ASE201 Drug Delivery Systems: Product Stability

This set of flashcards covers factors affecting drug and product stability, degradation mechanisms (hydrolysis, oxidation, photolysis), temperature effects via the Arrhenius equation, and regulatory requirements for stability testing.

What are the ideal shelf-life and potency requirements for pharmaceutical products?

A shelf-life of at least $3\,\text{years}$ with no less than $95\,\%$ potency.

How is kaolin classified according to drug stability?

Stable at all conditions.

What are the four main drug degradation processes?

Oxidation, Photolysis, Hydrolysis and Trace Metal Catalysis.

What is the definition of shelf-life ($t_{95}$)?

The duration or the point of time that 5% of drug degradation occurs, preferrably within a minimum of 3 years.

What is the effect of a $10^{\circ}C$ increase in temperature on the rate of decay?

It typically increases decay by $2-5\,\text{folds}$.

Which equation is used to show the relationship between temperature and the rate of reaction during accelerated stability testing?

The Arrhenius equation: $k = Ae^{-Ea/RT}$.

What is the difference between Hydrolysis and Solvolysis?

Hydrolysis is the chemical breakdown of molecules with water, while solvolysis is the breakdown with a solvent.

Which chemical conditions catalyze breakdown via hydrolysis?

The presence of $OH^{-}$, $H_{3}O^{+}$, heat + light, and high drug concentration.

What is the recommended solution to prevent oxidation in a drug formulation?

Add antioxidants to reduce or prevent oxidative degradation.

Why does UV light cause more molecular energy increase compared to visible light in photolysis?

Because UV light has a shorter radiation wavelength, and shorter wavelengths result in higher molecular energy.

What packaging solutions are proposed to prevent photolysis?

Opaque and inert packaging such as amber bottles and aluminium foil blisters help to prevent light from coming into direct contact with the drug, causing degradation.

How can trace metal catalysis be prevented in drug manufacturing?

By adding chelating agents to ‘cut’ off metal compounds. Trace metals can act as catalysts to speed up drug degradation.

• Using chelating agents reduces/minimizes drug degradation.

How is hygroscopicity defined in drug stability?

The absorption of moisture causing a drug to dissolve itself, which is dependent on relative humidity of the environment.

What are the minimum duration requirements for accelerated and long-term stability testing?

Accelerated testing requires a minimum of $6\,\text{months}$, and long-term testing requires a minimum of $12\,\text{months}$.

What stability data is required for Step 4 (Product Registration)?

Stability data for $3\,\text{production batches}$ stored for the stated shelf-life (e.g., $3\,\text{years}$).

Which specific guidelines provide the framework for stability testing?

ICH Stability Testing Guidelines Q1A (R2) 2003.

What are the conditions needed for accelerated testing of 6 months?

• The drug of interest is placed under harsher conditions under a shorter period of time, in order to get results faster compared to non-accelerated test.

What are the conditions needed for long-term stability testing?

• Long-term stability testing involves putting the drug of interest in milder conditions compared to accelerated testing, but over a longer period of time to assess drug degradation and shelf-life.

• Although it produces results at a much slower pace, it gives a more realistic result as drugs in daily life setting will not encounter such harsh environmental conditions, other than certain exceptions.

After HSA approval/authorization, what other processes must be conducted after?

• Marketing and Post-marketing stability and performance has to be observed closely still afterwards, feedback and reports are taken seriously for every single drug, especially new ones

• It helps to verify maintenance of product quality in real-life scenarios/normal consumer usage

• Can be time-consuming and laborious to keep track of results and other side effects, but it is absolutely necessary for ensuring safety and quality of the drug.

When molecules are broken down by certain physical means (e.g. light), what happens and what is the end result?

• when molecules are broken down by light, stored energy within the molecules is released into the surrounding environment.

• this increase in energy can lea to decomposition, conversion of energy to another energy form, energy transfer/retention or emission of light at a new wavelength.