Drug Stability (IV) Lecture Notes PDF

Drug Stability (IV) Bahaa Mustafa, Ph.D. Pharmaceutics I (PSCI71303) 34 09/19/2024  Learning Objectives  Understand the Q10 method for shelf life determination.  Know the drug stability testing process.  Estimat...

Drug Stability (IV) Bahaa Mustafa, Ph.D. Pharmaceutics I (PSCI71303) 34 09/19/2024  Learning Objectives  Understand the Q10 method for shelf life determination.  Know the drug stability testing process.  Estimation of shelf life using Q10 method.  Discuss the stability testing protocols and frequency of testing. 35  Q10 Method (Shelf-Life Estimation)  The rate of a chemical reaction (including drug decomposition) depends on temperature (T).  It is generally accepted that a 10 ºC change in T gives a 3 times difference in the rate.  Q10 temperature coefficient: a measure of the rate of change of the chemical reaction as a consequence of the temperature being increased by 10 °C.  For most reactions, Q10= 3  For example: o K1 is the rate constant for a drug decomposition at T1 o The drug decomposition at T2 (T2=10+T1) will have a rate constant k2 (k2=3k1)  In other words, Q10 is the ratio of the two different reaction rate Degradation of powdered p-aminosalicylic acid in a dry atmosphere at elevated temperatures constants (Q10= k2/k1=3) when the difference in temperature is 10oC. 36  Q10 Method (Shelf-Life Estimation)  This method helps the compounding pharmacist to estimate shelf life for a product that has been stored or is going to be stored under a different set of conditions than specified in the product labeling.  For example, we can estimate the shelf life of product when stored at room temperature vs. under refrigeration.  Another example, if the expiration date is given for room temperature. What is the expected extension of the shelf life when the product is stored in a refrigerator?  It is also a useful tool for estimating the shelf life for real-time stability testing of a pharmaceutical product from elevated temperature studies (accelerated studies). 37  Q10 Method (Shelf-Life Estimation) T: absolute temperature (0oC=273K) ∆T=T2-T1 Q10=3 38  Q10 Method (Shelf-Life Estimation)  An increase in ∆T (T2>T1) will decrease the shelf-life, while a decrease in ∆T (T2T1) will shorten the shelf-life, and storing it at a cooler temperature (T2