Follow these instructions to conduct stability studies effectively on various pharmaceutical dosage forms:
General Considerations:
For each dosage form:
- Evaluate appearance, assay, and degradation products.
- Limit degradation product testing for generic products to compendial requirements.
Note:
- The listed tests are not exhaustive.
- Not every test needs to be included in the stability protocol.
- Consider safety when performing tests, only conducting necessary assessments.
- Not every test needs to be performed at each time point.
- Consider storage orientation changes in the protocol.
Dosage Forms Specific Tests:
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Tablets:
Evaluate appearance, odour, colour, assay, degradation products, dissolution, moisture, and hardness/friability.
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Capsules:
For hard gelatin capsules, assess appearance (including brittleness), colour, odour of content, assay, degradation products, dissolution, moisture, and microbial content.
For soft gelatin capsules, assess appearance, colour, odour of content, assay, degradation products, dissolution, microbial content, pH, leakage, pellicle formation, and fill medium examination.
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Emulsions:
An evaluation should include appearance (including phase separation), colour, odour, assay, degradation products, pH, viscosity, microbial limits, preservative content, and mean size and distribution of dispersed globules.
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Oral Solutions and Suspensions:
The evaluation should include appearance (including formation of precipitate, clarity for solutions), colour, odour, assay, degradation products, pH, viscosity, preservative content and microbial limits.
Additionally for suspensions, redispersibility, rheological properties and mean size and distribution of particles should be considered. After storage, sample of suspensions should be prepared for assay according to the recommended labeling (e.g. shake well before using).
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Oral Powders for Reconstitution:
Oral powders should be evaluated for appearance, colour, odour, assay, degradation products, moisture and reconstitution time.
Reconstituted products (solutions and suspensions) should be evaluated as described in Oral Solutions and Suspensions above, after preparation according to the recommended labeling, through the maximum intended use period.
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Metered-dose Inhalations and Nasal Aerosols:
Metered-dose inhalations and nasal aerosols should be evaluated for appearance (including content, container, valve, and its components), colour, taste, assay, degradation products, assay for co-solvent (if applicable), dose content uniformity, labeled number of medication actuations per container meeting dose content uniformity, aerodynamic particle size distribution, microscopic evaluation, water content, leak rate, microbial limits, valve delivery (shot weight) and extractables/leachables from plastic and elastomeric components. Samples should be stored in upright and inverted/on-the-side orientations.
For suspension-type aerosols, the appearance of the valve components and container’s contents should be evaluated microscopically for large particles and changes in morphology of the drug surface particles, extent of agglomerates, crystal growth, as well as foreign particulate matter.
These particles lead to clogged valves or non-reproducible delivery of a dose. Corrosion of the inside of the container or deterioration of the gaskets may adversely affect the performance of the drug product.
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Nasal Sprays: Solutions and Suspensions:
The stability evaluation of nasal solutions and suspensions equipped with a metering pump should include appearance, colour, clarity for solution, assay, degradation products, preservative and antioxidant content, microbial limits, pH, particulate matter, unit spray medication content uniformity, number of actuations meeting unit spray content uniformity per container, droplet and/or particle size distribution, weight loss, pump delivery, microscopic evaluation (for suspensions), foreign particulate matter and extractable/bleachable from plastic and elastomeric components of the container, closure and pump.
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Topical, Ophthalmic and Otic Preparations:
Included in this broad category are ointments, creams, lotions, paste, gel, solutions and non-metered aerosols for application to the skin. Topical preparations should be evaluated for appearance, clarity, colour, homogenity, odour, pH, resuspendability (for lotions), consistency, viscosity, particle size distribution (for suspensions, when feasible), assay, degradation products, preservative and antioxidant content (if present), microbial limits/sterility and weight loss (when appropriate).
Evaluation of ophthalmic or otic products (e.g., creams, ointments, solutions, and suspensions) should include the following additional attributes: sterility, particulate matter, and extractable.
Evaluation of non-metered topical aerosols should include: appearance, assay, degradation products, pressure, weight loss, net weight dispensed, delivery rate, microbial limits, spray pattern, water content, and particle size distribution (for suspensions).
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Suppositories:
Suppositories should be evaluated for appearance, colour, assay, degradation products, particle size, softening range, dissolution (at 37oC) and microbial limits.
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Small Volume Parenterals (SVPs):
SVPs include a wide range of injection products such as Drug Injection, Drug for Injection, Drug Injectable Suspension, Drug for Injectable Suspension, and Drug Injectable Emulsion. Evaluation of Drug Injection products should include appearance, clarity, colour, assay, preservative content (if present), degradation products, particulate matter, pH, sterility and pyrogen/endotoxin.
The stability assessments for Drug Injectable Suspension and Drug for Injectable Suspension products should encompass particle size distribution, redispersibility, and rheological properties, along with the previously mentioned parameters for Drug Injection and Drug for Injection products.
For Drug Injectable Emulsion products, in addition to the parameters outlined for Drug Injection, the stability studies should also cover phase separation, viscosity, and the mean size and distribution of dispersed phase globules.
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Large Volume Parenterals (LVPs):
Evaluation of LVPs should include appearance, colour, assay, preservative content (if present), degradation products, particulate matter, pH, sterility, pyrogen/endotoxin, clarity and volume.
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Drug Admixture:
For any drug product or diluents that is intended for use as an additive to another drug product, the potential for incompatibility exists. In such cases, the drug product labeled to be administered by addition to another drug product (e.g. parenterals, inhalation solutions), should be evaluated for stability and compatibility in admixture with the other drug products or with diluents both in upright and in inverted/on-the side orientations, if warranted.
A stability protocol should provide for appropriate tests to be conducted at 0-,6- to 8- and 24-hour time points, or as appropriate over the intended use period at the recommended storage/use temperature(s). Tests should include appearance, colour, clarity, assay, degradation products, pH, particulate matter, interaction with the container/closure/device and sterility. Appropriate supporting data may be provided in lieu of an evaluation of photo degradation.
- Transdermal Patches:
Stability studies for devices applied directly to the skin for the purpose of continuously infusing a drug substance into the dermis through the epidermis should be examined for appearance, assay, degradation products, in-vitro release rates, leakage, microbial limits/sterility, peel and adhesive forces, and the drug release rate.
- Freeze-dried Products:
Appearance of both freeze-dried and its reconstituted product, assay, degradation products, pH, water content and rate of solution.