Coated Tablet (Drug B)

Let’s now turn our attention to a different dosage form, applying some of the
strategies developed during the examination of drug A. Again we want to identify
the process steps that are responsible for distributing the active ingredient
as well as the tests that measure the effectiveness of those actions. Drug B is a
sugar-coated tablet prepared in the traditional manner; that is, layers are slowly
built up around a core by applying a coat of shellac and then subcoating, gross-
Copyright © 2003 Marcel Dekker, Inc.
ing, and smoothing coats until specifications are met at each stage. In the case
of drug B, the core contains two active ingredients. The coating, on the other
hand, has no medicinal value and is intended solely to enhance the aesthetic
appearance of the product. The manufacturing process is shown in Figure 6.
Table 3 summarizes the selected critical steps for the manufacture of the
core tablet of drug B. The core is prepared by dry-blending the first active
ingredient (i.e., B1) with several excipients. Blend time is of interest for its
impact on the distribution of the therapeutic agent. The premix just prepared is
granulated using an alcohol-binder solution. The process directions allow the
operator some latitude in using additional alcohol to ensure that the batch is
uniformly wet. It will be necessary to know whether or not additional alcohol
is routinely required, and if so, how much is used. Besides measuring operator
technique, the wetting step affects particle size distribution. The oven tray dryer
is identified for drying the wet mix. Granulation drying time is of interest, because
loss on drying is not measured. Once dry, the granulation is milled using
a specified screen size and machine setting. Alternate equipment is not provided
for in the aforementioned steps.
The powder produced in the prior operation is combined with the second
active ingredient (B2), as well as several other excipients in a twin-shell blender
and mixed for several min. For reasons previously discussed, mix time is of
interest, and thus it is listed as a critical process step.
The blend of the two active ingredients (B1 and B2) is slugged and then
the slugs are oscillated. Slugger model and tooling are listed in the batch instructions.
The thickness of the slug is specified, but no information is recorded on
the slugging operation, as control of this procedure is left to the experience of
the press operator. The batch record permits the use of only one screen size.
Since all of the batches have been made in the same manner, this important
process step will not be included as one to be studied.
Next, lubricant and oscillated granulation are blended for several min. The
elapsed mixing time is of interest because of its impact on drug distribution and
the effect of the lubricant on dissolution. During compression, 1000 randomly
selected cores are accumulated for use by quality control.
The ATW, hardness, and disintegration time are determined by the press
operator during compression. As in the case of drug A, we will not rely on these
results for our study, but rather on the test data from quality control.
Following approval of the bulk cores by quality control, they are shellaccoated.
According to the manufacturing directions, one or two coats may be
applied based on the process operator’s judgment. A third coat is permissible
but only in response to directions from the supervisor. In any event, the actual
number of coats applied is recorded in the batch record. Because of its potential
impact on drug availability,Once the shellacking stage has been completed, the cores are built up
through a series of coating operations. The number of applications of coating
solution, the volume of coating solution applied, and the coating environment
can influence product performance and therefore need to be studied.
The quality control tests selected after review of in-process and finishedproduct
specifications are listed in Table 3. The rationale for selection has been
addressed in general terms during the review for drug A. These quality control
tests, while informative, provide no insight into how the shellac coating will
behave a number of years from now. For some perspective, we can examine the
stability profile of commercial batches placed into the stability program. Of
course, the batches considered would have been made by the same process as
the one being validated. Particular attention should be paid to disintegration and
dissolution results.