Chemical Kientics And Drug Stabilit

Question 1

What is a drugs shelf life?

Answer 1

The period of time during which, if stored correctly is expected to retain acceptable stability

The standard amount of degradation is 10%. Meaning the drug is at 90% of its original content

Question 2

What does it mean if a drug is adulterated?

Answer 2

If the product contains unacceptable levels of degradation products

**this can happen as the drug starts to expire. Degradation products are a by product of the pill breaking down

Question 3

What does it mean if a product is misbranded?

Answer 3

The product does not have the labeling for appropriate storage conditions

Question 4

What are the chemical mechanisms of degradation?

Answer 4

Separation of chemical compound into simpler compounds, changing chemical nature

Solvolysis (hydrolysis)

Oxidation-reduction (redox)

Photolysis

Isomerization / racemization

Question 5

What are the physical mechanisms of degradation?

Answer 5

Polymorphism

Vaporization

Absorption

Question 6

What is Solvolysis?

Answer 6

It’s a form of chemical degradation

It’s the decomposition of active drug thro rxn with a solvent

**Most common mechanism and the solvent is usually water (hydrolysis)

This is the reason why you don’t keep your drugs in the fridge

(Drugs with function groups are most susceptible, aspirin, procaine, beta-lactams)

Question 7

How can you help to prevent hydrolysis?

Answer 7

1. Refrigeration (less moisture in fridge)
2. For solids (use desiccant packets, add water proof coating to pills)
3. For liquids (replace water for another less reactive solvent, mess with pH, put drug into micelles, USE powders that you reconstitute before you dispense them)

Question 8

What is an oxidation-reduction rxn (redox)?

Answer 8

Oxygen is usually involved

These happen spontaneously (this is what happens when you cut an avocado)

Question 9

How can you prevent redox rxn?

Answer 9

1. Oxygen affects it so you can purge the headspace of a container with N2 or CO2
2. PH affects it so you can add a buffer to change the pH an keep redox to a minimum
3. Temp affects it. Keep it at cooler temps
4. Presence of catalysts. Add a chelatng agent (these will bind to trace metals which act like catalysts) EDTA, citric acid, tartaric acid)
5. Include antioxidants. These will find to free radicals which can oxygen and prevent them from causing the redox rxn (these are suicide molecules, that have a higher affinity to the radials and bind at a higher rate so it wont react to the product)

Question 10

What is Photolysis?

Answer 10

It’s a chemical rxn that occurs as a result of exposure to radiation in the form of light. UV light

Ex: riboflavin, phenothiazines

**how can you prevent it? Put the drugs in a container that will block the UV radiation. Or coat the tablets

Question 11

What is isomerization?

Answer 11

It’s when the chemical formulation is the same but it has a different rotation and becomes optically different.

Cis or trans molecules. Some drugs work better in specific isomerization so when they degrade you might get more trans molecules when the cis is actually the more active. This would lead to the drug not functioning correctly

Question 12

What is polymorphism?

Answer 12

Different solid crystalline forms of the same chemical entity

These polymorphisms have different crystal energies, and over time they will go from highest energy form (least stable) and revert back to lower energy (more stable) polymorphism

Question 13

What is vaporization?

Answer 13

Not a major route of degradation

Only some drugs are effected by this (nitroglycerin)

It’s when the drug molecules are lost as vapor from solid ( sublimation, means you go from solid state to a vapor state and skip the liquid form)

Question 14

What is absorption in terms of degradation?

Answer 14

Molecules of the drug or other components may be lost from a formulation by “sticking to” the surface of a container

*happens with plastic and rubber

***how to prevent, change containers (glass) or change dosage forms

Question 15

What order of reaction is INDEPENDENT of drug amount?

Answer 15

Zero-order

This means that no matter the amount of drug the rate of degradation (Kz) will not change

Question 16

What order of reaction is DEPENDENT on the amount of drug present at any given point?

Answer 16

First-order

This means that depending on the amount of drug left your rate of degradation will change

Question 17

What is the equation for zero-order reactions?

Answer 17

At = Ao - Kz(t)

At = amt of drug at time t

Ao = amt of drug at t=0

Kz= zero order degradation constant

T = time

Question 18

What is the equation for half life of zero order reaction?

Answer 18

t1/2 = .5Ao / Kz

Question 19

What is the equation for shelf life in zero order reactions?

Answer 19

For 10% degradation it would be

.1Ao / Kz

For 20% it would be

.2Ao / Kz

Question 20

What is the equation for first order reactions?

Answer 20

Ln At = ln Ao - Kf(t)

Question 21

What is the equation for half-life when it comes to first order reactions?

Answer 21

T1/2 = ln(2) / Kf

Question 22

What is the shelf-life equation for first order reactions?

Answer 22

For 10% degradation it would be

Tshelf = ln(1/.9) / Kf

For 20% degradation it would be

Tshelf = ln(1/.8) / Kf

Question 23

What kind of reaction does you body usually follow during elimination

Answer 23

Usually follows first order process

Question 24

When it comes to absorption of drugs in the body which kind of drugs follow zero order and which ones follow first order?

Answer 24

Zero - usually for controlled release products or patches

First - applies to a lot of conventional dosage forms; solutions, regular tablets , caps