Exam 3- Lecture 3: Q10 & Mean Kinetic Temperature

What can the Arrhenius relationship & its applied kinetics help us predict?

Degradation rxn rate at low temperatures where it may not be feasible to perform precise analytical measurements based on rate constant data rather we have collected from higher temperatures

What have understanding b/w come from from studied chemical degradation?

Drugs degrading by common mechanisms like oxidation or hydrolysis is adequate

What can we use average sensitivity of most rxns to temperature to guess?

What possible effect on stability will be for drug that hasn’t been studied before

What do the 3 lines represent?

Least, average, & most sensitive rxns leading to a prediction interval likely to capture actual kinetic behavior for drug at lower temperature

What can the Arrhenius kinetics provide a mechanism by which we can predict?

Stability at one temperature based on stability at another temprature

What can be used to calculate rxn’s rate constant at any temprature?

Frequency factor (A) & activation energy (Ea)

What can we use the ratio b/w rxn rate at 2 temperatures such that?

Ratio only depends on activation energy & temprature change

How can we further simplify this relationship further to reflect?

A change of 10C & use it as reference value called Q10

What does Q10 describe?

Factor by which a molecule’s stability will change when temprature is changed by 10C (if a drug has Q10 of 3, changing storage conditions from 20 to 30 degrees will make drug 3 times less stable)

What will benchmark time or shelf-life will always while there are differences benchmark times of rxns w/ different rxn orders?

Inversely proportional to rxn’s rate constant

What does Q10 therefore tell us?

Not only how many times larger rate constant will be, but also how many times shorter benchmark time will be (If Q10 equals 4, rate constant will be 4 times larger, & time required to lose 15% of initial concentration will 4 times shorter when temperature is changed by 10 degrees)

What happens when temperature changes by more than or less than 10 hours?

Relationship b/w temperature & rxn kinetics is exponential

What is change in stability not directly proportional to?

Temperature change b/c stability is exponentially proportional to temprature change

What can we mathematically capture the exponential relationship b/w?

Stability & temperature as follows to encompass temperature changes greater than 10 hours

What is a somewhat common occurrence in pharmacy practice happen when?

A drug product experiences multiple different storage temperatures for prolonged periods of time

What are the most common storage conditions?

• Controlled room temperature (CRT)

  • 20-25C

• Refrigerated

  • 2-8C

What about excersions outside the listed ranges while these conditions are more specific than previously used ambiguous recommendations?

Do not disqualify a product from being used

What can drugs recommended for CRT shift in storage temperatures?

Above 25C are okay as long as stay below 30C & spikes up to 40C are allowable as long as they last less than 1 day

What is the product’s average storage temps across any temp fluctuations conventionally?

Required to not deviate from labeled conditions even if product experiences a temperature outside of the recommended for some period

What is mean kinetic temperature (MKT)?

A single calculated temperature that represents the overall effect of fluctuating temperatures on drug stability over time

What is the MKT similar to?

Other means or averages b/c actual temp will vary both above & below the MKT but w/ the distinction that MKT is weighted toward higher temps

What will the MKT almost always be larger than?

True average of different temps a product might be stored at