Is the processes by which solid substance enters the solvent phase to yield a solution i.e. mass transfer from solid surface to liquid phase.

1. Mr. Sagar Kishor Savale
[Department of Pharmaceutics]
avengersagar16@gmail.com
2015-2016
6/4/2016 1sagar kishor savale

2. 1 Definition .
2 Importance Of Dissolution Study.
3 Selection Of Dissolution Media.
4 Operating parameter.
5 Types of dissolution media.
6 Conclusion.
7 Reference.
6/4/2016 2sagar kishor savale

3. • Is the processes by which solid substance enters the
solvent phase to yield a solution i.e. mass transfer
from solid surface to liquid phase.
6/4/2016 3sagar kishor savale

4.  Dissolution testing is mainly used to confirm product
quality and batch to batch consistency.
 Find problems in Bioavailability.
 In R &D department ,comparing in vitro dissolution
data with in vivo bioavailability.
6/4/2016 4sagar kishor savale

5. • The selection of an appropriate dissolution medium is a
fundamental stage of the dissolution test.
• It is more important that the test closely simulate the environment
in the GI tract than necessarily produce sink condition.
 SINK CONDITION:
The dissolution rate may be given by Novey-Whitney equation.
Where, S : surface area
t: time
Cs-Ct: concentration gradient between the concentration of
solute in the stagnant layer
6/4/2016 5sagar kishor savale

6. • dW/dt = K
• This represents that the dissolution rate is constant under sink conditions.
We have to maintain sink condition in in-vitro. This is can be achieved by,
 Bathing the dissolving solid in fresh solvent from time to
time.
 Increasing the volume of dissolution fluid.
 Adding a water miscible solvent such as alcohol to the
dissolution medium.
 By adding selected adsorbent to remove the dissolved drug.
6/4/2016 6sagar kishor savale

7. Type of dosage form Recommended Apparatus
Solid oral dosage forms Basket, paddle, reciprocating, cylinder, or flow-through cell
(conventional)
Oral suspensions Paddle
Oral disintegrating tablets Paddle
Chewable tablets Basket, paddle, or reciprocating, cylinder with glass beads
Transdermal—patches Paddle over disk
Topical —semisolids Franz cell diffusion system
Suppositories Paddle, modified basket, or dual, chamber flow-through cell
Chewing gum Special apparatus [European Pharmacopoeia (PhEur)]
Powders and granules Flow-through cell (powder/granule sample cell)
Microparticulate formulations Modified flow-through cell
Implants Modified flow-through cell6/4/2016 7

8. 1. VOLUME:
• The recommended volume of dissolution medium is 900ml when using
the basket or paddle apparatus.
• The volume can be raised to between 2 and 4 L, depending on the
concentration and sink conditions of the drug solution.
2. TEMPERATURE:
• The standard temperature for the dissolution medium is 37±0.5°C for oral
dosage forms.
• Slightly increased temperatures such as 38±0.5°C have been
recommended for dosages forms such as suppositories.
• Lower temperatures such as 32±0.5°C are utilized for topical dosage forms
such as transdermal patches and topical ointments.
6/4/2016 8sagar kishor savale

9. 3.DEAERATION:
• Air bubbles can interfere with the test results.
• Bubbles on the dosage unit may decrease the dissolution rate by
decreasing the available surface area.
• Some formulations will be sensitive to the presence of dissolved air in the
dissolution.
• Media containing surfactants are not usually deaerated after the
surfactant has been added to the medium.
• Media containing surfactants are not usually deaerated after the
surfactant has been added to the medium because of excessive foaming.
6/4/2016 9sagar kishor savale

10. 1.COMPENDIAL DISSOLUTION MEDIA:
• The traditional medium to simulate gastric conditions in the fasted state has been simulated
gastric fluid (SGF).
• This medium contains HCL and Nacl , as well as pepsin and water, and has a pH of 1.2.
• Although the medium addresses many of the qualities of gastric juice.
• For example, most studies of gastric pH indicate that the across-the-board average gastric pH
usually lies in the range1.5–1.9 .
Types Of Dissolution Media1
6/4/2016 10

11. •Water is an attractive medium that because of its simplicity has been
widely used for quality control purposes.
•It could even be argued that it is physiologically relevant since many
formulations are intended to be ingested with a glass of water.
•However, the pH of water may vary with its source, and water has no
buffer capacity.
6/4/2016 11sagar kishor savale

12. • A frequently used medium for the simulation of small intestinal (SI)
conditions in the fasted state is simulated intestinal fluid (SIF)
• A medium that was first described as standard test solution in the USP
more than 50 years ago.
• The only parameter that has been changed is the pH of the medium.
• As it was assumed that the pH in the small intestine is very close to blood
plasma, the pH of SIF was initially set at 7.5.
6/4/2016 12sagar kishor savale

13. As per above the 7.5 is mainly seen at the distal part so the we
can’t predict the whole intestine.
The dissolution characteristics of oral formulations should be evaluated over the
physiologic pH range of 1.2 -6.8.
6/4/2016 13sagar kishor savale

14. • From above we can say than the main difference seen in the
Stomach pH, this is due to the secreation of the gastric juice mainly
HCl.
• For very poorly soluble compounds, aqueous solutions may contain a
percentage of a surfactant (e.g., sodium lauryl sulfate, Tween 80,
Cremophor, Triton, terigitol , cyclodextrin or Span 80) that is used to
enhance drug solubility.
• The surfactant is added to mimic the action of the Bile salts
6/4/2016 14sagar kishor savale

15. •Biorelevant is short for ‘biologically
relevant’.
•Biorelevant media are virtually the same as
intestinal juices. They contain key natural
surfactants (bile salts, phospholipids)
present in intestinal juices. These are
missing from ordinary dissolution media.
•They are virtually the same as the fluids
inside the body, it can provide a much more
accurate picture of how drugs and their
formulations are likely to dissolve in vivo.
6/4/2016 15sagar kishor savale

16. • Several attempts have been made to improve simulation of fasting conditions in the
stomach. In most of these media, particular attention was given to the simulation of the
surface tension measured in human gastric aspirates.
• However, in these media, non-physiologically relevant surface active agents, lower than
physiological pH values or by far too high concentrations of pepsin or bile salts, were
utilized.
• Recently, a fasted state simulated gastric fluid (FaSSGF) containing pepsin and low
amounts of bile salt and lecithin was developed by Vertzoni .
6/4/2016 16sagar kishor savale

17. • Specifically fasted state simulating intestinal fluid (FaSSIF) was developed to simulate
fasting conditions in the proximal small intestine.
• The addition of a stable phosphate buffer system that results in a pH representative to
values measured from the mid-duodenum to the proximal ileum.
• This medium contains bile salts and phospholipids (lecithin).
• From pharmacokinetic studies of drug absorption in the fasted state , ingesting 200–250
ml of water with the dosage form, a maximum total volume of about 300–500 ml will be
available in the proximal SI. Therefore, for dissolution tests, a volume of ≤500 ml is
recommended.
6/4/2016 17sagar kishor savale

18. •Is the fed state, the luminal composition in the stomach will be highly dependent on
the composition of the meal ingested.
•The composition and the amount of the food is different in the every people , so we
can’t get correlation.
•The ideal medium representing initial gastric conditions in the fed state should have
similar nutritional and physicochemical properties to that of a meal, e.g., the standard
breakfast recommended by the USFDA to studying the effects of food in BA and
bioequivalence studies.
•Milk was first investigated as a dissolution medium about 20 years ago, the use of
Ensure® Plus has been established only a few years ago.
•Ensure® Plus have a similar composition to a breakfast meal with respect to the ratio
of carbohydrate/fat/protein.
•In addition, as the stability of fresh milk at 37°C is a problem, heat-treated milk must
be used.
6/4/2016 18sagar kishor savale

19. 1) http://www.pharmatutor.org/articles/review-selection-of-dissolution-media?page=0,2
6/4/2016 19sagar kishor savale

20. 6/4/2016 20sagar kishor savale