controlled dds asif ppt

Design and fabrication of oral Controlled Drug Delivery System : 

Design and fabrication of oral Controlled Drug Delivery System Md.Asif iqbal M pharm 2nd sem (pharmaceutics)

Concept : 

2 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.

Plasma concentration time profile : 

3 Plasma concentration time profile

Advantages : 

4 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.

Disadvantages : 

5 Disadvantages Dose dumping. Reduced potential for accurate dose adjustment. Need of additional patient education. Stability problem.

Design and fabrication of Oral controlled drug delivery system : 

6 Design and fabrication of Oral controlled drug delivery system 1.Dissolution : 1.Matrix 2.Encapsulation 2.Diffusion : 1.Matrix 2.Reservoir 3.Combination of both dissolution & diffusion. 4.Osmotic pressure controlled system 5.Ion exchange resins 6.Altered density formulation 7.PH independent formulations

Dissolution Definition: : 

7 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.

Dissolution-Controlled Systems : 

Dissolution-Controlled Systems Alternating layers of rate-controlling coats Group of beads with different coatings (Spansule, SmithKline Beecham) dC/dt = kd*A(Cs-C) = D/h*A(Cs-C) dC/dt=dissolution rate, kd=dissolution rate const D=diffusion coefficient, Cs=saturation solubility C=concentration of solute in bulk solution 8

Types of Dissolution Controlled Systems : 

Types of Dissolution Controlled Systems Two types of dissolution- controlled, pulsed delivery systems A: Single bead-type device with alternating drug and rate controlling layer B: Beads containing drug with differing thickness of dissolving coats 9

Bioerodible and Combination Diffusion and Dissolution System : 

Bioerodible and Combination Diffusion and Dissolution System Strictly speaking, therapeutic systems will never be dependent on dissolution only or diffusion only. Bioerodibile devices, however, constitute a group of systems for which mathematical descriptions of release is complex. The complexity of the system arises from the fact that, as the polymer dissolves, the diffusion path length for the drug may change. this usually results in a moving-boundary diffusion system. Zero-order release can occur only if surface erosion occurs and surface area does not change with time. The inherent advantage of such a system is that the bioerodible property of the matrix does not result in a ghost matrix. 10

Slide 11: 

Representation of a Bioerodible Matrix System Drug is dispersed in the matrix before release at time = 0. At time = t, partial release by drug diffusion or matrix erosion has occurred 11

Characteristics of Bioerodible Matrix Systems : 

Characteristics of Bioerodible Matrix Systems Advantages all the advantages of matrix dissolution system removal from implant sites is not necessary Disadvantages difficult to control kinetics owing to multiple processes of release potential toxicity of degraded polymer 12

Bioerodible and Biodegradable Controlled Release Polymers : 

Bioerodible and Biodegradable Controlled Release Polymers These polymers are designed to degrade within the body Polylactides (PLA) Polyglycolides (PGA) Polylactide-co-glycolides (PLGA) Polyanhydrides Polyorthoesters 13

Degradation of Biodegradable Polymers : 

Degradation of Biodegradable Polymers These materials degrade within the body as a result of natural biological processes, eliminating the need to remove a drug delivery system after release of the active agent has been completed Bulk hydrolysis - the polymer degrades in a fairly uniform manner throughout the matrix Surface Eroding - degradation occurs only at the surface of the polymer, resulting in a release rate that is proportional to the surface area of the drug delivery system 14

Biodegradable Polymers : 

Biodegradable Polymers Drug delivery from (a) bulk-eroding and (b) surface-eroding biodegradable systems. 15

Noyes Whitney Equation : 

16 Noyes Whitney Equation dc/dt = kD.A (Cs – C ) dc/dt = D/h A. (Cs – C) dc/dt = Dissolution rate. k= Dissolution rate constant (1st order). D = Diffusion coefficient/diffusivity Cs = Saturation/ maximum drug solubility. C =Con. Of drug in bulk solution. Cs-C=concentration gradient. h =Thickness of diffusion layer.

Matrix Type : 

17 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. Soluble drug Slowly dissolving matrix

Matrix Dissolution Products : 

Matrix Dissolution Products 18

Encapsulation : 

19 Encapsulation Called as Coating dissolution controlled system. Dissolution rate of coat depends upon stability & thickness of coating. Masks colour,odour,taste,minimising GI irritation. One of the microencapsulation method is used. Examples: Ornade spansules, Chlortrimeton Repetabs Soluble drug Slowly dissolving or erodible coat

Encapsulated Dissolution Products : 

Encapsulated Dissolution Products 20

Diffusion : 

21 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.

Matrix Diffusion Types : 

22 Matrix Diffusion Types 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. Examples: Glucotrol XL, Procardia XL

Matrix system : 

23 Matrix system Rate controlling step: Diffusion of dissolved drug in matrix.

Matrix Diffusional Products : 

Matrix Diffusional Products 24

Higuchi Equation : 

25 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.

Reservoir System : 

26 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

Reservoir diffusion System : 

27 Reservoir diffusion System Rate controlling steps : Polymeric content in coating, thickness of coating, hardness of microcapsule.

Reservoir Diffusional Products : 

Reservoir Diffusional Products 28

Dissolution & Diffusion Controlled Release system : 

29 Dissolution & Diffusion Controlled Release system Drug encased in a partially soluble membrane. Pores are created due to dissolution of parts of membrane. It permits entry of aqueous medium into core & drug dissolution. Diffusion of dissolved drug out of system. Ex- Ethyl cellulose & PVP mixture dissolves in water & create pores of insoluble ethyl cellulose membrane. Insoluble membrane Pore created by dissolution of soluble fraction of membrane Entry of dissolution fluid Drug diffusion

Osmotic pressure controlled DDS : 

30 Osmosis - Movement of solvent from lower to higher concentration. - The passage of solvent into a solution through semipermeable membrane. Semipermeable Membrane Molecules are permitted only to one component (Water). 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. Osmotic pressure controlled DDS

Osmotic Pressure Controlled System : 

31 Osmotic Pressure Controlled System 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,

Equation : 

32 Equation (Q/t) z = Pw Am/ hm (πs-πe ) (Q/t)= Rate of zero order drug release. Pw, Am & hm= water permeability, effective surface area & thickness of semipermeable membrane. πs= osmotic pressure of saturated solution of osmotically active drug or salt in system. πe = osmotic pressure of GI fluid.

Osmotic Pressure Controlled System : 

33 Osmotic Pressure Controlled System

Osmotic Pressure Controlled System : 

34 Osmotic Pressure Controlled System

Modifications : 

Modifications - Immediate release system. - Osmotically active compartment system

Immediate Release System : 

36 Immediate Release System Activation of system is done. Dividing a dose into two parts. One third immediate release. Two third controlled release. Encapsulated into semipermeable membrane. e.g. : Phenyl propanolamine.

Osmotically active system : 

37 Osmotically active system Two compartments separated by movable partition. Osmotically active compartment absorbs water from GIT. Creates osmotic pressure. Partition moves upward & then drug releases. Ex: Nifedipine. Movable partition Delivery orifice Osmotically active compartment Drug compartment

Some Popular Brand names used for OCDDS : 

38 Some Popular Brand names used for OCDDS 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 )

Ion exchange resins : 

Ion exchange resins It is based on the formation of drug resin complex formed when a ionic solution is kept in contact with ionic resins. The drug from these complex gets exchanged in gastrointestinal tract and released with excess of Na+ and Cl- present in gastrointestinal tract. Resin + - Drug - + Cl- goes to resin + Cl- + Drug- Where x- is cl- conversely Resin - - drug+ + Na +goes resin – Na+ + Drug These systems generally utilize resin compounds of water insoluble cross – linked polymer. They contain salt – forming functional group in repeating positions on the polymer chain. The rate of drug diffusion out of the resin is sustained by the area of diffusion, diffusional path length and rigidity of the resin which is function of the amount of cross linking agent used to prepare resins 39

PH -independent formulations : 

PH -independent formulations Drugs administered oraly encountered pH ranging from 7 in mouth,1 to 4 in stomach, and 5 to 7 in small intestine.since most of the drugs are eighter weak acids or weak bases,their release from sustained formulations is PH dependent. However buffer can be added to the formulation to help maintain a constant PH there by rendering pH-independent release. To this end,salts of amino acids,citric acid,phthalic acid,phosphoric acid or tartrate acid are commonly used because of their physiological acceptibility. e.g. propoxyphene in a buffered sustained release formulation, which significantly increase reproducibility 40

Altered density formulations : 

Altered density formulations 1.High desity approch: the density of the pellets must exceed that of normal stomach content(1.04g/cm3) and should be atleast 1.4 In preparing such formulations,drug can be coated on a heavy core or mixed with heavy inert materials such as barium sulfate,titanium dioxide ,iron oxide. 2.low density approch : Globular shells which have an apparen density lower than that of gastric fluid can be used as a carrier of drug for sustained release purpose.polysterol,poprice,and even popcorn are all good condidates as carriers. The surface of these empty shells is undercoated with sugar or with a polymeric material such as methacrylic polymer and cellulose acetate pthalate.the undercoated shell is then coated by a mixture of drug with polymers such as ethylcellulose and hydroxypropylcellulose.Final product floats on GIT fluid. 41

Conclusion : 

Conclusion By and large, these are based on the principles diffusion, dissolution, or ion exchange and, only recently, on the principle of osmosis. Regardless of the mechanism of sustained release, however, more and more of these systems are becoming polymer based. There are also those which are based on the bioadhesion principle whose goal is to promote the retention of a delivery system, hence drug release, at a specific region in the GI tract 42

References : 

43 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.

Continue…………… : 

Continue…………… Li. V.H., "Influence of drug properties and routes of drug administration on the design of sustained and controlled release systems" Chapter 1 in "Controlled drug delivery : fundamentals and applications" edited by Robinson J.R., VincentLee,2ndedition,Marcel Dekker Inc., Volume 29, 1978: 5-36pp Hui ho-wah, "Design and fabrication of oral controlled release drug delivery systems“ chapter 9 in "Controlled drug delivery; fundamentals and applications", edited by Robinson J.R., Vincent Lee, 2nd edition, Marcel Dekker Inc., Volume 29, 1978: 391-420pp. 44

Questions? : 

Questions? 45

Thank You : 

Thank You 46