DETERMINATION OF INTRINSIC DISSOLUTION

RATE OF SALICYLIC ACID

Aim: To determine the INTRINSIC DISSOLUTION RATE (IDR)

of salicylic acid.

Objective:
1) To study the dissolution profile of salicylic acid pellet at
standard conditions.
2) To estimate the amount of drug which might be available for
absorption.

Definition: The intrinsic dissolution rate is defined as the rate of

dissolution of a pure pharmaceutical active ingredient when
conditions such as surface area, temperature, agitation or stirring
speed, pH, and ionic strength of the dissolution medium are kept
constant.
FORMULA: IDR=SLOPE/S.A
Where slope means slope of the graph plotted
between cumulative amt of drug released vs time.
S.A is the surface area of exposed surface of the pellet.
UNITS: mg/min/cm²
Theory: The measurement of IDR is a tool in the functionality &
characterization of bulk drug substances. The dissolution rate &
bioavailability of a drug are influenced by its solid state properties
(ex: crystallinity, hydration, solvation, particle size, particle
surface area etc). The measured IDR is dependent on these solid
state properties.
During the preformulation stage, an understanding of the
dissolution rate of drug candidate is necessary since this property
of the compound is recognized as significant factor involved in
drug bioavailability.
The major factor that determine dissolution rate is the
aqueous solubility of the compound however other factors such as
particle size, crystalline state, Ph and buffer concentration can
affect the rate.5
Determining this parameter allows the screening of drug
candidates and aids in understanding their solution behaviour
under various biophysiological conditions.1
The evaluation of the intrinsic dissolution of active
pharmaceutical ingredients (APIs) is a means to demonstrate
chemical purity and equivalency. The need to demonstrate
sameness among APIs has risen because of changes in
 bulk active synthesis
 final crystallization steps
 particle size and surface area
 polymorphism scale-up issues regarding batch size and
manufacturing site.2
APPARATUS USED FOR DETERMINATION OF
INTRINSIC DISSOLUTION RATE:
Two intrinsic dissolution apparatuses and kits were used.
Table I compares the key features, strengths, and weaknesses of
the two systems. All of the dissolution experiments were
performed with the model 2100B dissolution system and the model
2230 auto sampler from Distek, Inc. (North Brunswick, NJ).
1) Rotating disk system (USP Wood apparatus):
The rotating pellet or disk system used was the Wood
apparatus from VanKel Industries,Inc. (Cary, NC).The apparatus
consists of a steel punch, a die, and a base plate (3,4).
The base of the die has three threaded holes for the insertion
of screws and the attachment to the base plate. Test material was
placed in the 0.8-cm (0.315-in.) diameter die cavity.
The punch was inserted into the cavity and compressed with
the aid of a bench top Carver press for 4–5 min at 2000 psi. The
base plate was then disconnected from the die to expose a smooth,
compact pellet with a 0.5-cm2 surface area.
A Neoprene gasket was placed around the threaded shoulder
of the die, which was then screwed onto the shaft holder, and the
shaft was mounted on the stirring drive mechanism of the
dissolution apparatus.
Once all six shafts were mounted, the dies were lowered into
the dissolution vessel (curved bottom) containing 900 mL of
dissolution medium at 370C.
The distance of the die face from the bottom of the vessel
was set at 1 in. Dissolution was performed at 50 rpm. At
appropriate time intervals, an automated sample collector removed
aliquots from the dissolution medium.
2) Stationary disk system :
The apparatus consists of a steel punch, a die, and a base
plate. The die base has three holes for the attachment of the base
plate. The three fixed screws on the base plate are inserted through
the three holes on the die and then fastened with the three supplied
washers and nuts.
Test material was placed in the 0.8cm (0.315-in.) diameter
die cavity. The punch was then inserted into the cavity and
compressed with the aid of a bench top Carver press for 4–5 min at
2000psi.
The base plate was then disconnected from the die to expose
a smooth, compact pellet with a surface area of 0.5 cm2. AViton
gasket was placed around the threaded shoulder of the die, and a
polypropylene cap then was screwed onto the threaded shoulder.
The assembly was next immersed, pellet side up, into the
bottom of the dissolution vessel (flat bottom) containing 900 mL of
dissolution medium at 370C.
A pair of forceps was used for this operation, and six dies
were placed within 30 s. The dimensions of the flat portion at the
bottom of the dissolution vessel permit the die assembly to settle in
a horizontal position and without shifting during the stirring of the
dissolution medium.
 The USP Apparatus 2 paddle was the stirring mechanism for
the dissolution system. The bottom of the stirring paddle was 1 in.
from the die face. Dissolution was performed at 50 rpm. Again, at
appropriate time intervals, an automated sample collector removed
aliquots from the dissolution medium.

Comparison of the rotating and stationary disk systems.

Feature Rotating Disk System Stationary Disk System

Operation Rotating or forced shear like dissolution opretion. Static or solvent shear-like dissolution
Similar to USP procedure I. Dissolution is operation. Similar to USP Procedure II.
achieved by shear-like motion of the pellet in the Dissolution is achieved by moving a
dissolution medium. Pellet faces down. volume of dissolution medium over the

pellet. Pellet faces up.

Dissolution Designed for apparatus similar to the VanKel Used with USP Apparatus 2 paddles on
testing station VK7000 module. any dissolution module.

Dissolution Standard, curved-bottom 1-L beaker. Flat-bottom, 1-L beaker. The flat
vessel surface diameter is 5.38 cm (2.12 in.)

Shaft design Stainless steel rod with hollow die holder Uses standard paddle from USP
Apparatus 2. Die holder acts as a
plastic screw cap and base.

Introduction of Pellet and die assembly is introduced into the Pellet and die assembly is introduced
compact pellet dissolution medium all at once, when the into the dissolution medium one at a
into the dissolution drive mechanism is lowered. time with the aid of a pair of forceps.
dissolution
medium

Die weight 515 g 144 g

Die height 3.54 cm 1.27 cm

Die diameter 5.38 cm 5.38 cm

Die cavity 0.8 cm/0.5 cm2 0.8 cm/0.5 cm2

diameter/area

Recommended 50 rpm 50 and 100 rpm

speed

Comparison of dissolution profiles.

 The cumulative amount of drug substance dissolved at any
time point is the product of the drug concentration in the sample
and the volume of media. Intrinsic dissolution takes into account
the correction factor for reduced volume, whereby the amount of
drug substance contained in each sample volume is added back to
the cumulative amount at subsequent time points 6.
The amount of drug dissolved per unit area is plotted against
time. The slope of the line is the intrinsic dissolution rate in
milligrams per square centimeter per minute.
USP recommends that the earlier time points be used in the
calculation of slope. Based on our experience, the use of at least
five points from the earlier segment of the dissolution curve will
provide meaningful data.
The similarity factor f2 compares the dissolution profiles for
each compound tested by both apparatuses. The equation used in
calculation is

f2=50 log {[1+(1/n)∑tn=1(Rt-Tt)2]-1/2.100}

Reference:
Gibson, pg no-84
Remington 21st, volume 1st, pg no. 673

Requirements: salicylic acid powder AR, ethanol, magnesium

stearate, distilled water, glass slide, pelleting machine, dissolution
apparatus, hot plate, test tubes, pipettes, wax, uv-visible
spectrophotometer etc.

Procedure: It involves the following steps

1) Preparation of salicylic acid pellet:

a) Weigh 200mg of salicylic acid.
b) Prepare 5% magnesium stearate solution (10ml) in ethanol.
c) Lubricate the punch & die with magnesium stearate
solution.
 d) Pour powder into the die cavity & fix the assembly into the
punching machine.
e) Apply vacuum for 2min.
f) Apply pressure of 10 tons for 2min.
g) Then stop the vacuum & release the pressure.
h) Collect the pellet & weigh it.

2) Covering the pellet surface with wax leaving one surface

free:
a) Take wax in a beaker & melt on a hot plate.
b) Pour the melted wax on the glass slide & place the pellet
carefully on that wax layer.
Note: see that the sides & base are coated completely except the
top surface.

3) Setting of dissolution apparatus:

a) Take 900ml of water in the dissolution apparatus.
b) Adjust the temperature to 37°C & paddle speed to
100rpm.

4) Experiment:
a) Place the glass slide (with pellet) carefully into the
apparatus & start the apparatus.
b) Collect 10ml of sample from the cup every 15min & at the
same time replace it with 10ml of water every time into the
cup.
c) Samples are collected till the 90min time.
d) Determine the absorbance values for the collected samples
by using uv-visible spectrophotometer at 296.4nm.
Note: If the absorbance values come greater than 0.8 then dilute
the sample & then check the absorbance values.
5) Observations:

S.No Time (in min) Absorbance

1 15 0.2819
2 30 0.5561
3 45 0.8162
4 60 0.3087(1:5)
5 75 0.3697
6 90 0.434

6) Calculation of concentrations at different time intervals by

using calibration curve:
Concentrations of the collected samples were determined with the
help of this data obtained from calibration curve.

Preparation of std curve of salicylic acid:

S.No Conc(µg/ Absorban

ml) ce
1 5 0.1473
2 10 0.262
3 15 0.4224
4 20 0.5227
5 25 0.6867
 Standard curve:

Determination of IDR:

S.N time Absorban Conc Conc mg/900 Cum Amt mg/sq.cm

o ce (ug/ml) (ug/10ml) ml after time
t
1 15 0.2819 10.842307 108.4230769 9.7580 9.758 7.3553687
7 77 86
2 30 0.5561 21.388461 213.8846154 19.249 19.358038 14.591669
5 62 46 59
3 45 0.8162 31.392307 313.9230769 28.253 28.466961 21.457778
7 08 54 27
4 60 1.5435 59.365384 593.6538462 53.428 53.742769 40.510133
6 85 23 97
5 75 1.8485 71.096153 710.9615385 63.986 64.580192 48.679148
8 54 31 46
6 90 2.17 83.461538 834.6153846 75.115 75.826346 57.156255
5 38 15 35

As we know from the formula that the cumulative amount of the drug
released from per unit surface area per unit time gives the IDR so here slope
of the above graph gives the IDR.
Result:
The INTRINSIC DISSOLUTION RATE of salicylic acid was found to be
0.705 mg/cm2/min.