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Controlled Release Oral Drug Delivery Systems
Controlled Release Oral Drug Delivery Systems
Professor of Pharmaceutics Department of Pharmaceutics JN Medical College KEL University, Belgaum- 590010, Karnataka, India E-mail: bknanjwade@yahoo.co.in Cell No: 00919742431000
Contents
Overview of Digestive system Introduction Advantages Disadvantages Mechanisms 1.Dissolution 2.Diffusion 3.Combination of Dissolution & Diffusion 4.Osmotic pressure controlled system References
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Digestive System
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Concept
Controlled drug delivery is one which delivers the drug at a predetermined rate, for locally or systemically, for a specified period of time.
Continuous oral delivery of drugs at predictable & reproducible kinetics for predetermined period throughout the course of GIT.
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Advantages
Total dose is low.
Reduced GI side effects. Reduced dosing frequency. Better patient acceptance and compliance. Less fluctuation at plasma drug levels. More uniform drug effect Improved efficacy/safety ratio.
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Disadvantages
Dose dumping. Reduced potential for accurate dose adjustment. Need of additional patient education. Stability problem.
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Dissolution Definition:
Solid substances solubilizes in a given solvent. Mass transfer from solid to liquid. Rate determining step: Diffusion from solid to liquid. Several theories to explain dissolution Diffusion layer theory (imp) Surface renewal theory Limited solvation theory.
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Matrix Type
Also called as Monolith dissolution controlled system. Controlled dissolution by: 1.Altering porosity of tablet. 2.Decreasing its wettebility. 3.Dissolving at slower rate. First order drug release. Drug release determined by dissolution rate of polymer. Examples: Dimetane extencaps, Dimetapp extentabs.
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Soluble drug
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Encapsulation
Called as Coating dissolution controlled system. Dissolution rate of coat depends upon stability & thickness of coating. Masks colour,odour,taste,minimising GI irritation.
Soluble drug
Diffusion
Major process for absorption. No energy required. Drug molecules diffuse from a region of higher concentration to lower concentration until equilibrium is attainded. Directly proportional to the concentration gradient across the membrane.
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Rigid Matrix Diffusion Materials used are insoluble plastics such as PVP & fatty acids. Swellable Matrix Diffusion 1. Also called as Glassy hydrogels.Popular for sustaining the release of highly water soluble drugs. 2. Materials used are hydrophilic gums. Examples : Natural- Guar gum,Tragacanth. Semisynthetic -HPMC,CMC,Xanthum gum. Synthetic -Polyacrilamides.
Matrix system
Rate controlling step:
Diffusion of dissolved drug in matrix.
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Higuchi Equation
Q = DE/T (2A.E Cs)Cs.t)1/2 Where , Q=amt of drug release per unit surface area at time t. D=diffusion coefficient of drug in the release medium. E=porosity of matrix. Cs=solubility of drug in release medium. T=tortuosity of matrix. A=concentration of drug present in matrix per unit volume.
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Reservoir System
Also called as Laminated matrix device. Hollow system containing an inner core surrounded in water insoluble membrane. Polymer can be applied by coating or micro encapsulation. Rate controlling mechanism - partitioning into membrane with subsequent release into surrounding fluid by diffusion. Commonly used polymers - HPC, ethyl cellulose & polyvinyl acetate. Examples: Nico-400, Nitro-Bid
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Reservoir System
Rate controlling steps : Polymeric content in coating, thickness of coating, hardness of microcapsule.
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Osmosis
- Movement of solvent from lower to higher concentration. - The passage of solvent into a solution through semipermeable membrane.
Semipermeable Membrane
Osmotic pressure
It is the hydrostatic pressure produced by a solution in a space divided by a semipermeable membrane due to difference in concentration of solutes.
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Provides zero order release Drug may be osmotically active, or combined with an osmotically active salt (e.g., NaCl). Semipermeable membrane usually made from cellulose acetate. More suitable for hydrophilic drug. Examples: Glucotrol XL, Procardia XL,
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Equation
(Q/t) z = Pw Am/ hm (s-e )
(Q/t)= Rate of zero order drug release. Pw, Am & hm= water permeability, effective surface area & thickness of semipermeable membrane.
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Modifications
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Two compartments separated by movable partition. Osmotically active compartment absorbs water from GIT. Creates osmotic pressure. Partition moves upward & then drug releases. Ex: Nifedipine.
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Delivery orifice
Drug compartment
Movable partition
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Spansule capsule ( SK & F ) Sequal capsule (Lederle ) Extentab tablets ( Robins ) Timespan tablet ( Roche ) Dospan tablet ( Merrell Dow ) Chronotab tablet ( Schering ) Plateau capsule ( Marion ) Tempule capsule ( Armour )
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Propranolol (Inderal LA) Methyiphenidate HCl (RitalinSR) Iron (Slow-Fe) GITS-Prazosin (Minipress) Morphine sulfate (Roxanol SR) Decongestant & antihistamine (Resaid SR, Novafed SR Dristan) Pseudoephedrine HCI (Sudafed SA) Potassium (Micro-K, Slow-K, Klotrix) Antitussive combinations (Rescap, Ornade Spansules) Chlorpheniramine maleate (ChlorTrimeton) Decongestant, antihistamine and anticholinergic (Dallergy, Supres)
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Bupropion is used in the treatment of major depressive disorder. Conventional formulation has to be administered 3 times daily Initially 150 mg ER formulation was introduced for bid regimen Later on 300 mg ER formulation was introduced for once daily regimen For ER formulation provide similar Cmax and AUC values as compared to immediate release formulation at steady state.
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Single layer tablet: Drug core (water soluble drug with or without excipients) Semipermeable membrane with a drilled orifice Water imbibition by the core because of osmotic action results in drug dissolution, which is released at a controlled rate through the orifice Not suitable for water insoluble drugs. Examples: Sudafed 24 hours (Pseudoephedrine); Volmax (Salbutamol)
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This technology Controls amount, timing and location of release in body. -Formulation with predictable and reproducible drug release profile. -Controls rate of drug diffusion throughout release process, ensuring 100% release Products
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References
Novel drug delivery system , volume 50, Y.W.Chien The theory & practice of industrial pharmacy, Leon Lachman , Herbert A.Lieberman, Joseph L.Kanig,3 rd edition. The Eastern pharmacist, november 1993. Sustained release drugs, V R.Gudsoorkar & D.Rambhau page 27-32 Biopharmaceuitics & pharmacokinetics, D M.Brahmankar & Sunil B. Jaiswal. www.google.com
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