1. SEMINAR ON…. In Vitro Dissolution Testing Models
Presented by : Saiesh P.Phaldesai st year M.Pharm Dept. of pharmaceutics Srinivas college of pharmacy
Mangalore

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 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
Reciprocating disk
Rotating disk (non USP –NF)
Extended realese drug products(Beads)

6. INVITRO DISSOLUTION TESTING.
Rotating basket method.
Cylindrical basket of 22mesh.
Rotating speed-100 rpm.
As per IP height of dissolution jar is mm and internal diameter is mm and height of basket mm and diameter is 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 mm
Position & alignment of the paddle are specified in USP same set of standards for calibration.
Temp at 37 ۠c.
Very sensitive to tilting.
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
Reciprocating frequency is about 30cylces per minute.

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

17. Disadvantage Clogging of basket screen by gummy particles
Tendency of a light particles to float at surface after leaving baskets or in paddle method
Sensitivity of apparatus to variables such as vibrations, eccentricity.
Rapid corrosion of SS mesh in presence of HCl
Sensitivity of apparatus to any slight changes in paddle orientation
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
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 Rotating disk 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. Intrinsic dissolution method
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.

35. Thank You...