RATE CONTROLLED DRUG DELIVERY SYSTEM

1. OSMOTIC AND ENZYMATIC DRUG
DELIVERY SYSTEM
SUBMITTED BY:-
ARAVINDA D
1ST SEM M PHARM
Dept of pharmaceutics
V . V. Puram college of pharmacy
Bangalore-70
SUBMITTED TO:-
Dr. KALAVATHY D J
Professor dept of
pharmaceutics
V.V. Puram college of
pharmacy
Bangalore-70
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2. CONTENTS
INTRODUCTION
PRINCIPLE
FORMULATION CONSIDERATIONS
CLASSIFICATION OF ODDS
ENZYME ACTIVATED DRUG DELIVERY SYSTEM
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3. INTRODUCTION
 Osmotic systems are the most reliable controlled drug delivery systems
(CDDS) and can be employed as oral drug delivery systems.
 Osmotic pressure is used as the driving force in ODDS to release the drug
a controlled manner.
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4. Osmosis :-
It refers to the process of movement of solvent from lower
concentration of solute towards higher concentration of solute across the
semipermeable membrane.
Osmotic pressure:
The pressure exerted by the flow of water through a semipermeable
membrane separating two solutions with different concentrations of solute.
 These systems can be used for both route of administration i.e. oral and
parenteral. 4

5. PRINCIPLE OF ODDS:-
 ODDS works on the principle of osmosis. i.e. movement of water across a
selectively permeable membrane driven by a difference in osmotic
across the membrane.
 On the basis of this principle osmotic drug delivery gives better drug
not depends on concentration of drug and better results than any other
controlled release system.
 The mechanism in this involves ,when exposed to water, semipermeable
membrane permeable to water into the core , causes dissolution of soluble
the core, and pumping of the solution out of the orifice taken place.
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6. For the drug delivery system containing a solution formulation, the intrinsic rate
of drug release is defined by,
𝑸
𝒕
=
𝑷𝒘𝑨𝒎
𝒉𝒎
𝝅𝒔 − 𝝅𝑬
For the drug delivery system containing a solid formulation, the intrinsic rate of
drug release is defined by ,
𝑸
𝒕
=
𝑷𝒘𝑨𝒎
𝒉𝒎
𝝅𝒔 − 𝝅𝑬 Sd
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7. Where,
 Q/t - rate of drug release
 Pw - permeability of semipermeable housing
 Am -effective of semipermeable housing
 hm - thickness of semipermeable housing
 (π s - π e ) – Differential osmotic pressure b/w DDS with osmotic pressure πs & environmental
osmotic pressure πe
 Sd – Aqueous solubility of drug contained in the solid formulation.
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8. ADVANTAGES:-
 They typically give a zero order release profile after an initial lag.
 Drug release is independent of gastric pH and hydrodynamic condition.
 Decrease dosing frequency.
 Increased safety margin of high potency drugs.
 Drug release from the OCODDSs exhibits significant in vitro-in vivo
correlation [IVIVC] within specific limits.
 Release rate of drug is highly predictable and programmable.
 Enhanced bioavailability of drug.
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9. DISADVANTAGES:-
 It is Highly expensive.
 If the coating process is not well controlled there is a risk of film defects,
which results in dose dumping.
 Retrieval of therapy is not possible in the case of unexpected adverse event
 Rapid development of tolerance.
 Release of drug depends on : -
• size of drug port
• surface area
• thickness and composition of membrane
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10. FORMULATION OF ODDS
 Drugs
 Semipermeable membrane
 Osmogenes
 Polymers
 Solubilizing agents
 Plasticizers
 Wicking Agents
 Coating Solvents
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11. DRUGS :-
 Drugs should have short half life (2-6 hrs.),highly potent and used for
prolonged treatment
 Solubility of drug should be moderate i.e. not very high or very low.
Ex:- Diltiazem HCL , Metoprolol , Glipizide , Verapamil ,etc.….
SEMIPERMEABLE MEMBRANE:-
SPM must possess certain performances criteria:-
 It must be sufficient wet strength and wet modules.
 This membrane should be more permeable to water.
 It should be sufficient thick to withstand the pressure within the device
 It is made up of polymer hence that is permeable to water but impermeable
solute(drug and excipients)
Ex:- Cellulose Acetate, Cellulose Triacetate and Ethyl Cellulose.
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12. OSMOGENS OR OSMOTIC AGENTS:-
 These are used to achieve the constant osmotic pressure in the compartment.
 These are classified into two types:-
a) Water soluble salts of inorganic acids
Ex:- Magnesium chloride, potassium or sodium chloride , sodium or
potassium hydrogen phosphate etc…
b) Water soluble salts of organic acids
Ex:- Sodium and potassium acetate , magnesium succinate , sodium
benzoate, sodium citrate etc…
c)Carbohydrates
Ex:-mannose, sucrose , maltose, lactose etc…
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13. POLYMERS:-
These are used for making drug containing matrix core.
Ex:- Hydrophilic polymers are hydroxy ethyl cellulose, carboxy
methylcellulose,
hpmc etc.…
Hydrophobic polymers are ethyl cellulose wax materials etc..
SOLUBILIZING AGENTS:-
Agents that inhibits crystal formation of the drugs .
Ex:- PVP, PEG, and Cyclodextrin
A high HLB surfactant, particularly anionic surfactants (e.g., Tween 20,
60, 80, long chain anionic surfactants such as SLS)
Plasticizers:-
Permeability of membranes can be increased by adding plasticizer,
which increases the water diffusion coefficient.
Ex:-PEG , phthalates, benzoates, etc.. 13

14. WICKING AGENTS:-
It helps to draw water to surfaces inside the core of the tablet, thereby
creating channels or a network of increased surface area.
Ex:-SLS, PVP, bentonite etc..
COATING SOLVENTS:-
Used for manufacturing the walls of the osmotic device.
Ex:-acetone and methanol 80:20,
acetone and water 90:10
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15. CLASSIFICATION OF OSMOTIC PUMP
They are generally classified onto two types:-
 Implantable osmotic drug delivery system
 Rose nelson pump
 Higuchi leeper osmotic pump
 Higuchi theeuwes osmotic pump
 Oral osmotic drug delivery system
 Elementary osmotic pump
 Multi chamber osmotic pump
.expandable
.non expandable
 Push pull osmotic pump
 Sandwiched osmotic pump
 Controlled porosity osmotic pump
 Multi particulate delayed release
 Mono lithic osmotic system 15

16. ROSE NELSON PUMP:-
 The first osmotic pump developed in 1955 for the delivery of drugs to the sheep
and cattle gut
 It composed of three chambers water, salt and drug chambers.
 The difference in osmotic pressure across the membrane moves water from the
water chamber in to the salt chamber.
 The volume of chamber increases because of this water flow, which distends the
latex diaphragm separating the salt and drug chambers, thereby pumping drug
out of the device.
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17. Higuchi leeper osmotic pump
 It has no water chamber, and the activation of the device occurs after
imbibition of the water from surrounding environment.
 Widely employed for veterinary use. It is either swallowed or implanted in
body of an animal for delivery of antibiotics or growth hormones to animal.
Porous Membrane Support MgSO4 Movable Separator Drug Chamber Rigid
Housing Satd. Sol. Of MgSO4. Solid MgSO4 Semi-permeable Membrane.
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18. Higuchi theeuwes osmotic pump:-
 When this pump is exposed to water, the core imbibes water osmotically at a
controlled rate, determined by the membrane permeability to water and by the
osmotic pressure of the core formulation.
 As the membrane is non expandable, the increase in volume caused by the
imbibition of water leads to the development of hydrostatic pressure inside the
tablet.
 This pressure is relieved by the flow of saturated solution out of the device
through the delivery orifice.
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19. Elementary osmotic pump
• It is fabricated as a tablet coated with semi permeable membrane, usually
cellulose acetate
• When this coated tablet is exposed to an aqueous environment, the osmotic
pressure of the soluble drug inside the tablet draws water through the
semipermeable coating and a saturated aqueous solution of drug is formed
the device. The membrane is non- extensible and the increase in volume due to
inhibition of water raises the hydrostatic pressure inside the tablet, eventually
leading to flow of saturated solution of active agent out of the device through a
small orifice.
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20. PUSH PULL OSMOTIC PUMP
 It is a modification of EOP, it can delivered both poorly water soluble and highly water
soluble drugs at a constant rate.
 When the system is placed in aqueous environment, water is attracted into the tablet by
an osmotic agent in both the layers. The osmotic attraction in the drug layer pulls water
into the compartment to form in situ a suspension of drug.
 The osmotic agent in the nondrug layer simultaneously attracts water into that
compartment, causing it to expand volumetrically, and the expansion of nondrug layer
pushes the drug suspension out of the delivery orifice .
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21. SANDWICHED OSMOTIC PUMP
 It is composed of polymeric push layer sandwiched between two drug layers with two
delivery orifices.
 When placed in the aqueous environment, the middle push layer containing the swelling
agents' swells and the drug is released from the two orifices situated on opposite sides of
the tablet
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22. CONTROLLED POROSITY OSMOTIC PUMP:-
 It is an osmotic tablet wherein the delivery orifices (holes) are formed in situ through
leaching of water soluble pore-forming agents incorporated in semipermeable membrane
(SPM)
 Drug release rate from CPOP depends on various factors like coating thickness,
solubility of drug in tablet core, level of leachable pore-forming agent(s) and the osmotic
pressure difference across the membrane.
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23. MARKETED PRODUCTS OF OSMOTIC DRUG DELIVERY SYSTEM
Products Incorporating ALZA's OROS® Technology
A. Cardura® XL (doxazosin mesylate) sold in Germany for the treatment of
hypertension.
B. B. Covera-HS® (verapamil) a Controlled Release system for the
of hypertension and angina pectoris.
C. C. Sudafed® (pseudoephedrine) for 24-hour relief of cold and other
respiratory allergies.
D. D. Procardia XL® (nifedipine) extended-release tablet for the treatment of
angina and hypertension.
Products Incorporating ALZA's DUROS® Implant Technology
A. Viadur® (leuprolide acetate implant) delivers leuprolide continuously for 12
months.
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24. ENZYME ACTIVATED DRUG DELIVERY SYSTEM
 This type of biochemical system depends on the enzymatic process to activate
release of drug.
 Drug reservoir is either physically entrapped in microspheres or chemically
bound to polymer chains from biopolymers (albumins or polypeptides).
 The release of drug is activated by enzymatic hydrolysis of biopolymers
(albumins or polypeptides) by specific enzyme in target tissue.
 Ex. Albumin microspheres release 5-fluorouracil in a controlled manner by
protease – activated biodegradation.
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25. REFERENCES
 zahidenzymeactivatedandosmoticpressureactivateddrugdelivery-
180315151005.pdf
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407637/
 https://www.researchgate.net/publication/313161177_OSMOTIC_DRUG_DELIVE
RY_SYSTEMS/link/5891a24b458515aeac940f59/download
 A text book for DDS by Prafull P
.Patil ,BHUSHAN P Gayakwad, Dr Surajj Sarode
 INTERNET SOURCE
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