This topic involves full description of drug product performance

1. DRUG PRODUCT
PERFORMANCE
JOEL JOSHUA.J
Department of Pharmaceutics
Nandha College of Pharmacy

7. IN-VITRO
 In-vitro test for the active ingredient to release from
the dosage form is based on:-
Disintegration of product
Dissolution of active ingredient

8. IN VITRO DISSOLUTION OF
DRUG PRODUCT IS BASED ON
FACTORS LIKE:-
1. Drug substance related factors
2. Factors related to formulation
3. Factors related to manufacturing process
4. Factors related to dissolution test apparatus

9. DRUG SUBSTANCE RELATED FACTORS
Dissolution refers to the process of solubilization of the drug into the
dissolution medium.
Dissolution process is controlled by the affinity between the solid and
the dissolution medium.
Noyes and Whitney in 1897 proposed a fundamental equation for
dissolution:-
dm/dt = K X (Cs - Ct)
dm/dt = rate of dissolution
k = proportionality constant or dissolution constant
Cs = concentration at saturation
Ct = concentration at time t
Factors are:-
Drug solubility
Polymorphism
Salt factor
Surface area and particle size

10. DRUG SOLUBILITY
The drug substance solubility of a drug is related to the
dissolution rate of drug.
Higher dissolution rates are given by drugs which have high
solubility.
The solubility of compounds containing “ionizable groups” is a
function of the pH of the dissolution media and pKa of the
compound.
Solubility of a drug is determined using an equilibrium solubility
method and involves suspending an excess amount of solid drug in
selected aqueous medium.

11. POLYMORPHISM OF DRUG
When a drug substance :-
existing in two or more crystalline phases that have different
arrangement/conformation of the molecule in the crystal lattice
having different hydrate forms
Having amorphous phases which do not possess a distinguishable
crystal lattice
Dissolution rates of drugs having various polymorphic form are
effected due to different lattice energies of the polymorphs which
have different solubility.
Crystalline form has less solubility than the amorphous form due to
fixed and compact lattice structure
Example :- Two polymorphic forms of Chloramphenicol palmitate
exist which are A and B, form B is better orally absorbed than form A
due to greater solubility.

12. Unionizable molecules are less water soluble as
compared to the organic salts which offers a criterion for
improving the rate of dissolution.
So,during the development of drug salts of
weak bases and weak acids are chosen .
Example :- The non-steroidal anti-inflammatory drug
‘Naproxen’ was originally marketed as a free acid for the
treatment of rheumatoid or osteo- arthritis.

13. FACTORS RELATED TO FORMULATION
Drug product dissolution is greatly affected by the excepients which are used in
the
formulation.
For dosage forms which are for immediate release, those excepients are are
used which help in enhancing the dissolution rate.
Disintegrants like sodium starch glycolate and croscarmellose facilitate the
deaggregation and promote the breakup of tablets into granules.
The disintegrants effect is to provide an increased surface area of the drug
particle and hence
promoting dissolution.
Surfactants can also be included to increase the dissolution rates e.g. sodium
lauryl sulphate.

14.  Several manufacturing variables can affect the drug product
dissolution characteristics so here, manufacturing strategies may
be employed to enhance dissolution rates.
 For example, spray drying of the active ingredient with excipients
such as polyvinyl pyrrolidine (PVP) can be used to generate
stabilized amorphous dispersions, which have greatly accelerated
dissolution rates.
 Improved wetting of hydrophobic drug surfaces and enhanced
dissolution rates are sometimes achieved by employing wet
granulation vs. dry granulation processes, during product
manufacture.

15. DISSOLUTION TEST FACTORS
The dissolution test parameters such as:-
Apparatus type
Rotation speed
Dissolution medium pH
Volume

16. IN VITRO DRUG
PRODUCT
PERFORMANCE
EVALUATION
Disintegration test :-
It is a qualitative test.
An official disintegration apparatus, the USP basket rack assembly, is used to
perform the test, which is generally applicable only to immediate-release products.
When product dissolution is rapid (defined by ICH as dissolution NLT 80% in 15min
at pH 1.2, 4.0, and 6.8) and the dosage form contains drugs that are highly soluble
throughout the physiological range, disintegration testing may be meaningful.
The ICH Guidance considers a drug substance to be highly soluble when the
highest dose strength is soluble in 250mL or less of aqueous media over the pH
range of 1.2-6.8.

17. DISINTEGRATION APPARATUS

18. The test quantitatively measures the amount of active drug that dissolves from
the dosage form in a liquid dissolution medium using standard dissolution
apparatus and procedures.
Apparatus
Apparatus 1 (basket) and 2 (paddle), the apparatus most commonly used for
studying the dissolution of solid oral dosage form. The basket at 100 rpm is
commonly used for testing capsules, and the paddle at 50 rpm for tablets.
Media
The selection of a dissolution test medium is based on the physico-chemical
properties of the drug substance and characteristics of the dosage form.
Media with pH ranging from 1.2 (gastric pH) to 6.8(intestinal pH) are generally
preferred.
The most common media used in dissolution testing are water, 0.1N
hydrochloric acid, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer.
The temperature of the dissolution bath is usually maintained at 37 0.5C to
reflect human body
temperature

19. .
Tolerance
The dissolution test acceptance criterion, or tolerance, is specified in terms
of the quantity (‘‘Q’’)
that is dissolved within a specified time interval.
for most oral dosage forms, 75% or 80% (‘‘Q’’) of the labelled amount of
the active drug ingredient is specified to be dissolved within a set time
duration (test times between 15 and 60min are most common).

20. DISSOLUTION TESTER

21. APPLICATIONS OF IN VITRO
DISSOLUTION
Product Development
In vitro dissolution is an important and useful tool during
the development of a dosage form. In vitro dissolution often
aids in guiding the selection of prototype formulations and
for determining optimum levels of ingredients to achieve drug
release profiles.
Product Stability
In vitro dissolution is also used to assess drug product
quality with respect to stability and shelf life.
As products age, physicochemical changes to the dosage
form may alter the dissolution characteristics of the drug
product over time.
For example, as the moisture level increases or decreases over
time, this can result in altered tablet hardness and subsequent
possible changes in dissolution characteristics.

22. Thank You