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2 Introduction Mechanism of drug release Formulation components of an osmotic delivery system Classification of ODDS Factors affecting drug release rate References Content

Osmotic Drug Delivery System:

3 Osmotically controlled drug delivery systems utilize osmotic pressure for controlled delivery of active agent. Osmotic pressure : It is colligative property of solution in which a non-volatile solute is dissolved in a volatile solvent. Osmotic Drug Delivery System

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4 Pure water Semi permeable membrane Aqueous Solution Of osmotic solutes

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6 It is defined as passage of solvent into a solution through semi permeable membrane . It can take place when a concentrated solution is separated from a less concentrated solution by a semi permeable membrane. Osmosis 6

Mechanism of drug release:

7 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.

Formulation components of an osmotic delivery system :

8 Formulation components of an osmotic delivery system The major formulation components of a typical osmotic delivery system include : Drug Osmotic agents Semi permeable membrane

Osmotic agents:

9 Osmotic agents 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.

Osmotic pressure of saturated solution of common pharmaceutical solutes :

10 Osmotic pressure of saturated solution of common pharmaceutical solutes Compound or Mixture Osmotic pressure (atm) Sodium chloride 356 Fructose 355 Potassium chloride 245 Sucrose 150 Dextrose 82 Potassium sulphate 39 Mannitol 38 Sodium phosphate tribasic 36

Semi permeable membrane:

11 Semi permeable membrane Semi permeable membrane has important role in controlling drug release. Membrane must meet several performance criteria-: Polymer must exhibit Sufficient wet strength and water permeability so as to attain water flux rate in the desired range. Reflection coefficient (leakage of solute through membrane) should approach the limiting value of 1 .

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12 Membrane should be biocompatible. e.g. Cellulose esters like cellulose acetate, cellulose acetate butyrate, cellulose triacetate and ethyl cellulose and Eudragits.

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13 Wicking agents -: - It has ability to draw water in to the porous network of a delivery device - E.g. colloidal silicon dioxide, kaolin, titanium dioxide, SLS, low molecular weight (PVP). Pore forming agents -: - These agents are particularly used in the pumps developed for poorly water soluble drugs and in the development of controlled porosity osmotic pumps. - These pore forming agents cause the formation of micro porous membrane. - alkaline metal salts such as sodium chloride, sodium bromide, potassium chloride, potassium sulfate, potassium phosphate, etc.

Classification of ODDS :

14 Classification of ODDS Implantable osmotic pump. Oral osmotic pump. Implantable systems further classified as-: For experimental use For human use

Implantable osmotic pump:

15 Implantable osmotic pump For experimental use -: ALZET- It is a miniature, implantable osmotic pumps for laboratory animals. The pump are used to deliver homogenous solutions or suspensions continuously at a controlled rate for extended period. It consist of Drug reservoir, osmotic sleeve & semipermeable membrane.

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For human use :

17 For human use Duros-: It is a miniature, implantable osmotic pumps for long term , parenteral , delivery of drug in human. It consist of an impermeable, titanium alloy cylinder capped on one end by semi permeable membrane & another end by orifice for drug delivery. Interior of implant contains a polymeric piston that separates from drug reservoir.

Fig : Duros Osmotic pump:

18 Fig : Duros Osmotic pump

Oral osmotic pump:

19 Oral osmotic pump These systems can be further classified as-: Single chamber osmotic system: - Elementary osmotic pump Multi-chamber osmotic systems: - push-pull osmotic pump Miscellaneous: - Controlled porosity osmotic pumps - Osmotic bursting osmotic pump - Effervescent activity-based osmotic systems - OROS- CT - L-OROS

Single chamber osmotic system:

20 Single chamber osmotic system Elementary osmotic pump -: 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.

Schematic diagram of an elementary osmotic pump (a) and a push–pull osmotic pump (b).:

21 Schematic diagram of an elementary osmotic pump (a) and a push–pull osmotic pump (b) . 21

Multi-chamber osmotic systems:

22 Multi-chamber osmotic systems Push-pull osmotic pump: It is modified elementary osmotic pump. It is used to deliver both poorly water soluble & highly water soluble drug at a constant rate. It is resembles a standard bilayer coated tablet. One (upper) layer contains drug (60-80% of tablet wt.) in formulation of polymeric osmotic agent & other tablet excipients. This polymeric osmotic agent has ability to form a suspension of drug in situ when this tablet layer imbibes water. Other layer contains osmotic & colouring agent.

Controlled porosity osmotic pumps:

23 Controlled porosity osmotic pumps To increase the permeability of membrane , two layers of the membrane are applied on pumps. The inner membrane is micro porous membrane, which is made up of cellulosic materials containing some water soluble pore forming agents . Semi permeable membrane covers this layer. When system is placed in an aqueous environment the soluble components dissolve, resulting in microporous membrane which provides greater flux of water into the system .

Fig : Schematic diagram of controlled porosity osmotic pump before and during operation.:

24 Fig : Schematic diagram of controlled porosity osmotic pump before and during operation. 24

Osmotic bursting osmotic pump:

25 Osmotic bursting osmotic pump This system is similar to elementary osmotic pump except the delivery orifice is absent. When it is placed in an aqueous environment, water is imbibed and hydraulic pressure is built up inside until the wall ruptures and the contents are released to the environment. Varying the thickness as well as area of the semipermeable membrane can control release of drug. The system is useful to provide pulsated release of drug.

Fig: Osmotic bursting osmotic pump :

26 Fig: Osmotic bursting osmotic pump

Effervescent activity-based osmotic systems:

27 Effervescent activity-based osmotic systems This is commercially important variation of EOP. Poorly soluble drug may precipitate at the pH of gastric fluid, when such drug is delivered through osmotic pump it may precipitate on the orifice. An effervescent compound ( potassium bicarbonate) can be incorporated to overcome this problem. When delivered from the pump with the drug solution, the bicarbonate reacts with acid in the exterior environment generating carbon dioxide. The expansion of gas dispenses the precipitated drug, and preventing the blockage of the orifice.


28 OROS- CT It is developed by Alza co-operation. It is used as a once or twice a day formulation for targeted delivery of drugs to the colon It consist of an enteric coat, SPM & core. Core consist of two compartments - one compartment consist of drug near to orifice. - Second compartment consist of osmopolymer

Fig. Cross-sectional diagram of OROS CT delivery system:

29 Fig. Cross-sectional diagram of OROS CT delivery system


30 L-OROS Liquid OROS controlled release systems are designed to deliver drugs as liquid formulations. It combine the benefits of extended-release with high bioavailability. These are of two types -: - L-OROS Soft cap - L-OROS Hard cap

L-OROS Soft cap:

31 L-OROS Soft cap The liquid drug formulation is present in a soft gelatin capsule, which is surrounded with the barrier layer, the osmotic layer, and semi permeable membrane. A delivery orifice is formed through these three layers. When the system is in contact with the aqueous environment, water is imbibed & results in the development of osmotic pressure inside the system forcing the liquid formulation to break through the hydrated gelatin capsule shell at the delivery orifice .

L-OROS Hard cap:

32 L-OROS Hard cap It is similar to L-OROS Soft cap . It is consists of a liquid drug layer, a barrier layer, and an osmotic engine but present in a hard gelatin capsule. Then it is coated with SPM.

Fig. Cross-sectional diagram of L-OROS delivery system before and during operation:

33 Fig. Cross-sectional diagram of L-OROS delivery system before and during operation

Factors affecting drug release rate :

34 Orifice size Solubility Osmotic Pressure Factors affecting drug release rate 34

Orifice size :

35 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 (1 mm) , to minimize diffusional contribution to delivery rate. Orifice size 35

Methods to create a delivery orifice:

36 Mechanical drill Laser drill Indentation Use of leachable substances in the semipermeable coating e.g. controlled porosity osmotic pump Methods to create a delivery orifice 36

Laser drill :

37 The tablets in which holes are to be formed are charged in the hopper. The tablets drop by gravity into the slots of the rotating feed wheel and are carried at a predetermined velocity to the passageway forming station The passageway forming station, each tablet is tracked by an optical tracking system. During tracking, the beam is transmitted by the optical tracking mechanism onto the surface of the moving tablets Laser drill 37

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38 It moves with the moving tablets as the mirror oscillates clockwise. The walls of the tablet absorb the energy of the beam and gets heated ultimately causing piercing of the wall thus forming orifice. 38

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39 39

Solubility :

40 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 - Use of wicking agents - Use of effervescent mixtures - Use of cyclodextrin derivatives - Use of alternative salt form Solubility 40


41 There is no requirement for the system to disintegrate for the release of drug to occur. Delivery of drugs takes place in solution form, which is ready for absorption. Delivery rate is independent of pH and outside agitation. The in vivo delivery rate of drug is expected to be same as that in vitro. Due to its zero order release profile it is used in early stages of drug research, such as drug screening, animal toxicology . Advantage 41


42 Special equipment is required for making an orifice in the system. If the coating process is not well controlled there is a risk of film defects, which results in dose dumping. Residence time of the system in the body varies with the gastric motility and food intake. It may cause irritation or ulcer due to release of saturated solution of drug. Limitations 42

Marketed products:

43 Elementary osmotic pump Push-pull osmotic systems Marketed products 43 Brand Name API Efidac 24 Chlorpheniramine Acutrim Phenylpropanolamine Sudafed 24 Pseudoephedrine Brand Name API Ditropan XL ® Oxybutynin chloride Procardia XL ® Nifedipine

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44 Implantable osmotic systems Brand Name API Viadur® Leuprolide acetate Chronogesic™ Sufentanil


45 Parmar NS, Vyas SK ;Osmotic pump –A novel drug delivery system. In: Jain NK, editor. Advances in controlled & novel drug delivery.1 st ed, 2005. Delhi :CBS publishers. p -18-35. Wilson CG, Shah HK ;programmed drug delivery systems & the colon. In: Rathbone MJ, Handgraft J, Lane ME , editor. Modified release drug delivery technology. 2 nd edition, Vol-1, USA :Informa Healthcare , p-329-330 . References 45

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46 Sinko PJ . Nonelectrolyte . In : Sinko PJ editor. Martin’s Physical and Pharmaceutical Science . 5 th ed. Philadelphia : Lippincott Williams and Wilkins ;2006.p.124-137 Lordi NG. Sustained release dosage forms . In : Lachman L, Lieberman HA ,Kaing JL . 3 rd ed. Mumbai :Varghese publishing house ; 1990.p.455

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47 R. K. Verma, D. M. Krishna, S. Garg. Review article on Formulation aspects in the development of Osmotically controlled oral drug delivery systems , J. Control. Release, 79, 7-27; 2002.

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48 Thank you 48

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