is done by drilling the orifice with stretching elastic material upto the specific concentration pressure build up openthe orifice and drug is delivered one more time after drug releasepressure reduces and orifice getclosed. Application: This system is employed in veterinary for administration of antibiotics and growthhormones in animals.
C. HighuchiTheeuwes osmotic pump This drug delivery device is a further advancementof Rose and Nelson pump in 1970.This system is changed inworking with respectto previous one ina way that semi permeable membrane is present in rigidhousing. Components 1.
Salt chamber 2. Drug chamber 3. Rigid housing 4.Semipermeable membrane Working This device also works on imbibition of water into system here membrane is strong enough to endure highpressure. Drug is loaded prior to the application in this way this device is used for longer period of time giving the delayed release.
Drugdelivery is governed by the salt in the salt chamber and permeability aspects of the cell membrane. D. Implantable mini-osmotic pumps Osmotic pump working on this principle was Azlet pump designedby Azlet Corporation in 1976. They are small and compact mini-osmotic pumps.Application For implantable in–vivo controlled studieswhere delayed drugis required. For the loss of drug by diffusion delivery port is made in a longitudinal position 2. Single chamber osmotic pump: Elementary osmotic pump: New drug delivery device, basic Oros systemwas described byTheeuwes in 1975.It is a major controlledrate device.
Components 1. Laser drilled semi permeablemembrane 2. Osmotic core Working Controlis present inside the water thatsurrounds the formulating agent. Tablet comprises of osmotic core having drug and laser drilled holes semi permeable membrane. On administration water absorbs into the system and drug dissolution occurs and the drug solution is diffused in a controlled manner at constant rate by osmosis .This replaced the drug in the core and drug is released from orifice . This DDS promotes zero order reaction. Drawback Onlysuitable for water soluble drugs Multi chamber osmotic pump: Push pull osmotic pump: Itis a modification of EOP,used for poorly water soluble and water soluble drugs at a steady rate; resemblance with bi-layered coatedtablet.
Components 1. Two layers ( functionally different)2. Semi permeable Working Upper layer has drug osmogen, second layerconsists of polymeric agent, coloring agents and excipients then tablet issurrounded by laser drilled holes. Polymeric system will form a suspension of drug insitu. When the system encounters with GIT fluid the polymeric osmotic layer swells up and release the drug to the external environment .
via orifice in a fine dispersion Osmotic pump with non-expanding second chamber It is further classified into two types. Components 1. Two layers2. Porous semi permeablemembrane.
Working In the first type, second chamber aids in dilution of drug solution This is beneficial because some drugs cause theirritation when they are saturated. In second type, there are two chambers, onecomprises of the osmotic agent and the other comprises of the drug. Osmotic agentsolution is made which enters the drug solution andthen their mixture is pumpedout by means of semipermeablemembrane present surrounding the chamber.
Specifictypes Controlled porosity osmotic pump Components1. Laser drilled Semi permeable membrane 2. Two layers Working It is anosmoticdevice wherein thedelivery holes are molded in situthrough leaching of water solublepore-forming agents merged in semipermeable membrane (E.g., urea, nicotinamide, sorbitol, etc.). Drugrelease rate from controlled porosity osmotic pump relies on various factors like layering thickness, level ofleachable pore-forming agent(s)solubility of drug in tablet core, and the osmotic pressure difference.
Advantage Lessen the stomach irritation, as drug is delivered from the whole of the device surface instead of from a single hole. Moreover, no complex laser-drilling unit is necessarybecause the delivery orifices are designed in situ Osmotic bursting osmotic pump: This system aids in pulsatile release Modification This systemhas resemblance to an elementary osmotic pump instead it lacks delivery orifice and size is smaller. On placing in angastric fluids, water is absorbs and hydraulic pressure isdeveloped within membrane sothat the semipermeable membrane ruptureand the drug is released to the environment.
By altering the thickness as wellas the area of semipermeable membrane can be regulated and in turn release of drug. Liquid OralOsmotic system: It is used for liquid drug formulations. A liquidformulation is specifically suitable for delivering insoluble drugs andmacromolecules such as polysaccharides and polypeptides. Molecules require external liquidcomponents to aid in solubilization, dispersion, protection from enzymatic degradation, and promotion of gastrointestinal absorption.COMPONENTS 1. 3 layers2. Semipermeable membrane 3. Soft gelatincapsule Working This device comprises of first is rate controlling membrane, second is osmotic layer and third is soft gelatin capsule.
During process, water permeates across the rate controlling membrane andcauses swelling of the osmotic layer resulting in todevelopment of hydrostatic pressure in the system which expels the liquidformulation out of the delivery orifice. Sandwiched osmotic tablet (SOT)Components 1. 2 layers 2.
Semipermeable membrane Working Polymeric pushlayer sandwiched between two drug layers with two delivery holes. When placed in the aqueous environment, the middle push chamber containing the swelling agents’ swells and the drug is delivered from the two orifices located on alternating sides of the tablet.Advantage 1. To avoid local irritation of stomach. Delayed Delivery Osmotic device: Because ofsemi permeable walls, an osmotic device fundamentally show lag time before drug delivery begins. No doubt this characteristic is usually considered as adisadvantage, it can be used beneficially. The delayed release of certain drug(drugs for early morning asthma or arthritis) may be helpful. Telescopic Capsulefor Delayed Release: Components 1.
Two chambers 2. Exit port 3. Waxy separation 4. Semipermeable membrane Working This device contains three chambers, the firstchamber has drug and an exit port, and the secondconsists of an osmotic engine .A layerof wax like material actas partition in between twolayers. To connect the delivery device, the active agent is inserted into one of the sections by manual ormechanical fill process.
The bilayer tabletwith the osmotic engine is inserted into a completed cap part of the capsule with the convexosmotic layer projected in to the closed end of the cap and the barrier intothe closed end of the cap and the barrier layer uncovered towards the cap opening. The open end of the loaded vessel is fitted into the open end of the cap, and the two pieces are pressedtogether until the cap, osmotic bilayer tablet and vessel fit together firmly. When fluid is absorbed in the device, the osmotic engine swells and apply pressure on the movable connected first and second wall sections. During the delay period the volume of reservoir having activeagent is kept continuous and steady,therefore a slight pressure gradient exists between the outer surrounding andinternal side of the reservoir.
As a result, the flow of environmental fluidcompelled by the pressure enter the reservoir is minimal and subsequently noagent is carried for the period