Pharmaceutics · Short notes

Packaging and Stability: Short Notes & Cheat Sheet

Degradation pathways, reaction kinetics, shelf life, ICH stability conditions and packaging materials.

Short notes

Read these before you attempt the topic's MCQs.

ICH stability storage conditions

Hot, humid countries such as Pakistan need data at 30 °C and high humidity; accelerated studies at 40 °C/75% RH predict shelf life sooner.

How drugs degrade

Hydrolysis is the most common pathway, and affects esters and amides (aspirin, procaine, penicillins). Control it by removing water and choosing the pH of maximum stability.
Oxidation affects phenols, catechols and thiols (adrenaline, ascorbic acid). Prevent it with antioxidants, chelating agents (EDTA) and nitrogen flushing.
Photolysis affects light-sensitive drugs (nifedipine, riboflavin, nitroprusside). Use amber glass or opaque packs.
Physical instability includes polymorphic change, caking, cracking of emulsions and loss of volatile ingredients.

Kinetics and shelf life

Zero-order: the rate is constant and independent of concentration (e.g. suspensions, where only dissolved drug degrades). t½ = C₀/2k.
First-order: the rate is proportional to concentration (most solutions). t½ = 0.693/k and t90 = 0.105/k.
Shelf life (t90) is the time for the drug to fall to 90% of its labelled content.
Accelerated stability testing uses high temperature and the Arrhenius equation to predict shelf life at room temperature.
A rough rule is that the reaction rate doubles or triples for every 10 °C rise in temperature.

ICH stability conditions

Long-term testing: 25 °C/60% RH for climatic zones I–II, and 30 °C/65% RH or 30 °C/75% RH for hot and humid zones. Pakistan falls in zone IVa/IVb conditions.
Accelerated testing: 40 °C/75% RH for 6 months.
Intermediate testing: 30 °C/65% RH.
Refrigerated products are stored at 2–8 °C.

Packaging

Glass types: Type I (borosilicate; for all parenterals), Type II (treated soda-lime; for acidic and neutral aqueous parenterals), Type III (soda-lime; for dry powders and non-aqueous products), and NP (non-parenteral; general use).
Plastics (PVC, PE, PP, PET) are light but can let moisture through, leach components or adsorb drugs (e.g. nitroglycerin and diazepam onto PVC).
Blister packs protect individual doses. Aluminium–aluminium blisters give the best moisture barrier.
Child-resistant closures and tamper-evident seals are important safety features.

Cheat sheet

High-yield facts in one place. Cover the right-hand column and test yourself.

Kinetics formulas

Order	Half-life · shelf life
Zero-order	t½ = C₀/2k · t90 = 0.1 C₀/k
First-order	t½ = 0.693/k · t90 = 0.105/k
Arrhenius	log k vs 1/T is a straight line

Glass types

Type	Use
Type I (borosilicate)	All parenterals, including alkaline
Type II (treated soda-lime)	Acidic and neutral aqueous parenterals
Type III (soda-lime)	Dry powders, non-aqueous parenterals
NP (non-parenteral)	Oral and topical products

Degradation → prevention

Pathway	Prevent with
Hydrolysis	Dry forms, optimal pH, avoid water
Oxidation	Antioxidants, EDTA, nitrogen, amber glass
Photolysis	Amber glass, opaque packaging
Moisture uptake	Desiccants, Alu–Alu blisters

Memory aids

t90 = 0.105/k: For first-order reactions the shelf life is 0.105 divided by the rate constant.
40/75 for 6: Accelerated stability: 40 °C, 75% RH, for 6 months.

Exam traps

For a suspension, degradation often follows apparent zero-order kinetics because the dissolved drug is kept constant by the solid reservoir.
Type I glass is borosilicate; Type III is plain soda-lime.
Nitroglycerin is lost by adsorption onto PVC tubing and bags.
Shelf life is based on 90% of labelled content, not 50%.

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