Osmotic drug delivery systems : Osmotic drug delivery systems PRESENTED BY
K.VINOD REDDY
(M.PHARM) CEUTICS
SRI VASAVI INSTITUTE OF PHARMACEUTICAL SCIENCES 1
contents : contents Definition
Introduction
Release kinetics
Mechanism of drug release
Factors affecting drug release rate
Types of osmotic pumps
Advantages & disadvantages of ODDS
Applications of ODDS
Conclusion
References 2
OSMOSIS : OSMOSIS Osmosis can be defined as the net movement of water across a selectively permeable membrane driven by a difference in osmotic pressure across the membrane.
It is driven by a difference in solute concentrations across the membrane that allows passage of water, but rejects most solute molecules or ions.
Osmotic pressure : It is the pressure which, if applied to the more concentrated solution, would prevent transport of water across the semi permeable membrane. 3
Formula : Formula Π = p c RT
Where,
p = Osmotic pressure
Π = osmotic coefficient
c = molar concentration
R = gas constant
T = Absolute temperature 4
Introduction : Introduction Solutions of different concentrations having the same solute and solvent system exhibit an osmotic pressure proportional to their concentrations. Thus a constant osmotic pressure, and thereby a constant influx of water can be achieved by an osmotic delivery system that results in a constant zero order release rate of drug.
Osmotic pressure is used as driving force for these systems to release the drug in controlled manner.
These systems can be used for both route of administration i.e. oral and parenterals. Oral osmotic systems are known as gastro-intestinal therapeutic systems (GITS). Parenteral osmotic drug delivery includes implantable pumps. 5
Release Kinetics: : Release Kinetics: The osmotic drug delivery system consists of
an osmotic core containing drug
an osmogen surrounded by a Semi permeable membrane with or without an aperture.
The rate of delivery generally follows the zero order kinetics and declines after the solution concentration falls below saturation.
The solute delivery rate from the system is controlled by solvent influx through the semi permeable membrane 6
Equation : Equation (Q/t) z = Pw Am/ hm (πs-πe )
(Q/t)z= Rate of zero order drug release.
Pw= water permeability
Am= effective surface area
hm= thickness of semi permeable membrane
πs= osmotic pressure of saturated solution of
osmatically active drug or salt in system.
πe = osmotic pressure of GI fluid. 7
Mechanism of drug release : 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 8
Factors effecting drug release rate : Factors effecting drug release rate Orifice size :
The size of the orifice must be larger than a minimum size (600µ), to minimize hydrostatic pressure.
This is necessary step in achieving zero order drug release.
The size of the orifice must be smaller than a maximum size (1mm), to minimize diffusional contribution to delivery system
Eqn : Smin = 5 [(L/Pmax)μ(dV/dt)]
Smin = minimum size of the orifice
dV/dt = volume of flux through an orifice
L = length of the orifice
μ = viscosity of the drug solution flowing through the orifice
Pmax = maximum tolerated hydrostatic pressure difference across the membrane before occurrence of deformation of the housing 9
Osmotic pressure : Osmotic pressure The next controlling factor that must be optimized is the osmotic pressure between inside compartment & external environment
To achieve a zero-order release rate, it is essential to keep constant osmotic pressure by maintaining a saturated solute solution
Osmotic agents are added that enhance osmotic pressure 10
solubility : solubility The release rate depends on the solubility of the solute inside the drug delivery system.
Therefore, drugs should have sufficient solubility to be delivered by osmotic delivery.
Various solubility modifying approaches include
Use of swellable polymers
wicking agents
effervescent mixtures
cyclodextrin derivatives
alternative salt form
The fraction drug release with zero order kinetics given by :
F(z) = 1 – S/P
where,
F(z) = fraction release by zero order
S = drug solubility in g /cm3
P = density of core tablet 11
Membrane type : Membrane type Entry of water depends on nature & type of membrane used for formulation
Example : Cellulose ester, Cellulose Triacetate, Cellulose Propionate, Cellulose acetate butryrate,ethyl Cellulose & Eudragits
Other factors include :
Level of pore formers incorporated into the wall
The drug load in the core 12
Properties of the drugs used in odds : Properties of the drugs used in odds Short biological half-life {2-6 hr }
Highly potent drug
Required for prolonged treatment
Eg : Nifedipine
Glipizide
Verapamil
Chlorpromazine hcl 13
Type of Osmotic Pumps : Type of Osmotic Pumps 14 IMPLANTABLE Osmotic Pumps ORAL Osmotic Pumps
Slide 15: 15 Type of Implantable Osmotic Pumps
Rose-Nelson Osmotic Pump : Rose-Nelson Osmotic Pump 16 Rose and Nelson developed the first osmotic pump in 1955.
The Osmotic pump was having three chamber
Water to be loaded prior to use was the drawbacks of rose nelson osmotic pump.
The pumping rate of Rose-Nelson pump is given by the equation:
dm/dt = dv/dt *c
Where:
dm/dt = Drug release rate.
dv/dt = Volume flow of water into salt chamber.
c = Concentration of drug into drug chamber. Drug Chamber Elastic Diaphragm Salt Chamber Rigid Semi permeable membrane Delivery orifice Water Chamber
Higuchi Leeper Osmotic Pump : Higuchi Leeper Osmotic Pump 17 It represents the first simplified version of Rose-Nelson pump.
It contains a rigid housing and the semi permeable membrane, which is supported on a perforated frame.
Rigid housing is divided in two chambers by a movable separator.
It has a salt chamber containing saturated soln of MgSO4 with excess MgSo4 and Drug chamber. Rigid housing Movable seperator Membrane perforated frame Drug chamber salt chamber
Higuchi Theeuwes Osmotic Pump : Higuchi Theeuwes Osmotic Pump 18 In early 1970s, Higuchi and Theeuwes developed a simpler form of Rose-Nelson Pump.
Semi permeable wall itself acts as a rigid outer casing of the pump.
The device is loaded with drug prior to use.
alzet osmotic pump : alzet osmotic pump Design: Empty reservoir within the core of the pump is filled with the drug or hormone solution to be delivered and is surrounded by salt chamber with impermeable layer between them.
Mechanism: Water enters into the salt chamber through semipermeable membrane and causes compression of flexible reservoir and delivery of drug solution.
Application: To deliver drugs, hormones, and other test agents continuously at controlled rates from one day to six weeks. 19
Mini Osmotic Pump (ALZET) : Mini Osmotic Pump (ALZET) 20 In vivo
Slide 21: 21 Push Pull
Elementary Osmotic Pump : 22 Elementary Osmotic Pump Rose Nelson pump was further simplified in the form of elementary osmotic pump by Theeuwes in 1975.
It is fabricated as a tablet coated with SPM
Normally EOP deliver 60 – 80 % of its content at constant rate.
It has short lag time of 30 – 60 minute.
LIMITATION: -
SPM should be 200-300μm thick to withstand pressure
Thick coatings lowers the water permeation rate
Applicable mostly for water soluble drugs
Osmotic Pump for Insoluble drugs : 23 Osmotic Pump for Insoluble drugs For Insoluble Drugs Composition:
Particles of osmotic agents are coated with an elastic semipermeable membrane.
These coated particles are then mixed with insoluble drug & tabletted & coated with rigid semipermeable membrane in usual way.
Drug Release:
When this system is placed in water it imbibes into the osmotic agent and they get swelled & delivers insoluble drug out of orifice. Insoluble Drug
Water
Osmotic agent coated with elastic SPM
Controlled Porosity Osmotic Pump : 24 Controlled Porosity Osmotic Pump It is not laser or micro driven orifice hence advantageneous over other osmotic system.
The semi permeable coating membrane contains water-soluble pore forming agents.
Example like NaCl, KCl, and Urea.
Such formed pores becomes permeable for both water and solutes.
The rate of flow dv/dt of water into the device can be represented as
dv / dt = Ak / h (Dp-DR)
Where:-
k = Membrane permeability
A = Area of the membrane
Dp = Osmotic pressure difference
DR = Hydrostatic pressure difference
Push pull osmotic pump : Push pull osmotic pump They contain two or three compartment separated by elastic diaphragm.
Upper compartment contain drug with or without osmogen (drug compartment nearly 60 – 80 %) and lower compartment (Push compartment) contain Osmogen at 20 – 40 %.
Example ProcardiaXL for Nifedipine 25
Monolithic Osmotic System : 26 Monolithic Osmotic System Dispersion of water soluble drug is made in a polymeric matrix and compressed as tablet.
Tablet is then coated with semi permeable membrane.
When MOS comes in contact with aqueous environment, the water penetrates in the core and forms a saturated solution of component which will generate osmotic pressure which results in the rupturing of membrane of polymeric matrix surrounding the agent. Thus liberating drug to move outside the environment.
MOS is simple to prepare but the system fails if more than 20 – 30% volume of active agent is incorporated in device because above this level it leads to leaching of substance
Slide 27: 27 COATING THICKNESS WEIGHT VARIATION DISSOLUTION FRIABILITY PORE DIAMETER IN VIVOEVALUATION THICKNESS HARDNESS Evaluation
Advantages : Advantages The delivery rate of zero-order is achievable with osmotic systems.
Delivery may be delayed or pulsed, if desired.
Higher release rates are possible with osmotic systems compared with conventional diffusion-controlled drug delivery systems.
The release rate of osmotic systems is highly predictable and can be programmed by modulating the release control parameters.
For oral osmotic systems, drug release is independent of gastric pH and hydrodynamic conditions.
The release from osmotic systems is minimally affected by the presence of food in gastrointestinal tract.
A high degree of in vivo- in vitro correlation (IVIVC) is obtained in osmotic systems. 28
Slide 29: 29
Marketed formulations : Marketed formulations 30
Marketed formulations : Marketed formulations 31
Applications of ODDS: : Applications of ODDS: Theeuwes (1985) developed elementary osmotic pump(EOP) for metoprolol and oxprenolol for once daily administration
For the desired solubility succinate salt of oxprenolol and fumarate salt of metoprolol were used along with sodium bicarbonate as osmotic agent.
Vyas (1995) designed elementary osmotic pump, push-pull osmotic pump and diffusion pump of ciprofloxacin HCI using empty gelatin capsule shell.
The extent of drug release was found in the decreasing order of push-pull osmotic pump (80%), elementary osmotic pump (60%) and diffusion pump (45%). 32
Conclusion : Conclusion Osmotic system technology has been extended to allow rate-controlled, constant drug delivery.
These systems made 4- and 3-times-a-day regimens obsolete.
Instead they made once-a-day dosing practical for many agents.
For these and other reasons, the future of osmotic technology in drug delivery is bright 33
References : References Lachman L., Liberman H. A., Kanig J. L., The theory and practise of industrial pharmacy. 2nd Edition 1991, Varghese publishing house
Aulton M. E., pharmaceutics the science of dosage form design. 2nd Edition 2002, Churchill livingstone,
Novel drug delivery system , volume 50, Y.W.Chien
Indian Journal of Novel Drug delivery 2(4), Oct-Dec, 2010, 122-131 34
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Slide 36: 36 THANK YOU