# DISSOLUTION PROFILE by bmpatel7777

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PHARMAQUEST   1
CONTENTS :

1. Definition of dissolution profile
2. Importance of dissolution profile
3. Methods to compare dissolution profile
4. Dissolution studies of different dosage forms
I. Conventional
Powders
Tablet
Capsule
Suspensions
Suppository
Topical dosage forms
II. Controlled release
PHARMAQUEST   2
COMPARISON OF DISSOLUTION PROFILE HAS EXTENSIVE
APPLICATION THROUGHOUT THE PRODUCT DEVELOPMENT
PROCESS AND CAN BE USED TO……..

Develop in vivo- in vitro correlation which can help to reduce
cost and to speed up the product development.

DISSOLUTION PROFILE

It is graphical representation of …
Conc. Of dissolved drug Vs Time

PHARMAQUEST                  3
IMPORTANCE OF DISSOLUTION PROFILE

• Variation within same batch or between batch to batch

• Variation between brand to brand

• For optimizing the dosage formula by comparing the
dissolution profile of various formulas of the same A.P.I

PHARMAQUEST     4
METHODS TO COMPARE DISSOLUTION PROFILE

I.      Graphical method
II.     Statistical analysis
1. t – test
2. ANOVA
III.    Model dependent studies
1. Higuchi model
2. Hixon - Crowell model
IV.     Model independent studies
1. Similarity factor
2. Difference factor

PHARMAQUEST   5
120

% Metoprplol dissolved   100

80

60

40

20

0
5   10   15      20          25   30   45
Time in minutes
A    B     C      D
PHARMAQUEST             6
Statistical
analysis

t - test                             ANOVA

One sample   Paired     Unpaired
t- test
One way       Two way
t- test     t- test

PHARMAQUEST                  7
lX–ul           n

t =                    S

Steps to perform ANOVA

1. Calculate total sum of squares of variance (SST)
SST = ∑( xij - u)2
=   ∑ xij2 – T2/N        Where T= ∑xij
T2/N is called correction factor
u = ∑xij/N

2. Calculate Variance between Samples (SSC)
Sum of square between samples due to columns
SSC = h ∑(xij – u)2
= ∑Cj2/ h – T2/N        Where h = no. of rows
PHARMAQUEST               8
3. Calculate Variance within samples (SSE)
sum of squares within samples due to error
SSE = SST – SSC

4. Calculate F – Ratio
Fc = (SSC/ k-1) / (SSE/ N- k)

5. Compare Fc calculated with the FT ( table value)

PHARMAQUEST   9
DISSOLUTION STUDIS OF
DIFFERENT DOSAGE
FORMS
a) CONVENTIONAL
b) CONTROLLED
RELEASE

PHARMAQUEST   10
(A) CONVENTIONAL

 Powder
 Tablets And Capsules
        (Uncoated, Plain Coated)
 Suspension
 Suppositories
 Topical Preparations

PHARMAQUEST   11
Powders

   Powder particles dissolves independently of
each other
 First step in process of dissolution is wetting of
dissolving surface which is in contact with
dissolution medium.
 Intrinsic dissolution profile
 Apparatus - II can be used

PHARMAQUEST       12
Dissolution rate of dosage form which can be
explained by Noyes – Nernst equation

dC / dt = AD (Cs – C) / h V
Where, A = Surface area of the dissolving solid
D = Diffusion coefficient
h = Diffusion layer thickness
V = Volume of dissolution medium
Cs = Solute conc. in diffusion layer

PHARMAQUEST   13
TABLETS AND CAPSULES

 USP apparatus 1 and 2 are used

for dissolution of tablets and capsules.

PHARMAQUEST           14
DISSOLUTION OF TABLETS

 The rate of dissolution of drug substance from tablet
depends on the (1) solubility of the drug in that solvent
or gastric fluid and (2) the concentration of the drug in
the solution.

 Process variables also affect the dissolution rate of the
dosage form

PHARMAQUEST              15
Tablet           Disintegration           Granules           Deaggregation

Drug particles in
Suspension
Non -
Disintegrating
Drug in Solution in
GI Fluid

Drug in Blood

PHARMAQUEST                       16
Surface area Vs Time for different types of tablets

Non-disintegrating
tablets

Disintegrating
tablets
Fine particles
Surface
area
Disintegrated
granules
Solid

Time
PHARMAQUEST         17
Non disint. Tab.                      Rapidly disint. Tab

a                                   b
Slowly disint. Tab

c
Dissolved drug Vs Time for different type of tablets
PHARMAQUEST        18
DRUG IN      DISSOLUTION OF             DRUG IN
CAPSULE      CAPSULE SHELL              CAPSULE
MASS

DIFFUSION    DRUG PARTICLES
THROUGH
THE SHELL    IN SUSPENSION

DRUG IN
SOLUTION

DRUG
IN BLOOD

DISSOLUTION OF CAPSULE DOSAGE FORM
PHARMAQUEST             19
Different dissolution apparatus for tablet and
capsules
As per different pharmacopoeias

IP                  BP                                  USP

APPARATUS I AND II                FOR UNCOATED & PLAIN
II- BASKET TYPE                   TABLETS AND CAPSULES     EXTENDED
APPARATUS-I AND II       RELEASE AND
ENTERIC
COATED
APPARATUS
I, II AND III                               APP-III AND
III-Flow through cell
type                         PHARMAQUEST                   20
USAGE OF TABLET TO CALIBRATE APPARATUS

USP Prednisolone Tablets …….. Disintegrating

USP Salicylic acid Tablets ……… Non-
Disintegrating

PHARMAQUEST       21
NON-OFFICIAL METHODS FOR TABLETS

PHARMAQUEST   22
DISSOLUTION OF SUSPENSION

 Suspension and Post disintegrated tablet ……. Not same dissolution profile
 Problem with suspension : 1. Retention of dissolving material
2. Sampling problem

 Direct method : By electronic particle counting device for hydrocortisone
suspension
 Prednisolone acetate suspension have been evaluated for their dissolution
rates by employing the spin- filter device which provides magnetically driven
rotating filter system.
 Flow through apparatus has also been employed.

PHARMAQUEST                        23
DISSOLUTION OF SUPPOSITORY

PHARMAQUEST   24
BEAKER METHOD
METHOD

DIALYSIS CELL
METHOD
CONTINUOUS FLOW
METHOD
PHARMAQUEST              25
DISSOLUTION METHOD FOR SUPPOSITORIES

THERMOREGULATED              INSULATED RESERVIOR
WATER BATH    GLSS HEATING
COIL

SUPPOSITORY
FLOW-
THROUGH
-BED
CHABBER

GLASS

MAGNETIC STIRRER
PERISTALTIC PUMP                      PHARMAQUEST                                  26
Topical Dosage Forms

Official methods (USP)
-- APP- V (paddle) , VI (Cylinder)
And VII (Reciprocating holder)
Non-official methods
-- Diffusion through cellophane
Paper

PHARMAQUEST   27
SUPPORT TUBE

SAMPLE 2 Gms
500mL
BEAKER
WITH 400mL
MEMBRANE 0.8μm                                         WATER AT
30O

SUPPORT SCREEN
40- MESH STAINLESS

MAGNETIC
STIRRER

DISSOLUTION OF OINTMENTS
PHARMAQUEST                 28
Dissolution of controlled release
Dosage forms

FOR EXTENDED RELEASE AND
ENTERIC COATED

APP-III AND IV (USP)

PHARMAQUEST   29
Examples of using different dissolution apparatus for extended
release tablets in USP

Dissolution                 Example
Apparatus
Apparatus I                 Cefaclor extended release tablets

Apparatus II                Acetaminophen extended release
tablets

Apparatus VII               Nifedipine extended release tablets

PHARMAQUEST             30
Study Questions

1. Which are difficulties in dissolution study of suppositories
and suspensions
2. Discuss different methods of comparison of dissolution
profile
3. Discuss dissolution behaviour of tablet and capsules
4. Describe different dissolution apparatus for dissolution study
of suppositories

PHARMAQUEST       31
REFERENCES

 Pharmaceutical dissolution testing,
By Umesh V. Banakar P. No. 251

   Indian Pharmacopoeia -1996
   British Pharmacopoeia,24; 1993
   United States Pharmacopoeia
   JPS 58,10, 1267; 1969
   JPS 86, 6, 691;1995
   JPS,88, 9, 842-850;1999

PHARMAQUEST   32

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