The document discusses drug dissolution, detailing the mechanisms and factors influencing gastrointestinal absorption of drugs administered orally. Multiple theories of dissolution, such as the diffusion layer model and Danckwert's model, are explained, along with factors affecting dissolution rates like physicochemical properties, formulation aspects, and processing conditions. Key parameters influencing drug solubility and dissolution are identified, emphasizing the complexity of drug absorption and distribution into systemic circulation.

1. DRUG DISSOLUTION
SUBMITTED TO –
Dr. D.C. Bhatt Sir
(Director & Dean)
Institute of Pharmaceutical Sciences
SUBMITTED BY-
Sidharth
Roll no.190121220005
M.Pharmacy (Pharmaceutics)
2nd Semester
DEPARTMENT OF PHARMACEUTICAL SCIENCES,
GURU JAMBHESHWAR UNIVERSITY OF SCIENCES & TECHNOLOGY, HISAR

2. CONTENTS
 Introduction
 Factors Affecting GI Absorption of a Drug
 Definition
 Mechanism of Dissolution
 Biopharmaceutics classification system for
Drugs
 Theories Of Dissolution
 Factors Affecting Dissolution Rate

3. Introduction
Majority of drugs are administered extravascularly i.e. Orally.
Such drugs can exert their pharmacological action only when they come
in systemic circulation from site of application.
For this, ABSORPTION is important step.
For a drug to be absorbed and distributed into organs & tissues, it must
pass through biological membranes.

4. FACTORS AFFECTING GI ABSORPTION OF A DRUG-

6. Definition-
• Dissolution is a process in which a solid
substance solubilizes in a given solvent i.e.
mass transfer from the solid surface to the liquid
phase.
• Rate of dissolution is the amount of drug
substance that goes in solution per unit time
under standardized conditions.

7. Fig.The rate-determining steps in absorption of drugs
Eg. of Lipophilic Drugs-Griseofulvin & Spironolactone
Eg. of Hydrophilic Drugs-Cromolyn sod. & Neomycin

8. Mechanism of Dissolution-
1) Initial mechanical lag
2)Wetting of dosage
form
3) Penetration of
dissolution
medium
4) Disintegration
5) Deaggregation
6) Dissolution
7) Occlusion of some
particles

9. Biopharmaceutics classification
system for Drugs-

10. Theories Of Dissolution-
1) Diffusion layer model/Film theory
2) Danckwert's model/Penetration or
Surface renewal theory
3) Interfacial barrier model/Double-barrier or
Limited solvation theory

11. 1. Diffusion Layer Model/Film
Theory:-
It involves 2 steps:-
a) Solution of the solid to form stagnant film
or diffusive layer which is saturated with
the drug.
b) Diffusion of the soluble solute from the
stagnant layer to the bulk of the solution;
this is r.d.s in drug dissolution.

13. •The rate of dissolution is given by Noyes and
Whitney:
dc/dt=k (Cs - Cb)
Where,
dc/dt= dissolution rate of the drug
K= dissolution rate constant
Cs= concentration of drug in stagnant layer
Cb= concentration of drug in the bulk of the
solution at time t
dc/dt=k (Cs - Cb)

14. Modified Noyes-Whitney’s Equation -
dC/dt =DAKw/o (Cs– Cb)/Vh
where,
D= diffusion coefficient of drug.
A= surface area of dissolving solid.
Kw/o= water/oil partition coefficient of drug.
V= volume of dissolution medium.
h= thickness of stagnant layer.
(Cs– Cb)= conc. gradient for diffusion of drug.

15. 2) Danckwert’s model/Penetration or
surface renewalTheory:-
• Dankwert takes into account the eddies or
packets that are present in the agitated fluid
which reach the solid-liquid interface, absorb
the solute by diffusion and carry it into the bulk
of solution.
•These packets get continuously replaced by
new ones and expose to new solid surface
each time, thus the theory is called as surface
renewal theory.

17. •The Danckwert’s model is expressed by
equation-
V dC/dt = dm/dt = A (Cs-Cb).
Where,
m = mass of solid dissolved
Gamma (γ) = rate of surface renewal
D

18. 3) Interfacial layer model
In this model it is assumed that the reaction at solid
surface is not instantaneous i.e. the reaction at solid
surface and its diffusion across the interface is slower
than diffusion across liquid film,therefore the rate of
solubility of solid in liquid film becomes the rate
limiting than the diffusion of dissolved molecules
equation :
G = Ki (Cs – Cb )
G = dissolution rate per unit area
Ki = effective interfacial transport rate
constant

19. Fig. Interfacial barrier model for drug dissolution

20. FACTORS AFFECTING DISSOLUTION
RATE:-
1. Factors related to Physicochemical
Properties of Drug
2. Factors related to Drug Product
Formulation
3. Processing Factor
4. Factors Relating Dissolution
Apparatus
5. Factors Relating DissolutionTest
Parameters

21. A) PHYSICOCHEMICAL PROPERTIES OF DRUG -
1. PARTICLE SIZE OF DRUG:-
Surface area increases with decrease in particle
size,higher dissolution rates may be achieved
through reduction of particle size.
E.g. Micronisation of non-hydrophobic drug like
griseofulvin leads to increase in dissolution rate.

22. 2. DRUG SOLUBILITY:-
Minimum aqueous solubility of 1% is required.
Eg.Poorly soluble drug : griseofulvin, spironolactone
- Anhydrous forms dissolve faster than hydrated form
because they are thermodynamically more active than
hydrates.
E.g. Ampicillin anhydrate faster dissolution rate than
trihydrate.
- Amorphous forms of drug tend to dissolve faster than
crystalline materials.
E.g. Novobiocin , Griseofulvin.
3. SOLID STATE CHARACTERISTICS:-

23. - Metastable (high activation energy) polymorphic form have
better dissolution than stable form. Eg. Methyl prednisone.
4. 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.
- E.g. sodium and potassium salts of Penicillin G, phenytoin,
barbiturates, tolbutamide etc.

24. B) FACTORS RELATEDTO DRUG PRODUCT FORMULATION-
1. BINDERS:-
-The hydrophilic binders like gelatin increase dissolution rate of
poorly wettable drug.
- Non aqueous binders such as ethyl cellulose retard the drug
dissolution.
- Phenobarbital tablet granulated with gelatin solution provide a
faster dissolution rate in human gastric juice than those prepared
using Na – carboxymethyl cellulose or polyethylene glycol 6000
as binder.
Note:- Large amount of binder increase hardness & decrease
disintegration /dissolution rate of tablet.

25. - Disintegrating agent added before & after the
granulation affects the dissolution rate.
- Studies of various disintegrating agents on
Phenobarbital tablet showed that when copagel
(low viscosity grade of Na CMC) added before
granulation decreased dissolution rate but if added
after did not had any effect on dissolution rate.
2. DISINTEGRANTS:-

26. 3. EFFECT OF LUBRICANTS:-
- Lubricants are hydrophobic in nature and prolong the tablet
disintegration time by forming water repellent coat around
individual granules.This retarding the rate of dissolution of
solid dosage forms.
- However, if an enhancing effect in dissolution of
hydrophobic granules is desired, water soluble lubricant
such as SLS or CARBOWAXES 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.
E.g Non-ionic surfactant Polysorbate 80 increase
dissolution rate of phenacetin granules.

27. Tablets with MC coating were found to exhibit lower dissolution
profiles than those coated with HPMC at 37ºC.The differences
are attributed to thermal gelation of MC at temp near 37º,
which creates a barrier to dissolution process.
5. COATING POLYMERS:-

28. C) PROCESSING FACTORS-
1. METHOD OF GRANULATION:-
-Wet granulation has been shown to improve the dissolution
rate of poorly soluble drugs by imparting hydrophilic
properties to the surface of granules.
- 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.

29. 2. COMPRESSION FORCE:-
The compression process influence density, porosity, hardness,
disintegration time & dissolution of tablet.
3. DRUG EXCIPIENT INTERACTION:-
-These interactions occur during any unit operation such as mixing,
milling, blending, drying or granulating result change in
dissolution.
- Increase in mixing time of formulation containing 97 to 99%
microcrystalline cellulose (slightly swelling disintegrant) result in
enhance dissolution rate of prednisolone.
- Polysorbate-80 used as excipient in capsules causes formation of
formaldehyde by autoxidation which causes film formation by
denaturing the inner surface of capsule.This causes decrease in
dissolution rate of capsules.

30. 4) STORAGE CONDITIONS:-
- Dissolution rate of Hydrochlorthiazide tablets
granulated with acacia exhibited decrease in
dissolution rate during 1 yr of aging at RoomTemperature.
- A similar decrease was observed in tablets stored for 14 days
at 50-80ºC or for 4 weeks at 37ºC.
-Tablets with starch gave no change in dissolution
rate either at RoomTemperature or at elevated temperature.

31. D) FACTORS RELATED TO DISSOLUTION APPARATUS
1) AGITATION:-
In order to prevent turbulence and sustain a reproducible
laminar flow, which is essential for obtaining reliable results,
agitation should be maintained at a relatively low rate.
Thus, in general relatively low agitation should be applied.
I. BASKET METHOD- 100 rpm
II. PADDLE METHOD- 50-75 rpm

32. 2. SAMPLING PROBE POSITION:-
USP states that sample should be removed at
approximately half the distance from the upper surface of
basket or paddle and surface of dissolution medium and not
closer than 1 cm to the side of the flask.
3. STIRRING ELEMENT ALIGNMENT:-
-The USP states that the axis of the stirring element must
not deviate more than 0.2 mm from the axis of the
dissolution vessel.
-Tilt in excess of 1.5◦ may increase dissolution rate from 2
to 25%.

33. E) FACTORS RELATING DISSOLUTIONTEST PARAMETERS:-
1) TEMPERATURE:-
- Drug solubility is temperature dependent, therefore
careful temperature control during dissolution process is
extremely important.
- Generally, a temperature of 37º ± 0.5 is maintained
during dissolution determination of oral dosage forms and
suppositories.
2) VIBRATION:-
The excessive vibration of dissolution apparatus increases
dissolution rates.

34. 3) VESSEL DESIGN AND CONSTRUCTION:-
Plastic vessels provide more perfect hemisphere than glass
vessels.
4) pH OF DISSOLUTION MEDIUM:-
Weak acids---dissolution rate increases with increase in pH
whereas, for weak bases---increase with decrease in pH.

35. References:
1) SubrahmanyamCVS.Text book of physical pharmaceutics.
2nd edition,Vallabh prakashan, Delhi, 2000.
2) Brahmankar DM, Sunil BJ. Biopharmaceutics and
pharmacokinetics. 3rd edition,Vallabh prakashan, Delhi, 2015.
3) Shahebaz N.G, Jigar R.Vyas, Umesh M. Upadhyay and Aiyub
A.Patel. Study of processing parameters affecting dissolution
profile of highly water soluble drug. Scholars Research
Library. 2013;5(3):211-222.