DISSOLUTION APPARATUS AS PER IP and USP

1. SEMINAR ON….
In Vitro Dissolution Testing
Models
Presented by :
Ram Kumar
4th year B.Pharm.
ISF college of pharmacy
Moga.

2. CONTENTS
 Introduction.
 Need for dissolution testing.
 In vitro dissolution testing models.
 In vitro - In vivo correlation.
 References.

3. NEED FOR DISSOLUTION TESTING
 Evaluation of Bio availability.
 Development of more efficacious and
therapeutically optimal dosage forms.
 Minimizes use of humans as test subjects
 Ensures quality of the product
 Correlation between dissolution results &
bioavailability of product between batches.
 Product development, quality control and
research and application.
 Screening of formulations during product
development .

4. Official dissolution rate test apparatus
App no IP BP USP
1 Paddle Basket Rotating basket
2 Basket Paddle Paddle
3 Flow through cell Reciprocating cylinder
4 Flow through cell
5 Paddle over disk
6 Rotating cylinder
7 Reciprocating disk

5. Name of Apparatus Drug Product
Rotating basket Tablets
Paddle Tablets, Capsules, Modified release
products, Suspensions
Reciprocating Cylinder Extended release drug products
Flow cell Low water soluble drugs
Paddle over disk Transdermal drug products
Cylinder Transdermal drug products
Reciprocating disk Extended release drug products
Rotating disk (non USP –NF) Extended realese drug products(Beads)

6. INVITRO DISSOLUTION TESTING.
1) Rotating basket method.
 Cylindrical basket of 22mesh.
 Rotating speed-100 rpm.
 As per IP height of dissolution jar is 168+8 mm and
internal diameter is 102+4 mm and height of basket
36.8+3 mm and diameter is 25.4+3 mm
 Temp. maintained at 37 ̇ c
 Calibration tablets of Prednisone-for disintegrating
tablets.
 Salicylic acid calibration tablets-for non
disintegrating tablets.
 For capsules & dosage forms that tend to float.

8. 2) Paddle method.
 Teflon coated paddle to minimizes turbulence
due to stirring.
 Vertically attached.
 As per IP diameter of the paddle is 74.5+0.5 mm
 Position & alignment of the paddle are specified
in USP same set of standards for calibration.
 Temp at 37 ۠c.
 Very sensitive to tilting.
 2 - 50 rpm-for solid oral dosage forms, 25 rpm-
suspensions.
 For tablets, capsules, suspensions.
 Few turns of platinum wire as a Sinker .

10. 3) Reciprocating cylinder method.
 Set of cylindrical, flat –bottomed glass vessels
equipped with reciprocating cylinders
 For testing of extended release products and for
beads.
 temp. 37۠ c.

12. 4) Flow through cell method
 Reservoir of medium
 Pump that forcing medium through the cell
holding test sample
 Flow rate from 4 to 16 mL/min.
 For modified release dosage forms, containing
active ingredients with limited solubility.
 Laminar flow by pulse less pump
 Dissolution medium may be fresh or recirculated
 Fresh medium ,dissolution rate at any moment
can be obtained.

13. Flow through cell

14. 5) Paddle over disk method
 Sample holder or disk assembly that holds
the product.
 Temperature -32oC.
 Paddle is placed over the disk assembly.
 Sample drawn midway between the surface
of the dissolution medium and the top of the
paddle blade.
 For testing the release of drug from
transdermal products.

15. 6) Rotating cylinder method
 A stainless steel cylinder is used to hold the
sample.
 Sample is mounted on to cuprophan.
 Temperature 32oC.
 For testing transdermal preparations.
7) Reciprocating disk method
 A motor drive assembly is used to reciprocate
the system vertically.
 Samples are placed on disk shaped holders
using cuprophan supports
 Temperature 32oC.
 Reciprocating frequency is about 30cylces per
minute.

16.  Advantages of official methods
1. Better reproducibility
2. For capsules as they tend to float at
surface thus minimizing area exposed
to dissolution fluid

17.  Disadvantage
1. Clogging of basket screen by gummy particles
2. Tendency of a light particles to float at surface
after leaving baskets or in paddle method
3. Sensitivity of apparatus to variables such as
vibrations, eccentricity.
4. Rapid corrosion of SS mesh in presence of HCl
5. Sensitivity of apparatus to any slight changes in
paddle orientation
6. Non reproducible position of tablet at bottom of
flask

18. Dissolution acceptance:
stage Number tested Acceptance criteria
S1 6 Each unit is not less than D+5%
S2 6
average of a 12 units(S1+ S2) is equal to or greater
than D and no unit is less than D+15%
S3 12
Average of 24 units (S1+
S2+ S3) is equal to or greater than D not more than 2
units are less than D +15% and no unit is less than D
+25%
where D is amount of dissolve active ingredients expressed in % in individual monograph

19. Non official methods
 Tumbling method
 Rotating disk method
 Rotating bottle method
 Intrinsic dissolution method
 Peristalsis method
 Sartorius apparatus
 Beaker method
 Dialysis method

20. Tumbling method
 In this method dosage form is placed in tubes or
bottles which are rotated using revolving drum
Rotating disk method
 Developed by late eino nelson and described by Levy
and Sahli.
 Non disintegrating tablets or discs mounted in
plexiglas holder, one surface exposed to the
dissolution medium
 Holder is attached to the metal shaft ,free from
vibration
 The tablet immersed one inch below the surface of
200 ml of dissolution fluid , temp 37 ۠c , in 500 ml
three nacked round bottom flask , rate is 550 rpm.
 Samples were taken and assayed for drug content.

21. Rotating filter method
 It consists of magnetically driven rotating
filter assembly and a 12 mesh wire cloth
basket in which dosage form is placed
 The sample is withdrawn through
spinning filter for analysis
Sartorius apparatus
 It utilize in vivo stimulative method
 The absorption stimulater stimulates
passive drug transport process that occur
in vivo from GIT tract to plasma across
lipoidal mucosal barrier

22. Rotating bottle method
 It consists of rotating rack to hold sample drug
products in bottles and they are capped tightly
rotated in 370c temperature bath
 Sample are decanted through a 40 mesh
screen and residue are assayed.
Intrinsic dissolution method
 Most method for dissolution deal with finished
drug product
 The dissolution of drug powder by maintaining
constant surface area is called intrinsic
dissolution.
 It is expressed as mg/cm2 /min.

23. Peristalsis method
 To stimulate hydrodynamic condition of GIT tract
in an in vitro dissolution device.
 It consists of rigid plastic cylindrical tubing fitted
with septum and rubber stopper at both ends.
 Dissolution chamber consist of a space between
the septum and the lower stopper
 Dissolution medium pumped with peristaltic action
through the dosage form

24. Beaker method
 Reported by Levy and Hayes(1960)
 Dissolution medium , 250 ml of 0.1 N HCl at
37۠ c placed in a 400 ml beaker
 Agitation by three blade polyethylene
stirrer,5 cm diameter and rotates at 60 rpm.
 Stirrer immersed to a depth of 2.7 cm in
medium and in the center
 Samples are removed and assayed for the
content.

25. Dialysis methods
 Cell consist of 32 mm inflated membrane
 Plugged at the lower end by tight fitting cylindrical
perspex box.
 Upper end of the tube held by thin perspex ring
inserted into the tube and secured by an elastic
band
 The cell , suspended from the arm of a tablet
disintegration apparatus and containing the
dosage form in 50 ml of distilled water at 37 ۠ c

26.  The cell was raised and lowered 30 times a min
into 150 ml of distilled water at same temp.
 Agitation by slight flexing and streching of the
dialysis membrane as it enters and leave the bath
 Rotation at 60 rpm
 Samples taken and assayed for content.

27. INVITRO-INVIVO CO-RELLATION
The FDA regulations of 1977 on bioavailability and bioequivalence
stated that dissolution test, the preferred in-vitro test should be co-
related with the in vivo data.
 Biopharmaceutics drug classification system.
Theoretical basis for correlation.
JW= PWCW
JW Drug flux through intestinal wall at any position & time
PW permeability of the membrane
CW drug concentration at the intestinal membrane surface

29. DISSOLUTION RATE Vs ABSORPTION RATE
 Absorption time - In correlating dissolution data to absorption
data
 It refers to the time for a constant amount of drug to be
absorbed
 Correlation between time required for a given drug to be
absorbed &time required for the same amount of drug to be
dissolved in vitro for three sustained release aspirin products.
 The results from this study demonstrated that aspirin was
rapidly absorbed and was very much dependent on the
dissolution rate for absorption.

30. PERCENT OF DRUG DISSOLVED Vs PERCENT OF DRUG
ABSORBED
 One must consider Appropriate dissolution medium
 Slow dissolution stirring rate
 An example of continuous in vitro-in vivo correlation of
aspirin

31. MAXIMUM PLASMA CONCENTRATIONS Vs PERCENT OF
DRUG DISSOLVED IN-VITRO
 Different drug formulations
 Poorly formulated drugs-incomplete dissolution,
release –lower plasma drug concentration
 Peak drug serum concentration is higher for the
drug product that shows the highest percent of
drug dissolved

32. In-vitro in-vivo correlation for 100mg Phenytoin sodium capsule is
shown the graph

33. SERUM DRUG CONCENTRATION Vs PERCENT OF DRUG
DISSOLVED
 Simulated gastric juice
 In vivo in vitro correlation between10 minute serum level
and dissolved at 1.2 minutes (o) & the 20 minute serum
level and percent dissolved 4.2 minutes (●)

34. REFERENCES
 Dissolution, bioavailability & bioequivalence by,
Hameed M. Abdou.
 Biopharmaceutics & clinical pharmacokinetics by,
Milo Gibaldi.
 Applied Biopharmaceutics & clinical pharmacokinetics by,
Leon Shargel /Andrew B. C. Yu
 Pharmaceutical dissolution testing by,
Banker, Dekker series.
 Biopharmaceutics & pharmacokinetics by,
G.R. Chatwal.
 Biopharmaceutics & pharmacokinetics – A treatise
D.M.Brahmankar, Sunil B. Jaiswal.
 www.google.com