MECHANISM OF DRUG RELEASE

Drug delivery relates to the concepts of sustained release and controlled

release in terms of the pharmaceutical compound. It is released over a certain
period of time with or without electrical stimulation.

Drug Release from Controlled/Extended drug delivery systems

❖The overall release rate is affected by several physical and chemical

phenomena, e.g., a combination of

-water diffusion,

-drug dissolution,

-drug diffusion,

-polymer swelling,

-polymer dissolution, and/or

-polymer degradation

❖Diffusion plays a major role in most controlled drug delivery systems.

❖When several processes are involved, the slowest process is the dominant
rate-limiting one.

Extended Release Mechanisms

1. Diffusion Systems
 Monolithic System
 Reservoir System
2. Swelling System
3. Osmotic System
4. Biodegradable System
 Reservoir System
 Monolithic System

5. Dissolution system
  Matrix System
 Reservoir System

Diffusion Controlled Release Mechanism

❑Diffusionis the mass transport mechanism when other processes are not
involved in the control of drug release.

❑Diffusion Definition: spontaneous transfer of molecules from a region of

higher concentration to a region of lower concentration.

❑Diffusion is dominant if the impact of all other phenomena is negligible.

Diffusion controlled devices

❑The drug must diffuse through either a polymeric membrane or polymeric

or lipid matrix.

1.Reservoir devices:in which the drug is surrounded by a rate-controlling

polymer membrane (which can be non-porous, or microporous);

2.Matrix(also described as Monolithic) devices:in which the drug is

distributed throughout a continuous phase composed of polymer or lipid.
DRUG RESERVOIR RATE CONTROLLING MEMBRANE Polymeric matrix DRUG
Particle dissolved or dispersed within the polymeric matrix .

• This system is hollow containing an inner core of drug.

• The water insoluble polymeric material surrounds drug reservoir.

• The drug partitions into the membrane and exchanges with the surrounding
fluid by diffusion.

• The release drug from a reservoir device follows Fick’s first law of diffusion.
J = - D dc/dx Where, J = flux, amount/area-time D = diffusion coefficient of
drug in the polymer, area/time dc/dx = change in conc. with respect to
 polymer distance.

Swelling system
A "swelling system drug release" refers to a drug delivery method where a
polymeric matrix absorbs fluid, causing it to swell and gradually release the
embedded drug over time, controlled by the rate of swelling; essentially, the
expansion of the matrix due to water absorption acts as the primary
mechanism for drug release.
Key points about swelling system drug release
Mechanism:
When the polymer matrix comes into contact with bodily fluids, it absorbs
water, leading to an increase in volume and creating pathways for the drug
to diffuse out.
Controlled release:
By adjusting the polymer properties (cross-linking degree, hydrophilicity)
the rate of swelling can be manipulated, allowing for controlled drug release
over a desired period.
Applications:
This system is particularly useful for oral drug delivery, enabling sustained
release of drugs in the gastrointestinal tract, reducing the need for frequent
dosing.
Examples of polymers used in swelling systems:
 Hydroxyethyl cellulose (HEC): A commonly used hydrophilic polymer that
readily swells in water.
 Hydroxypropyl methylcellulose (HPMC): Another widely used cellulose
ether with adjustable swelling properties.
 Polyvinyl alcohol (PVA): A synthetic polymer that can be cross-linked to
achieve desired swelling behavior.
Important factors affecting swelling-controlled drug release:
 Polymer structure: Cross-linking density, molecular weight, and degree of
substitution
 Drug loading: Concentration of drug within the polymer matrix
 Environmental conditions: pH, temperature, and ionic strength of the
surrounding fluid.

Osmotic system
In this system, the flow of liquid into the release unit driven by a difference in
osmotic pressure between the inside and the outside of the release unit is
used as the release-controlling process.

Drug may be osmotically active or drug may be combined with osmotically

active salts like NaCl.
Osmotic delivery systems or osmotic pumps are mainly composed of a core
containing a drug and an osmogen

Biodegradable System

Degradation can take place via:

1.Bioerosion: the gradual dissolution of a polymer matrix;

2.Biodegradation: degradation of the polymer structure caused by chemical or

enzymatic processes.

Classification of polymer degradation

A.Bulk erosion, all polymer matrix is subject to chemical or enzymatic reactions,

thus erosion occurs homogeneously throughout the matrix B.Surface erosion,
polymer degradation is limited to the surface. Erosion therefore starts at the
exposed surface and works downwards, layer by layer.

E.g., Poly-lactide and poly-lactide-co- glycolide polymers

❖Polyesters, such as poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid)

(PLGA), are examples of biomaterials that are degraded by homogeneous bulk
erosion.

❖The polymers are prepared from lactide and glycolide, which are cyclic esters of
lactic and glycolic acids.
❖Polymer degradation generally takes place in four major stages:

1.Polymer hydration causes disruption of polymer structure

2.Strength loss is caused by the rupture of ester linkages in the polymers.

3.Loss of mass integrity results in initiation of absorption of polymeric fragments.

4.Finally smaller polymeric fragments are phagocytosed, or completeddissolution

into glycolic and lactic acids occurs.

Biodegradable systems release drugs through a combination of diffusion and

biodegradation. The rate of release depends on a number of factors, including
the size and morphology of the particles, the properties of the drug, and the
rate at which the polymer degrades.
Natural Biodegradable Polymers

1. Proteins:

▪albumin

▪collagen

▪gelatin

2. Polysaccharides

▪Dextran

▪hyaluronic acids

Dissolution system

In dissolution-controlled products, the drug dissolution rate is controlled by

means of slowly soluble polymers or by microencapsulation. By means of slow
dissolving polymer, coating of individual particles or granules of drug can be
accomplished in the encapsulated dissolution system (reservoir system).

Dissolution-controlled devices can be divided into:

1.Reservoir devices: drug is surrounded by a polymeric membrane which retains

the drug. After a certain period, the polymeric membrane dissolvesreleasing the
drug .

2.Matrix devices: drug is distributed throughout a polymeric matrix, which

dissolves with time, thereby releasing the drug.

Drug is encapsulated in partially soluble membrane, pores are created due to

soluble parts of coating film which permits entry of aqueous medium into core
and drug dissolution starts by diffusion of dissolved drug out of system.
Mixture of water soluble PVP and water insoluble ethyl cellulose is used for
this purpose.
Dissolution of the drug from the polymer matrix or encapsulated forms.

• The dissolution process at a steady state is described by Noyes Whitney

equation:

dc / dt = k A/V (Cs – C)

dc / dt = (D/h) A (Cs – C)

where

, dC/dt = dissolution rate

V = volume of the solution

k = dissolution rate constant

D = diffusion coefficient of drug through pores

h = thickness of the diffusion layer

A = surface area of the exposed solid

Cs = saturated solubility of the drug

C = conc. of drug in the bulk solution 42