# Models of oral drug delivery

Models of oral drug delivery

Session Objectives

By the end of this session, students will be able to:

Explain different models of oral drug delivery

Comment mechanism of drug release in various oral delivery systems

Apply concepts of microencapsulation techniques in dosage form development

Different types of the controlled drug delivery system

1. Dissolution controlled release

A)     Encapsulation dissolution control

B)      Matrix dissolution control

2. Diffusion controlled release

A)     Reservoir Devices

B)      Matrix Devices

3. Diffusion & dissolution controlled system

4. Osmotically controlled release

C)      Elementary Osmotic pumps

D)     Push pull Osmotic Pumps

E)      Controlled porosity Osmotic pumps

5. Hydrodynamically balanced system

6. pH controlled delivery system

7. Ion exchange controlled delivery system

Dissolution controlled release systems

Rate of diffusion from the solid surface to the bulk solution = Rate limiting step

– Flux= (diffusion coefficient) x (concentration gradient)

J = - D (dc / dx)

OR

Flux = flow rate of material (dm / dt ) through a unit area ( A )

J = ( 1 / A ) dm / dt

If the concentration gradient is linear and thickness of the diffusion layer is h

dc / dx = ( Cb – Cs) / h

Combining the above equations:

dm/dt = - ( D A /h ) ( Cb – Cs ) = kA (Cs – Cb)

Types of dissolution models

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

Matrix dissolution controlled system

This systems are called as monoliths

The rate of drug availability is controlled by the rate of penetration of the dissolution fluid into the matrix

Factors considered are porosity ,wettability , particle size ,  hydrophobic additives

Hydrophobic matrix ex: EC ,polypropylene, polyethylene oxide

Hydrophilic matrix ex: MC ,HPMC, NaCMC, HPC

Mechanism of monolithic drug release

Controlled dissolution can be achieved by:

1.       Altering porosity of tablet

2.       Decreasing its wettability

3.       Dissolving at slower rate

4.       First order drug release

Drug release determined by dissolution rate of polymer

Examples: Dimetane extencaps, Dimetapp extentabs

Matrix Dissolution Products

 Product Active Ingredients Manufacturer Dimetapp  Extentabs Brompheniramine Robins Donnantal  Extentabs ..... Robins Quinidex  Extentabs Quinidine Robins Tenuate Dospan Diethylpropion Merrel

RESERVOIR DISSOLUTION CONTROL MODEL

1.       Slowly dissolving substance is used to coat individual particle or granule

2.       Membrane thickness plays an important role in drug release

3.       Microencapsulation : Applying a thin coating to solids or liquids, liquids can be effectively converted into solids by this method

Micro encapsulation can be of following types :

1)      Coacervation phase separation

2)      Interfacial polymerization

3)      Electrostatic method

4)      Hot melt              method

5)      Precipitation method

6)      Salting out method

7)      Solvent evaporation method

Coacervation-phase separation can be done with the:

a)      Formation of 3 immiscible phases

b)      Deposition of coating material

c)       Solidification of coating material

 Method Mechanism involved Examples Temperature change Phase separation of dissolved polymer - immiscible droplets Ethyl cellulose & cyclohexane at high temperature Salt addition Soluble inorganic salts added Gelatin- water – sodium sulphate Non solvent addition Addition of liquid insoluble in polymer solution Paracetamol & cellulose acetate Incompatible polymer addition Incompatibility of polymer in the same solvent Methylene blue –EC- polybutadiene Polymer-polymer interaction Oppositely charged polyelectrolytes --- complex  of reduced solubility Gelatin –acacia - gelatin

Electrostatic method: the drug and coating material should be in the  form of aerosols and oppositely charged ; drug and polymer are atomized to  form microcapsules and collected using the aerosol collecting method

Interfacial polymerization: dispersion of organic phase containing drug particles into aqueous phase containing monomers; where they react at liquid- liquid interface to form a capsule wall, a crosslinking agent can be added. Low melting solids or poorly soluble organic liquids

Precipitation process: the objecti.ve of this process is to precipitate or congeal a preformed polymer around the drug being encapsulated.  Eg: sodium alginate & aq. Calcium chloride solution

Hot melt technique: at a high temperature mechanical drop formation is induced with concurrent cooling, the coating for hot melt technique consist of lipids with low molecular weight. Thermally stable compound can be only  used

Salting out method: an aqueous polymer solution is prepared to which  salt is added leading to the separation of the polymer solution , high level of  the salt concentration into capsule shell

Solvent evaporation method : the drug and capsule wall forming  material are solubilized in organic volatile solvents immiscible with water , an  emulsion is formed by dispersion into aqueous solution , solid micro capsules  are formed after solvent evaporation

 Product Active Ingred Manufacturer Ornade Spansules PPA, chlorphen. SKB Contact PPA, others SKB Diamox Sequels Acetazolamide Lederle(WA) Chlor-Trimeton  Repetabs Chlorphen Schering

Summary

• Different types of controlled release systems are:  Dissolution system, Diffusion system, Dissolution & diffusion  system, Osmotic regulated system, pH regulated system, Ion  exchange controlled systems and Hydrodnynamically  balanced systems
• Types of dissolution models are controlled and pulsed delivery systems. The drug release from dissolution controlled delivery  systems are dependent upon porosity ,wettability ,particle size  & hydrophobic additives in the formulation