1. Dissolution Considerations for
Novel Immediate Release
Formulations
Presented by
Syed anees ahmEd
B. Pharm.
Rameshwaram Institute of Technology
And Management, Lucknow

2. INTRODUCTION
Novel Immediate Release Dosage Forms
Subjected to Routine Tests
Content Uniformity
Weight
Hardness
Friability
Disintegration
THE MOST OFTEN TEST ASSOCIATED WITH
ASSESSMENT OF IN VIVO PERFORMANCE IS
DISSOLUTION TEST

3. DISSOLUTION TEST
Integral component of new drugs applications to
regulatory bodies worldwide.
Classic vs. modern use of dissolution testing.
"Classic" use of dissolution tests:
Quality Control.
"Modern" use of dissolution tests:
to simulate the in vivo release behavior of
the dosage form with a view to in vitro-in vivo
correlation.

4. DECISION TREE FOR DISSOLUTION
TEST DESIGN
1. Classify the compound according to BCS.
2. Choose an appropriate medium.
Class 1, 3: use the most simple medium.
Addition of surfactants is unnecessary.
Class 2, 4: biorelevant media warranted.
SGFsp + surfactant, FaSSIF ( fasted state ).
Ensure , milk, FeSSIF ( fed state ).
SGFsp / SIFsp + suitable surfactant.

5. 3. Choose an appropriate medium volume.
Volumes for the fasted state will be lower than
volumes for the fed state.
4. Choose an appropriate test duration.
Class 1, 3: short test (up to 30 min).
Class 2, 4: test duration depends on:
- region of gut.
- fasted or fed state.
5. Apparatus: USP II for IR products mainly used.
USP I .
6. RPM: 50 or 75 rpm is usually suitable.

6. WHICH FACTORS CAN LIMIT
BIOAVAILABILITY AFTER ORAL
ADMINISTRATION?
Factors can determine the rate and extent of drug
absorption following oral administration.
1. Slow release of the drug from the dosage form.
2. Instability of the drug in the GI tract.
3. Poor permeability of the GI mucosa to the drug.
4. First-pass metabolism of the drug in the gut wall
or liver.

7. Biopharmaceutics Classification Scheme can be used
as a guide to determine whether an IVIVC can be
expected for IR product.
Table 1 The Biopharmaceutics Classification Scheme(BCS)
Class 1 Class 2
High solubility Low solubility
Good permeability Good permeability
e.g. Acetaminophen and e.g. Antifungals, Steroids,
Meteprolol NSAIDs, CV agents
and Antidiabetics
Class 3 Class 4
High solubility Low solubility
Poor permeability Poor permeability
e.g. Antiviral acyclovir,
Aminoglycoside neomycin

8. SELECTION OF DISSOLUTION
TEST MEDIA BASED ON THE BCS
A. Class 1 Substances
dose (mg)
D/S =
aq. Solubility (mg/mL)
- It yields the volume of liquid required to dissolve the
entire dose of the drug.
- The ratio exceeds the actual volume of GI fluids 
dissolution + absorption will not be complete.
- The FDA uses a D/S of 250 mL. for compounds with
good solubility.
- D/S exceeds 250 mL.  dissolution will be limiting
factor.

9. The release of drug is not limiting factor to absorption.
It limited by non dosage-form-related factors, such as
gastric emptying.
U.S. ( FDA )  recommends in a simple medium  85%
or more of the drug to be released within 30 min. for IR
dosage form of class 1 drugs.
SGF without enzyme  suitable of many IR dosage form
of class 1 drugs.
For some capsules SGF + Enzyme ( pepsin )  ensure
dissolution of the shell.
SIF without enzyme  suitable for weak acid.
FaSSIF and FeSSIF are unnecessary for dissolution of
class 1 drugs.

10. 120
100
80
% Release
60
40 FaSSIF
FeSSIF
20
0
0 10 20 30 40 50 60
Time ( min )
Fig.1 Dissolution of acetaminophen ( Panadol)
tablets in FaSSIF, and FeSSIF at 100 rpm
in a paddle apparatus.

11. B. Class 2 Substances
Compounds can be defined as being poorly soluble when
their dissolution rate is the limiting factor to their oral
bioavailability.
Suitable, biorelevant media :
1. SGFsp + Surfactant
SGFsp + Surfactant  suitable for weak bases.
e.g. of class 2 bases Ketoconazole and Dipyridamole.
In the fasted state, the absorption of both compounds is
highly dependent on gastric pH. Hypochlorhydria as a
result of cotherapy with gastric acid blockers is
associated with very poor absorption.
The presence of surfactant in the gastric fluids may play
a role in the wetting and solubilization of poorly soluble
acids in the stomach.

12. Table 2 Sample Composition for SGFsp
with Surfactant.
HCl 0.01 – 0.05 M
Triton X–100 0.01%
NaCl 0.2%
Water qs 1L

13. The influence of the surfactant Triton X- 100 on
the release rate of several albendazole products
in SGFsp.
100 100
80 80
% release
% release
60 60
40 40
Zentel Zentel
Alben Alben
20 Albendazol MK Albendazol MK
Zirkon 20 Zirkon
0 0
0 20 40 60 80 100 120
0 20 40 60 80 100 120
(a) Time ( min) (b) Time ( min)
Fig.2 Dissolution profiles of various albendazole products in acidic media (SSF sp ): upper
panel without and lower panel with 0.1% Triton X-100

14. 2. Ensure and Milk as Dissolution
Media
Mechanisms by which Ensure and milk can
improve drug solubility include solubilization of
the drug in the fatty part of the fluid.
Disadvantage:
Difficulties in filtering and separating the drug
from the medium make these media unsuitable
for routine quality assurance testing.

15. 3. FaSSIF and FeSSIF
Table 3 and 4 Show the compositions of these media,
FaSSIF and FeSSIF.
Table 3 Composition of FaSSIF.
KH2PO4 3.9 g
Na taurocholate 3 mM
Lecithin 0.75 mM
KCl 7.7 g
NaOH qs pH 6.5
Distilled water qs 1L
Table 4 Composition of FeSSIF
Acetic acid 8.65 g
Na taurocholate 15 mM
Lecithin 3.75 mM
KCl 15.2 g
NaOH qs pH 5
Distilled water qs 1L

16. These two media are useful for:
1. Forecasting the in vivo dissolution of poorly soluble
drugs.
2. Assessing potential for food effects on in vivo
dissolution.
The dissolution rate of a poorly soluble drug is better in
FaSSIF & FeSSIF than simple aqueous buffers because of
the increased wetting of the drug surface and micellar
solubilization of the drug by the bile components.
e.g. Griseofulvin, Digoxin, Diazepam, Cyclosporine,
Pentazocine and Danazol.

17. Dissolution Behavior of Various Class 2
Substances in the Different Media
Ketoconazole
120
180
80
% release
60
40
SGFsp
FaSSIF
20 FeSSIF
0
0 20 40 60 80 100 120
Time (min)
Fig. 3 Dissolution profiles of ketocanazole in
various media.
Dissolution is quickest under SGFsp, No dissolution in FaSSIF,
Important site of dissolution in FeSSIF.

18. Mefenamic acid
40
FeSSIF
30 FaSSIF
SIF
% Release
20
10
0
0 10 20 30 40 50 60
Time ( min )
Fig. 4 Dissolution profiles of mefenamic acid in
various media.
Dissolution rate in FaSSIF & FeSSIF were similar,
and agreed with the lack of influence of food on the
absorption.

19. Troglitazone
80
70
60
50 Water
% release
FaSSIF
40 FeSSIF
30
20
10
0
0 20 40 60 80 100
Time ( min )
Fig. 5 Dissolution profiles of troglitazone
in various media.
Dissolution enhanced in FeSSIF compared with
FaSSIF .

20. Use of synthetic Surfactants in
Dissolution Media
For routine quality assurance, we use synthetic
surfactant system instead of the bile components,
because:
1. Their purity.
2. Time and effort required.
e.g. SLS, Tweens, or other.
The role here depend on the type and concentration.

21. 4. Hydroalcoholic Mixtures as Dissolution
Media
Popular for poorly soluble drugs.
There advantage over the use of surfactants:
1. They don't tend to foam.
2. A wide range of pH values can be used without
affecting the surface tension properties of the
medium.
3. The solubility of some drugs is more influenced by
alcohol than by surfactant.

22. C. Dissolution Tests for Class 3
Substances
Class 3 substances fail to achieve complete
bioavailability because of their poor membrane
permeability.
Simple aqueous can be used for quality assurance
dissolution testing of IR products.
The membrane permeability is a limiting factor to
the absorption.

23. D. Dissolution Tests for Class 4
Substances
Because of poor solubility with poor
permeability they don't approach complete
bioavailability.
Chlorothiazide is an example of a borderline
case between class 3 and 4 behavior.
SGFsp and SIFsp + surfactant is used to assure
that complete release of the drug is possible.

24. DURATION OF DISSOLUTION
TEST
Drug best absorbed from Test duration of up to 4 h.
the small intestine in the
fasted state.
Drug best absorbed from Test duration of up to 6 h.
the small intestine in the
fed state.
Compound is to be Tests as long as 8 – 10 h.
absorbed well from the
colon.

25. DISSOLUTION EQUIPMENT
Apparatus
USP I (basket) and USP II (paddle) are the apparatuses
most often used for IR dosage forms.
Selection of Agitation Rate
The most often used apparatus for IR dosage forms
is USP II.
Rotation speed is too low  low rates of dissolution.
Rate of rotation is too fast  no discriminate
between acceptable and not acceptable batches.
Rotational speed 50 – 100 rpm  paddle method.
Rotational speed of up to 150 rpm  basket method.

26. REFERENCES
Galia E. et al. Evaluation of various dissolution media
for predicting in vivo performance of class I and II
drugs. Pharm Res. (1998) 15:698-705.
United states pharmacopeia 24 and National
formulary 19. Rockville, MD:United states
Pharmacopeial convention,1999.
Nicolaides E. et al. Forcasting the in vivo
performance of four low solubility drugs from their in
vitro dissolution data. Pharm Res. (1999 ) 16:1877-
1883.
Young MA. et al. improvement in the gastrointestinal
absorption of troglitazone when taken with or shortly
after, food. Br J Clin pharmacol( 1998 ) 45: 31-35.

27. Dressman JB. et al. Dissolution testing as a
prognostic tool for drug absorption : immediate
release dosage forms. Pharam Res. ( 1998 ) 15:11-
22.
Lindenberg M. et al. Classification of orally
administrated drugs on the World Health
Organization Model list of Essential Medicines
according to the biopharmaceutics classification
system. Eur. J. Pharm. Biopharm. ( 2004) 58: 265-
278.
Dressman J.B. et al. Dissolution testing as a
prognostic tool for oral drug absorption : Immediate
Release Dosage form. Pharmaceuticals Res. (1998)
15: 11-21.
Rinaki E. et al. Quantitative biopharmaceutics
classification system : The central role of
Dose/Solubility ratio: Pharm. Res. ( 2003) 20:1917-
1923.

28. Thank You