Chemistry Reference
In-Depth Information
A comparable HPLC separation would take 60 min to perform, not including col-
umn reequilibration. UHPLC accomplishes the same separation in much less time
(4 min) and with better resolution and sensitivity. And because UHPLC uses the same
theories and principles as HPLC, due to the high speed of the UHPLC analyses, meth-
ods can be developed much faster. For more details on UHPLC, see Section 3.3.3.
7.3.2 SIm v
AlIdAtIon
SIMs fall into the quantitative division of Category II (Section 7.1.2); and as such,
all analytical performance parameters must be determined except for the limit of
detection (limit of quantitation would apply instead because SIMs need to be quan-
titative; however, it is commonplace to determine both, as reporting and quanti-
tation levels of impurities can differ). Details of each of the remaining analytical
performance parameters (definitions, measurement, and documentation) have been
summarized previously (see Chapter 4), and it is really not necessary to repeat them
here. However, it should be noted that the hyphenated techniques (e.g., LC/PDA,
LC/MS, and LC/MS/MS) and new technology (e.g., UHPLC) outlined previously
for method development (Chapter 3) can also be used to great advantage in method
validation. For example, specificity (selectivity), while certainly a goal in method
development, must also be demonstrated for proper validation. Therefore, all of
the foregoing discussion relating to specificity (selectivity) in method development
would also apply to validating the method.
7.4 developIng And vAlIdAtIng dIssolutIon procedures
In vitro dissolution performance tests for solid oral dosage forms, such as tablets and
capsules, are used to assess the lot-to-lot quality of a drug product, guide develop-
ment of new formulations, and ensure the product quality and performance after
changes in the manufacturing process, for example, moving to a different site or
scale-up. As with any performance test performed in a regulated environment, the
dissolution procedure must be properly developed and validated. Dissolution testing
is an example of a Category III test (Table 7.1, Section 7.1.3).
The dissolution performance test is a required test for all solid oral dosage forms
for product release testing. It is also commonly used as a predictor of a drug prod-
uct's in vivo performance. To help satisfy dissolution requirements, the USP provides
information by way of a general chapter on dissolution, as well as related chapters on
disintegration and drug release [25-28]. These USP chapters also provide guidelines
on development and validation of dissolution procedures, and should be consulted
for additional details.
In vitro dissolution data, together with bioavailability, and chemistry, manufac-
turing and control (CMC) data, is a critical component of any new drug application
submitted to the FDA. A dissolution test is really a simple concept; a tablet or cap-
sule is placed in a known volume of media, and as it dissolves the resulting solution
is sampled over time, and assayed (often by HPLC, but also by spectrophotometry)
for the level of API present. However, the design, development, and the validation
of the procedure can be quite involved, especially when one considers that not only
