Estimation of Shelf Life under Temperature Fluctuating Conditions

Actual storage temperature of pharmaceuticals fluctuates with time. The degradation rate at fluctuating temperatures is higher than that at the average temperature. The difference is determined by the fluctuation pattern and activation energy for the degradation reac-tion.778-780 For example, the degradation rate of a reaction under a temperature cycle represented by a sine curve with an average of 20°C and a range of 10°C (Fig. 199) is 1.08 times larger than that at a constant temperature of 20°C (for a reaction with an activation energy of 20 kcal/mol).

The concept of average kinetic temperature ( T) was introduced by Haynes781 to predict the stability of pharmaceuticals stored under fluctuating temperature conditions over the course of a year. Tk is represented by Eq. (4.12) using month-average temperatures from

Figure 198. Effect of activation energy and assay error on the probability that all the values of degradation percentage observed after a storage at 40°C for 2,4, and 6 months are less than 10%. Assay error (standard deviation): -, 0.5; — .— 1;---, 1.5; ■■■, 2%. (Reproduced from Ref. 777 with permission.)

Figure 198. Effect of activation energy and assay error on the probability that all the values of degradation percentage observed after a storage at 40°C for 2,4, and 6 months are less than 10%. Assay error (standard deviation): -, 0.5; — .— 1;---, 1.5; ■■■, 2%. (Reproduced from Ref. 777 with permission.)

January to December ( T to Tu) and corresponds to a "virtual" temperature at which a product would undergo degradation at the same rate as a product exposed to the fluctuating temperature pattern. Table 2 shows the values of T for various cities as a function of Ea values. Note that these critical temperature values vary most significantly from the average temperature values for those cities with the biggest temperature fluctuations and for reactions with higher Ea values.

Table 12. Average Kinetic Temperatures of Various Cities for Reactions with Different Activation

Energies

Average kinetic temperature for a reaction with an activation energy (kcal/mol) of:

Table 12. Average Kinetic Temperatures of Various Cities for Reactions with Different Activation

Energies

City

Average temperature"

10

20

30

Sapporo

8.2

10.4

12.5

14.0

Sendai

11.9

13.6

15.2

16.5

Tokyo

15.6

17.0

18.5

19.7

Osaka

16.3

17.9

19.5

20.8

Kagoshima

17.6

18.9

20.2

21.3

Naha

22.4

22.9

23.4

23.9

Oslo

3.8

5.6

7.4

8.7

Berlin

9.4

10.7

11.9

13.0

London

9.7

10.3

10.9

11.5

Beijing

11.8

14.7

17.2

18.8

Washington, D.C.

14.3

16.2

18.1

19.4

Rome

15.5

16.3

17.2

18.0

Sydney

17.9

18.2

18.6

19.0

Rio de Janeiro

23.8

23.9

24.0

24.1

Djakarta

27.2

21.2

21.2

27.2

Manila

27.4

27.4

27.4

27.5

Bombay

27.5

21.5

27.6

27.1

Bankok

28.4

28.5

28.5

28.6

Djibouti

29.5

29.8

30.2

30.6

" Average over the period 1961-1990.

" Average over the period 1961-1990.

An alternative to the concept of average kinetic temperature is the kinetic ratio ( a) , a ratio of a rate constant at a fluctuating temperature to that at a standard temperature, exp

Was this article helpful?

0 0
Drug Addiction

Drug Addiction

If you're wanting to learn about drug addiction... Then this may be the most important letter you'll ever read You Are Going To Get A In Depth Look At One Of The Most Noteworthy Guides On Drug Addiction There Is Available On The Market Today. It Doesn't Matter If You Are Just For The First Time Looking For Answers On Drug Addiction, This Guide Will Get You On The Right Track.

Get My Free Ebook


Post a comment