Osmatically Controlled Drug Delivery System

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Presented by: Chinchole Pravin Sonu

(M.PHARM 2nd SEM)DEPARTMENT OF PHARMACEUTICS & QUALITY ASSURANCE

R. C. Patel Institute of Pharmaceutical Education and Research, shirpur.

CONTENTIntroduction

Advantages & Disadvantages

Principle of osmosis

General Consideration

Factor affecting drug release rate

Classification

Recent advances & evaluation parameter

Characteristics of osmotic pump

Some commercially marketed osmotic system

References

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Introduction

In recent years, considerable attention has been made on the

development of Novel drug delivery system(NDDS).

Reasons for this are:

Relatively low development cost & time required for introducing

NDDS as compared to New chemical entity(NCE).

In the form of NDDS, an existing drug can get a new life, there by

increasing its market value, competitiveness,& patent life.

Majority of controlled release forms fall in category of matrix,

reservoir, or osmotic system

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Controlled Drug DeliveryThe future of drug delivery

systems will involve smart systemsThese will address the issue of

keeping the drug at the desired therapeutic level in the body thus avoiding frequent administration

Systems use detection of chemical signals in the body to prompt the release of drugs

The ultimate goal is to administer drugs at the right time, at the right dose anywhere in the body with specificity and efficiency

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Osmotically controlled drug delivery system

It can be employed as oral drug delivery system or implantable device.

It utilizes the principle of osmotic pressure for the delivery of drug.

They are also known as GITS(Gastro-intestinal therapeutic system) and today different types of oral osmotic pumps are available.

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Advantages & Disadvantages

• Typically follow a zero order release kinetics.

• Delivery of drug takes place in solution form, which is ready for absorption.

• Improved patient compliance due to reduced dosing frequency.

• Prolonged therapeutic effect with uniform blood concentration.

• Toxicity may occur due to dose dumping.

• Size of hole is critical factor.• Residence time of the system

in the body varies with the gastric motility & food intake.

• Surgery may require for removal of device incase of implantable system.

• Special equipment is required for making an orifice.

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Principle of Osmosis

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Osmosis refers to the process of movement of solvent molecules from

lower conc. to higher conc. across a semipermeable membrane until

there is an equal conc. of fluid on both sides of membrane.

Semipermeable membrane

Equation for drug release rate through orifice

Where:A = the membrane areah = the membrane thicknessLp= the mechanical permeabilityσ= the reflection coefficientπ= the osmotic pressureρ= the hydrostatic pressureC = the concentration of compound in the dispensed fluid

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General consideration Basic components:

Drug Osmotic Agent Semipermeable membrane

Other components:

Hydrophilic/hydrophobic polymers Solubilising agents Surfactants Other common tabletting aids like lubricants, binders, diluents,

glidants etc

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Factors Affecting the Release Rate 1) Drug Solubility : i. Co-compression of drug with excipients: a) Drugs have high water solubility b) Addition of solubility modulating agent c) Use of polymer coated buffer components to modulate the drug

solubility within the core d) Use of buffers,

ii. Use of encapsulated excipients:

iii. Use of effervescent mixtures :

iv. Use of swellable polymers :

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Factors Affecting the Release Rate

2) Osmotic Pressure:

The release of drug is directly proportional to osmotic pressure

3) Size of Delivery orifice:

system should contain at least one delivery orifice

4) Membrane types and characteristics:

It should be biocompatible

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Examples of osmogentsCategory Example ATM

Water-soluble salts of inorganic acids

potassium chloride, Sodium phosphatepotassium phosphate etc.

245 31 105

Water soluble salts of organic acids

Sodium phosphate,Citric acid,

29 82

Carbohydrates fructose, sucrose, lactose etc.

355 150 23

Water-soluble amino acids

Glycine, leucine, alanine, etc.

Organic polymeric osmogents

Sodium carboxy methyl cellulose, HPMC, cross-linked PVP, carbopol, polyacrylamide, etc.

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Classification of osmotic controlled drug delivery system

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Implantable osmotic pump :Rose & Nelson pump:

Consists of three chambers- Drug, salt, & water chamber.Drug & salt chambers are separated by elastic diaphragm where as water & salt chambers are separated by a semipermeable membrane.Osmotic pressure act as a driving force

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Higuchi-Leeper osmotic pump

Rigid housing

Active agent formulation

Movable seperator

Sat. solution of Mgso4

Semipermeable membrane

Porous membrane support

Modified version of Rose & Nelson pump. It consist of only two chambers , water chamber is absent.

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Higuchi-Theeuwes osmotic pump It is another simplest modified version of Rose & Nelson pump. Coating containing osmogen

Delivery orifice

wall of flexible collapsible tube wall of semipermeable membrane

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Implantable mini-osmotic pump (ALZET)ALZET pumps have 3 concentric layers:

Rate-controlling, semi-permeable membrane Osmotic layer Impermeable drug reservoir

ALZET pumps work by osmotic displacement.

Water enters the pump across the outer, semi-permeable membrane due to the presence of a high concentration of osmotic agent in the osmotic chamber. The entry of water causes the osmotic chamber to expand, thereby compressing the flexible reservoir.Deliver the drug solution through the delivery portal.

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Oral osmotic pump(OROS)Elementory osmotic pump:

It is most simplest form of osmotic pump.

It consist of osmotic core containing drug, coated with

semipermeable membrane with delivery orifice.

The core may or may not contain osmotic agent depending on

osmotic activity of drug.

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Push-Pull osmotic pumpIt is modified EOP & used for drugs with very poor water solubility & also for highly water soluble drugs.It is similar to bilayer coated tablet- Upper & Lower layerTablet core is coated by using standerd film coating equipment with a semipermeable membrane.

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L-OROS• To overcome drug solubility problem ALZA developed L-OROS

system.• It is a liquid soft gel product containing drug in dissolved state

initially and then coated with barrier membrane, then osmotic push layer & at last with semi-permeable membrane drilled with an exit orifice.

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Controlled porosity osmotic pump• It consist of two layers of membrane.

• The inner membrane is micro porous containing water soluble pore

forming agent.

• A semi-permeable membrane covers this layer.

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Osmotic bursting osmotic pump

• It is similar to elementary osmotic pump except delivery orifice is absent & size may be small.• When it is placed in an aqueous medium, water is imbibed &

hydraulic pressure is built up inside until the wall ruptures & contents are released to the environment.• Release can be controlled by varying thickness as well as the

area of the semi-permeable membrane. • This system is useful to provide pulsated release.

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Method for preparation orifice

a) Laser drilling

b) Use of modified punches

c) Systems with passageway formed in situ

d) Use of pore formers

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Recent advance work Osmotically driven protein release : e.g., Bovine serum albumin (BSA) prepared using trehalose, NaCl, poly(trimethylene carbonate) and poly(trimethylene carbonate-co-d,l- lactide)

Evaluation parameter

Scanning electron microscopyOsmometer

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Characteristics of Osmotic Pumps Research use Route of

administrationDuration of steady state delivery(hr)

Fill volume(ml)

Steady-state delivery

rate(µl/hr)

Distinguishing terminology

Clinical research Oral 12 0.2 15.0 Oral pump

Clinical research Oral 24 0.2 8.0 Oral pump

Clinical research Rectal/vaginal 30 2.0 60 Rectal pump

Animal research Implant 168 0.2 1.0 Mini-osmotic pump

Animal research Implant 336 0.2 0.5 Mini-osmotic pump

Animal research Implant 168 2.0 10 Osmotic pump

Animal research Implant 336 2.0 5.0 Osmotic pump

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Some commercially marketed osmotic system

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References

• Joseph R. Vincent H., “Controlled drug delivery, fundamentals Applications” , second edition, published by marcel dekker,

published at New York Press , Vol - 29 , 263, 414, 498.

• Yei w. chein, “Novel drug delivery system”, published by Marcel dekker, published at New York Press, Vol - 50, 18-19,142,450.

• S.P.Vyas , R .K. Khar, “ Targated & contrlled drug delivery, Novel carrier system” , CBS publishers & Distributors, 477-499.

• D.M. Brahmankar, S.B. Jaiswal, “ Biopharmaceutics & Pharmacokinetics ” , Vallabh prakashan, 353

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References

• N.K.Jain , “Advances in controlled & novel drug delivery” ,19-37.

• Aditya M. Kaushal and Sanjay Garg , An Update on Osmotic Drug Delivery Patents, Pharmaceutical Technology August 2003,38-44

• Salish sharma , “Osmotic Controlled Drug Delivery “ Pharmainfonet .com Vol 3 issued 3 in 2008.

• Frank Gaebler , Coherent, and Graham Coffee, Laser Drilling Enables Advanced Drug Delivery Systems

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Factors Affecting the Release Rate :

d) development of hydrostatic pressure within the core which may lead to deformation

4-Membrane types and characteristics: The membrane must possess certain performance Criteria: a) Sufficient wet strength and water permeability b) It should be selectively permeable to water c) Should be biocompatible d) Effectively isolating the dissolution process from the gut environment e) The SPM must be 200–300

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2-Osmotic Pressure: a)The release rate of drug from an osmotic system is directly

proportional to the osmotic pressure of the core formulation b)The osmotic pressure gradient between inside the compartment and

the external environment should be optimized to control rate of drug release

c)It is possible to achieve and maintain a constant osmotic pressure by maintaining a saturated solution of osmotic agent in the compartment

3-Size of Delivery orifice: a)Osmotic delivery systems contain at least one delivery orifice in the

membrane for drug release. b)The size of delivery orifice must be optimized in order to control the

drug release from osmotic systems. c)If the size of delivery orifice is too small zero-order delivery will be

affected because of:

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Limitations and Adverse Effects : some cases have been reported regarding the limitations and adverse effects of these types of systems:

�During quality control of nifedipine GITS tablets, it was observed that several batches showed different release patterns of

the drug. Magnetic resonance imaging (MRI) was used to evaluate the GITS

tablets. It was found that non uniform coating around the tablet produce different membrane thicknesses, which was responsible

for differences in release patterns among different batches

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2-Use of encapsulated excipients:a)Solubility of poorly water soluble drug, was improved by incorporation of

encapsulated excipients (pH-controlling excipient) within the capsule device.b)Formulated as mini-tablets, which coated with a rate controlling membrane to

prolong its availability within the core.

3-Use of effervescent mixtures :a)Use of effervescent mixture, can be another approach to deliver poorly water-soluble drugs from osmotic dosage forms b) After administration, the effervescent mixture containing the drug is delivered

under pressure through the delivery orifice in the membrane. Ex of effervescent

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4-Use of swellable polymers :a) Swellable polymers can be utilized for osmotic delivery of drugs having poor aqueous solubility.b) The formulation mainly consists of a compartment, containing the

drug, swelling agents, and osmagents, coated with a rate controlling membrane

c) Vinylpyrrolidone/ vinyl acetatecopolymer and polyethylene oxide were used as swelling agent

d) Uniform rate of swelling of these polymers ensures that the drug is released at a relatively constant rate.

e) Also, the pressure produced during swelling does not lead to rupture of the system.

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MatrixDevices

MembraneDevices

Diffusion-Controlled

Controlled Release Systems

BiodegradableSystems

PendantChain Systems

Chemically-Controlled

Solvent-Activated

Osmotically-Controlled

Swelling-Controlled

Rupture-Controlled

PulsatileDelivery

SinglePulse

OsmoticallyRuptured

PolymerDissolution

PolymerMelting

Multiple Pulse

Electrically-Stimulated

Ultrasonically-Controlled

Magnetically-Controlled

Temperature-Controlled

Ionic-StrengthDependent

pH-Sensitive

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Very rapid gelling and nearly complete hydration of OCAS delivery system in the upper GI tract ensures drug release throughout the entire GI tract,including the colon where water is poorly available. Reprinted from European Urology Supplements, 4(2), Michel MC, Korstanje C, KrauwinkelW, Kuipers M,The pharmacokinetic profile of tamsulosin oral controlled absorption system (OCAS1), pp 15–24, 2005, with permission from European Association ofUrology [8].

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Semipermiable membrane :-

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