Modified release drugs

Question 1

What is modified release?

Answer 1

Preparation where the rate and/or place of release is different from that of conventional release forms

Question 2

Components of MR drug

Answer 2

1. Active drug
2. Release controlling agents
   - Matrix formers (hydrogenated vegetable oils, carnauba wax, microcrystalline wax)
   - Membrane formers (ethyl cellulose, acrylic copolymers, shellac)
3. Matrix or membrane modifiers
   Channelling agents such as sodium chloride, sugars, polyols, hydrophobic matrices and solubilisers for hydrophilic matrices
4. Solubiliser
   PEG’s, polyols surfactants and pH modifiers
5. Lubricants
   Magnesium stearate and glidant (talc, colloidal silicon dioxide)
6. Supplementary coating
   To extend lag time
   Further reduce drug release

Question 3

Diffusion controlled release systems

Answer 3

Transport of dissolved drugs in pores filled with gastric or intestinal fluid or in a solid phase by diffusion
a.) Matrix or monolithic systems
Diffusion occurs in pores located within the bulk of the release unit
b.) Reservoir or membrane-controlled system
Diffusion occurs in a thin-water insoluble film or membrane which surrounds the release unit

Question 4

Soluble matrix

Answer 4

Drug becomes available as the matrix dissolves or swells and dissolves
a.) True gels – cross linked polymeric structures
Alginic acid with gelatin
b.) Viscous matrices – Simple entanglement without crosslinkes
HPMC, sodium alginate

Question 5

Insoluble matrix

Answer 5

Drug becomes available as solvent enters the matrix and dissolves the particles
Lipid matrices and insoluble polymer matrices
Polyvinyl acetate, ethylcellulose

Question 6

Reservoir or membrane-controlled systems

Answer 6

Drug reservoir coated with a membrane
Aqueous medium diffuses into the system and forms a continuous phase initiating drug diffusion and release
Membrane has to become permeable in order to allow drug to diffuse out

Question 7

Dissolution controlled release systems

Answer 7

Rate of dissolution of drug in the GI fluid
Soluble drugs are an ideal candidate
In order to achieve prolonged release the tablet is formulated to release the drug in a series of consecutive pulses (pulsatile release)
Delayed release tablets can also be made using this system

Question 8

Erosion controlled release systems

Answer 8

Rate of drug release controlled by the erosion of a matrix in which the drug is dispersed
- Matrix material in which the drug is dissolved/dispersed is liberated from the surface of the tablet
- Drug gets exposed to GI fluids and mixes or dissolves in the fluid
Lipids or waxes (polymers that gel in contact with water i.e. Hydroxyethyl cellulose)

Question 9

Osmosis controlled release systems

Answer 9

Flow of liquid into the release unit driven by the difference in osmotic pressure inside and outside the release unit
Dissolution of drug occurs
Convective transport of a saturated drug solution by pumping of a solution through a single orifice or through pores in the semi-permeable membrane

Question 10

Advantages of MR formulations

Answer 10

Improved control over maintenance of plasma-drug concentration
Improved patient compliance due to reduction in number and frequency of doses
Reduction in incidence and severity of localised GI side effects
Cost savings due to better disease management

Question 11

Limitations of MR formulations

Answer 11

Variable physiological factors (pH, enzymatic activity, gastric/intestinal transit rates, food and severity of disease interfere with drug release and absorption
Drugs with low biological half-lives are not suitable for MR formulations
Transit rate of MI products along GIT limits maximum period for which a therapeutic response can be maintained
Unsafe overdosage
Cost is more per unit dose