EXPERIMENT NO: 07
AIM : TO PERFORM IN-VITRO DISSOLUTION PROFILE OF CONTROLLED
RELEASE AND SUSTAINED RELEASE MARKETED FORMULATION.
THEORY :
Dissolution rate may be defined as amount of drug substance that goes in the solution per unit time
under standard conditions of liquid/solid interface, temperature and solvent composition.
IMPORTANCE OF DISSOLUTION:-
Oral dosage forms remain one of the most flexible and effective treatments available to patients.
Dissolution testing is a requirement for all solid oral dosage forms and is used throughout the
development life-cycle for product release and stability testing.
It is a pivotal analytical test used for detecting physical changes in an active pharmaceutical
ingredient and formulated product. At the early stages of the drug development process, invitro
dissolution testing underpins the optimisation of drug-release from a given formulation.
The effectiveness of an oral dosage form depends upon the intrinsic ability of the drug to dissolve in
the fluids of the gastrointestinal tract prior to being absorbed into the circulation. Therefore, the rate
of dissolution of the tablet or capsule is pivotal to this process.
One of the key issues encountered within pharmaceutical development is the need to optimize the
level of drug available to the body in order to have its desired therapeutic effect. • Incorrect
optimization of this outside the therapeutic window could potentially lead to insufficient
bioavailability (and hence lack of efficacy) or conversely, too high a bioavailability, producing
unwanted adverse toxic effects to the patient.
In order to assist with dosage form optimization, dissolution testing is a standardized method for
measuring the rate of drug release from a given dosage form.
Divided into:
A) Physicochemical Properties of Drug
B) Drug Product Formulation Factors
C) Processing Factor
A) Physicochemical properties of drug:
1) Drug solubility:
Solubility of drug plays a prime role in controlling its dissolution from dosage form. Aqueous
solubility of drug is a major factor that determines its dissolution rate.
Minimum aqueous solubility of 1% is required to avoid potential solubility limited absorption
problem
2) Salt formation:
It is one of the common approaches used to increase drug solubility and dissolution rate.
It has always been assumed that sodium salts dissolve faster than their corresponding insoluble
acids. I.e. Sodium and potassium salts of Penicillin G, sulfa drugs, phenytoin, barbiturates etc
3) Particle size:
There is a direct relationship between surface area of drug and its dissolution rate.
Since, surface area increases with decrease in particle size, higher dissolution rates may be
achieved through reduction of particle size
4) Surface area:
Surface area is crucial for powder-based formulations.
It is a physical value that can be used to determine the properties of a material and has a crucial
role for characterization of pharmaceutical powders.
It has a particular importance for adsorption, heterogeneous catalysis, and reactions on
surfaces.
5) Stability:
The term drug stability refers to the extent to which a drug substance or product retains, within
specified limits and throughout its period of storage and use, the same properties and
characteristics that it possessed at the time of its manufacture.
B) Drug product formulation factors:-
1) Diluents:
Diluent in capsule & tablet influence the dissolution rate of drug dissolution rate is not only
affected by nature of the diluent but also affected by excipient dilution (drug/excipient ratio).
i.e. quinolone comp. dissolution rate increases as the excipient /drug ratio increases from 3:1 to
7:1 to 11:1.
1) Disintegrates:
Disintegrating agents added before & after the granulation affect the dissolution rate. •
Microcrystalline cellulose is a very good disintegrating agent but at high compression force, it
may retard drug dissolution.
Starch is not only an excellent diluent but also superior disintegrate due to its hydrophobicity
and swelling property.
2) Binders and granulating agents:
The hydrophilic binder increases dissolution rate of poorly wet table drug.
Large amt. of binder increases hardness & decrease disintegration /dissolution rate of tablet.
Non aqueous binders such as ethyl cellulose also retard the drug dissolution
3) Lubricants:
Lubricants are hydrophobic in nature (metallic stearates) and prolong tablet disintegration time
by forming water repellent coat around individual granules. This retarding effect is most imp
factor in influencing rate of dissolution of solid dosage forms.
Both amount and method of addition affect the property. It should be added in small amount
(1% or less) and should be tumbled or mixed gently for only very short time.
Prolonged mixing the dissolution time. If an enhancing effect in dissolution of hydrophobic
granules is desired, water-soluble lubricant such as SLS or carbowax may be used
4) Surfactants:
They enhance the dissolution rate of poorly soluble drug. This is due to lowering of interfacial
tension, increasing effective surface area, which in turn results in faster dissolution rate.
C) Processing factors:
1) Method of granulation:
Granulation process in general enhances dissolution rate of poorly soluble drug. Wet
granulation is traditionally considered superior.
A newer technology called as APOC “Agglomerative Phase of Comminution” was found to
produce mechanically stronger tablets with higher dissolution rates than those made by wet
granulation. A possible mechanism is increased internal surface area of granules produced by
APOC method
2) Compression force:
The compression process influence density, porosity, hardness, disintegration time &
dissolution of tablet.
First condition, higher compression force increase the density & hardness of tablet, decrease
porosity & hence penetrability of solvent into the tablet retard the wettability by forming a
firmer & more effective sealing layer by the lubricant and in many case tighter bonding
between the particle so decrease dissolution rate of tablet.
Second condition, higher compression force cause deformation, crushing or fracture of drug
particles into smaller ones or convert spherical granules into disc shaped particles with a large
increase in the effective surface area so increase in dissolution rate.
In short dissolution decrease at lower pressure (better bonding), then increase at higher pressure
(crushing effect) and decrease again with further increase in pressure because of extra rebounding and
formation of denser tablets with poorer dissolution characteristics.
