controlled release oral drug delivery system

37
Controlled Release Oral Drug Delivery System Bhupendra Kumar Yadav M.Pharm University Institute of Pharmacy Pt.Ravishankar Shukla University Raipur-492010, Chhattishgarh, India E-mail: [email protected]

Upload: ravishankar-university-raipur

Post on 07-Jul-2015

617 views

Category:

Health & Medicine


5 download

DESCRIPTION

Controlled Release Oral Drug Delivery System Controlled drug delivery is one which delivers the drug at a predetermined rate, for locally or systemically, for a specified period of time.

TRANSCRIPT

Page 1: Controlled Release Oral Drug Delivery System

Controlled Release Oral Drug Delivery System

Bhupendra Kumar Yadav M.Pharm

University Institute of PharmacyPt.Ravishankar Shukla University Raipur-492010, Chhattishgarh, India

E-mail: [email protected]

Page 2: Controlled Release Oral Drug Delivery System

2

Contents

Overview of Digestive system Introduction Advantages Disadvantages

Mechanisms 1.Dissolution 2.Diffusion 3.Combination of Dissolution & Diffusion 4.Osmotic pressure controlled system References

Page 3: Controlled Release Oral Drug Delivery System

3

Digestive System

Page 4: Controlled Release Oral Drug Delivery System

4

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.

Page 5: Controlled Release Oral Drug Delivery System

5

Plasma concentration t ime profi le

Page 6: Controlled Release Oral Drug Delivery System

6

Challenges in Oral Drug Delivery

Development of drug delivery system Delivering a drug at therapeutically effective rate to desirable site.

Modulation of GI transit time Transportation of drug to target site.

Minimization of first pass elimination

Page 7: Controlled Release Oral Drug Delivery System

7

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.

Page 8: Controlled Release Oral Drug Delivery System

8

Disadvantages

Dose dumping.

Reduced potential for accurate dose adjustment.

Need of additional patient education.

Stability problem.

Page 9: Controlled Release Oral Drug Delivery System

9

Mechanism aspects of Oral drug delivery formulation

1.Dissolution : 1.Matrix 2.Encapsulation

2.Diffusion : 1.Matrix 2.Reservoir

3.Combination of both dissolution & diffusion.

4.Osmotic pressure controlled system

Page 10: Controlled Release Oral Drug Delivery System

10

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.

Page 11: Controlled Release Oral Drug Delivery System

11

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.

Page 12: Controlled Release Oral Drug Delivery System

12

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

Page 13: Controlled Release Oral Drug Delivery System

13

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

Page 14: Controlled Release Oral Drug Delivery System

14

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.

Page 15: Controlled Release Oral Drug Delivery System

15

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

Page 16: Controlled Release Oral Drug Delivery System

16

Matrix system

Rate controlling step:

Diffusion of dissolved drug in matrix.

Page 17: Controlled Release Oral Drug Delivery System

17

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.

Page 18: Controlled Release Oral Drug Delivery System

18

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

Page 19: Controlled Release Oral Drug Delivery System

19

Reservoir System Rate controlling

steps : Polymeric content in

coating, thickness of coating, hardness of microcapsule.

Page 20: Controlled Release Oral Drug Delivery System

20

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

Page 21: Controlled Release Oral Drug Delivery System

21

Osmotic Pressure Controlled Drug Delivery System

Definition

Procedure

Diagram

Modifications

Page 22: Controlled Release Oral Drug Delivery System

22

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 pressureIt is the hydrostatic pressure produced by a solution in a space divided by a semipermeable membrane due to difference in concentration of solutes.

Page 23: Controlled Release Oral Drug Delivery System

23

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,

Page 24: Controlled Release Oral Drug Delivery System

24

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.

Page 25: Controlled Release Oral Drug Delivery System

25

Osmotic Pressure Controlled System

Page 26: Controlled Release Oral Drug Delivery System

26

Osmotic Pressure Controlled System

Page 27: Controlled Release Oral Drug Delivery System

Modifications

- Immediate release system.- Osmotically active compartment system

Page 28: Controlled Release Oral Drug Delivery System

28

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.

Page 29: Controlled Release Oral Drug Delivery System

29

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

Page 30: Controlled Release Oral Drug Delivery System

30

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 )

Page 31: Controlled Release Oral Drug Delivery System

31

Some Examples of OCDDS 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)

Page 32: Controlled Release Oral Drug Delivery System

32

Recent Trends : Extended release formulation of Bupropion

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.

Page 33: Controlled Release Oral Drug Delivery System

33

Recent Trends : Extended release formulation of Bupropion

Page 34: Controlled Release Oral Drug Delivery System

34

Recent Trends: OROS Technology (ALZA corporation)

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)

ELEMENTARY OSMOTIC PUMP

Page 35: Controlled Release Oral Drug Delivery System

35

Recent trends: Geomatrix® (SKY Parma)

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

Products in market:Cordicant -uno®Madopar DRSULAR ER

Page 36: Controlled Release Oral Drug Delivery System

36

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

Page 37: Controlled Release Oral Drug Delivery System

37

Thank you for paying

attention…

If this presentation was useful to u, then please click like button