Dissolution testing recap

Elena Kabova
e.kabova@reading.ac.uk
 Quality control tests
• Uniformity of (API) content - ensures desired API amount is delivered with
each dose
• Uniformity of weight – large variations indicative of problems
• Disintegration - different from dissolution!
• Dissolution
• Hardness – pressure required to break
the tablets
• Friability - ensures tablets withstand
the physical impact of manufacture,
packaging, and transport
1 2
• Appearance test
 Dissolution
Purpose – to study the dissolution rate of a formulation in specific conditions
For a drug to have a therapeutic affect, it must be in solution. Hence
the rate at which an API dissolves is of huge importance.

Procedure – Place the formulation in 1 L (known volume) liquid medium; take

sample at appropriate intervals and measure the UV absorbance of
the sample.

Calibration curve – Record the UV absorbance of known concentrations to establish a

relationship between concentration and UV reading.

Data manipulation – initial manipulation; adjustments for total volume

What did we do?

2 x Pure API (ibuprofen)

pH 1

2 x Ibuprofen tablets pH 7

2 x Ibuprofen sustain release capsules

2 x Ibuprofen liquid gel capsules (fast acting)

 Procedure
• All samples were placed in the dissolution baths.

• At specific time interval we draw a sample.

• The UV absorbance of the sample is measured.

• UV reading of the sample is used to calculate the pH 1

amount of API in solution.
pH 7
Data manipulation - Excel
• https://www.youtube.com/@excelforlifesci6702

• Simple excel manipulations – use data from BB document

The calibration curve
concentration mg/L Absorbance
500 0.799
400 0.639
300 0.48
200 0.336
100 0.179
50 0.077
0 0

0.9
0.8
0.7
f(x) = 0.00160733031674208 x
R² = 0.999581010332584
0.6
Absorbance

0.5
0.4
0.3
0.2
0.1
0
0 100 200 300 400 500 600
Concentration mg/L

Concentration = Absorbance /0.0016

 Dissolution – data manipulations
Time Absorbance
(minutes) pH 1

0 -0.011
5 -0.011
10 -0.011
15 0.004
20 0.017
30 0.027
40 0.033
50 0.038
60 0.045
80 0.046
100 0.045
120 0.047
 Dissolution – data manipulations
Time Absorbance Absorbance
(minutes) pH 1 pH 1 corrected

0 -0.011 0
5 -0.011 0
10 -0.011 0
15 0.004 0.015
20 0.017 0.028
30 0.027 0.038
40 0.033 0.044
50 0.038 0.049
60 0.045 0.056
80 0.046 0.057
100 0.045 0.056
120 0.047 0.058
 Dissolution – data manipulations
Time Absorbance Absorbance Concentration pH 1
(minutes) pH 1 pH 1 corrected mg/L

0 -0.011 0 0
5 -0.011 0 0
10 -0.011 0 0
15 0.004 0.015 9.375
20 0.017 0.028 17.5
30 0.027 0.038 23.75
40 0.033 0.044 27.5
50 0.038 0.049 30.625
60 0.045 0.056 35
80 0.046 0.057 35.625
100 0.045 0.056 35
120 0.047 0.058 36.25
 Dissolution – data manipulations
Time Absorbance Absorbance Concentration pH 1 % API dissolved pH 1
(minutes) pH 1 pH 1 corrected mg/L

0 -0.011 0 0 0
5 -0.011 0 0 0
10 -0.011 0 0 0
15 0.004 0.015 9.375 4.6875
20 0.017 0.028 17.5 8.75
30 0.027 0.038 23.75 11.875
40 0.033 0.044 27.5 13.75
50 0.038 0.049 30.625 15.3125
60 0.045 0.056 35 17.5
80 0.046 0.057 35.625 17.8125
100 0.045 0.056 35 17.5
120 0.047 0.058 36.25 18.125
 400
Dissolution - results
Considerations:
350
Powder
300
Sustain release • Conditions (pH7/1)
pH 7
Concentration (mg/L)

250
Liquid capsule • Formulation
200
Tablet
• Total amount of API
150

100

50
pH 1
0
0 20 40 60 80 100 120 140

-50
Time (minutes)
 Dissolution - results
350
120 LG
Powder 110 Powder
SR
300 SR 100
Tablet
90
250
Concentration (mg/L)

LG 80

% Dissolved API
200 70

Tablet 60
150
50

100 40

30

50
20

10
0
0 20 40 60 80 100 120
0
0 20 40 60 80 100 120 14
-50
Time (minutes) -10
Time (minutes)
 Dissolution – further considerations
Time Powder Tablet SR LG
Concentration Concentration Concentration Concentration
(mg/L) (mg/L) (mg/L) (mg/L)
10 300.6 6.9 33.1 20.6
30 325.7 131 181 183

Time Powder Tablet SR LG

% Concentration % Concentration % Concentration % Concentration

10 100.2 3.5 11.0 10.3

30 108.6 65.5 60.3 91.5
 Dissolution - results

120

100

80

60

40

20

0
1 2 3 4
Powder Tablet SR LG

Figure 1. The percent of API dissolved at 10 minutes (blue) and 30 minutes (orange) for the
four formulations at pH7.
Why do we have more than 100 % API?
 Dissolution - results

Concentration corrections

Usually, the removed volume for each sample would be replaced by an equal
amount. Corrections equations exist to account for the change in volume

Where: ν = volume removed (3 cm3) and V = total volume in the dissolution vessel
 Dissolution - Ibuprofen

How would you expect ibuprofen to behave in pH 1 and pH 7?

 Dissolution - questions
Question 1. The dissolution test was carried out in two different dissolution media.
Why?

Question 2. Report the calculation and describe the procedure that you would follow to
prepare 5 litres of 0.1 M HCl in water starting from a solution of HCl 1 M. In addition,
write down the formula that defines pH and calculate the pH of the solution 0.1 M HCl
acid?
 Dissolution - questions
Question 3. Perform the following calculations:
The buffer solution was prepared as described in the BP:
“Buffer Solution pH 7.0. To 1000 ml of a solution containing 1.8% w/v of disodium hydrogen
orthophosphate and 2.3% w/v of sodium chloride add sufficient (about 280 ml) of a solution
containing 0.78% w/v of sodium dihydrogen orthophosphate and 2.3 % w/v of sodium
chloride to adjust the pH. Dissolve in the solution sufficient sodium azide to give a 0.02% w/v
solution”. Express the following concentration in Molarity:
1.8 % w/v disodium hydrogen
orthophosphate
2.3 % w/v of sodium chloride

0.78 % w/v of sodium dihydrogen

orthophosphate
 Dissolution - questions
Question 4. Why is sodium azide used in the buffer?