| potency/assay of active ingredient |
The quantity of
active pharmaceutical ingredient and possibly
key excipients need to be determined. For nanoemulsions that may imply
API content determination in both oil and water phases as well as
the use and validation of advanced extraction protocols to assess
the API content in the oil phase. The acceptable content of an API
can be specified in the compendial monograph of the formulation (if
available) or in general it is kept as 95% to 105% of declared content
for initial analysis and 90% to 110% for shelf life stability analysis. |
| impurities |
Qualitative and quantitative
analysis of degradation products
according to ICH guidelines. Impurity profile analysis using high-sensitivity
analytical methods (e.g., mass spectrometry) is essential to determine
the capability to detect a wide range of degradation products which
may be generated across different stages of manufacturing (e.g., high-pressure
processing or sterilization) during standard quality control process. |
| interactions |
Determination of the
interactions between the API and the container
and critical excipients (e.g., preservatives, viscosity modifiers,
antioxidants). |
| appearance (clarity, color,
odor and consistency) |
Discriminate a potential destabilization
of the emulsions via
creaming, coalescence, Ostwald ripening, and phase separation, changes
caused by microorganisms or decomposition of nanoemulsion components
(API or excipients). |
| particulates |
The test determines the number of solid particles (in sizes
above 10, 25, and 50 μm) per mL of the formulation. In case
of ophthalmic nanoemulsions determination of this parameter should
be possible with microscopic particle count test as light obscuration
particle count test may be challenging due to colloidal nature of
the formulation. |
| uniformity of dosage unit |
The drug content delivered in each drop should be between 85%
and 115% of the average drop content as determined using suitable,
sensitive and validated method. Formulations that have large PDI and/or
colloidal stability issues may not comply with this test as oil phase
content may differ between droplets. |
| withdrawal
content |
The content withdrawn from the container must
be not less than
the label claim of the container. The tested product needs to comply
with this requirement during the whole shelf life i.e. the content
withdrawn at time zero needs to be equal the content withdrawn at
the end of the shelf life of the product. |
| package integrity |
Usually, visual appearance and function. |
| sterility |
In compliance with pharmacopeial
requirements. |
| preservative efficacy |
Determines the level of antimicrobial activity of a product
and can be related with the content of preservative in the formulation.
The test enables to evaluate how well a product withstands microbial
contamination during storage and use (this can be evaluated via in-use
testing for multidose products). |
| stability
studies |
The stability program should be designed in
accordance with
ICH guidelines and in case of novel nanoemulsion based formulations
should be discussed with and accepted by the regulatory body prior
initiating to comply with the specific requirements. |
