Chemistry Reference
In-Depth Information
as atomic absorption spectroscopy, are also commonly used for other inorganic
impurities.
6.5.8 m
IcrobIAl
l
ImItS
Where needed, pharmacopeial procedures are used to specify parameters such as the
total aerobic microorganism count, the total count of yeast and molds, and the absence
of specific objectionable bacteria. The choice of the type of microbial tests and accep-
tance criteria is based on the nature of the drug substance and method of manufacture.
6.6 specIFIc tests/crIterIA: neW solId
orAl drug products
For some new drug products, additional testing may be needed, depending on the
dosage form. The specific dosage forms highlighted in the guidance include solid
and liquid oral drug products and parenterals. For solid oral drug products, specific
additional tests include dissolution, disintegration, hardness/friability, and unifor-
mity of dosage units.
6.6.1 d
ISSolutIon
Specifications for solid oral dosage forms usually include a test to measure release
of the drug substance from the drug product by dissolution. For immediate release
formulations, single point determinations are commonly used. For modified
release formulations, appropriate test conditions and sampling procedures must
be established. In general, multiple time-point rate release curves are called for
when testing extended or delayed release formulations. In instances where the
rate of release can be demonstrated to significantly affect bioavailability, batch
tests that can discriminate between acceptable and unacceptable bioavailability
are needed. In this instance, in vitro/in vivo correlation may be used to establish
acceptance criteria. In practice, the variability in mean release rate at any given
time point should not exceed a total difference of ±10% of the labeled content of
the drug substance (i.e., a total variability of 20%; a requirement of 50% means a
range from 40% to 60%).
6.6.2 d
ISIntegrAtIon
Disintegration may be substituted for dissolution for rapidly dissolving (dissolu-
tion >80% in 15 min at pH 1.2, 4.0, and 6.8), highly soluble (dose/solubility volume
<250 mL from pH 1.2 to 6.8) new drug products. Disintegration is also appropriate
where a relationship to dissolution has been documented.
6.6.3 h
ArdneSS
/f
rIAbIlIty
Hardness/friability is normally performed as an in-process control (addressed previ-
ously). It is usually only necessary to include these attributes in the specification if
