Pharmaceutical Shelf Life and Stability

Shelf Life

• Shelf life is the time period during which a drug product is expected to remain within approved specifications for use, provided it is stored under the conditions defined on the container label.
• Expiration date is the date placed on the container label of a drug product designating the date after which a batch of the product is not expected to remain with approved specifications, if stored under defined conditions, and after which it must not be used.
• Half-Life: the period of time required for a drug to decompose to one-half of the original concentration
• Manufacturers determine k, because of its relationship to shelf life
• Drug in solution and suspensions decompose at different rates
• Pharmacists must be able to recognize drugs with stability problems and have strategies to prevent those problems.
• To overcome chemical instability, changes can be made to formulation, storage conditions, and packaging.
• Drug stability is closely linked to chemical kinetics and rates of degradation.

Rate Constants and Reaction Rates

• Specific rate constant (k) is the constant in the rate law associated with an elementary reaction.
• Any changes in reaction conditions such as temperature, solvent will lead to a different value for the specific rate constant.
• Variations in the specific rate constant are of great physical significance because a change in this constant represents a change at the molecular level as a result of a variation in the reaction conditions.
• Rate constants derived from reactions consisting of a number of steps of different molecularity are functions of the specific rate constants for the various steps.
• Variations in an overall rate constant can be used to provide useful information about a reaction, but changes can affect multiple specific rate constants.

Molecularity

• A reaction whose overall order is measured can be considered to occur through several steps or elementary reactions.
• Each of the elementary reactions has a stoichiometry giving the number of molecules taking part in that step.
• The order of an elementary reaction gives the number of molecules coming together to react in the step; this is the molecularity of the elementary reaction.
• Solution reactions, especially in aqueous solutions, generally involve contributions to their reaction mechanisms from solvent molecules, which require specialized techniques to quantify and to understand.
• Reactions can be unimolecular, bimolecular, or termolecular (rare).
• Complex reactions proceed through more than one step.

Molecularity

• Molecularity is the number of molecules, atoms, or ions coming together to react in an elementary reaction.
• Unimolecular reactions: A single molecule produces the product.
• Bimolecular reactions: Two molecules produce the product.

Rates of Drug Degradation: Pseudofirst (Apparent) Order

• Most drugs decompose by reacting with other species.
• A simplified equation used to describe the reaction rate as pseudofirst order is used.
• "Apparent" or "pseudo"-order describes a situation where all but one of the reactants is present in large excess, or do not affect the overall reaction and can be held constant.

Learning Outcomes

• Calculate shelf life with changes in temperature.
• Describe environmental factors that affect shelf life.
• List and evaluate the approaches used to prevent drug stability problems.

Factors that Affect Shelf Life - Temperature

• Rates of reaction are affected by temperature.
• The reaction rate is expected to increase with increasing temperature based on collision theory.
• Frequency factor (Arrhenius factor): a constant indicating how many collisions have the correct orientation to lead to products.

Packaging

• Packaging can be chosen to protect from oxygen, water vapor, and light.
• Permeability: the ability of volatile substances to move through packaging material.
• Leaching: loss of materials from the packaging into the drug solution.
• Adsorption: Active or inactive components of drug solution adhere to the surface of packaging materials, which reduces the concentration in solution.

Packaging Considerations

• Type I glass leaches low levels of metal oxides into water and drug solutions.
• Other glass types have higher levels of leaching and should be used with caution, especially for drug solutions with pH greater than 7.
• Plastics have a number of additives that are potential leachables into drug solutions.
• Rubber materials in stoppers and syringe plungers can leach metals, 2-mercaptobenzothiazole, and nitrosamines.

This quiz covers essential concepts related to the shelf life and stability of pharmaceutical products. It includes definitions of shelf life, expiration dates, and half-life, as well as factors affecting drug stability. Insight into the role of pharmacists in managing drug stability and the chemical kinetics involved is also discussed.