Corresponding authentic product (except Cialis 50 mg), along with generic amlodipine besylate 10 mg tablets, were purchased
from McKesson, a major distributor in the US.
Instrumentation.
With some exceptions, NIR spectra were collected using the methods of Tatavarti et al. (9). The authors used an RCA XDS NIR
spectrometer (Foss NIRSystems, Columbia, MD) to collect the spectra. Instrument operation and data analysis were performed
using Foss's Vision 3.2 software. The data-collection method was set to full range (400–2500 nm). Samples and references were
scanned in diffuse-reflectance mode an average of 32 times at 0.5-nm intervals. In addition, NIR spectra were collected using
a PHAZIR-Rx instrument (Polychromix, Wilmington, MA).
NIR spectra comparison.
The authors compared the NIR spectrum of each suspected counterfeit product to that of the authentic product using the ρm criterion expressed in the following equation (10, 11):
where R
t is the absorbance of the reference product at wavelength t,
T
t is the absorbance of the test product at wavelength t, and RATIO
t
is the larger of either R
t ÷ T
t or T
t ÷
R
t. Previously, ρm has been used to compare test and reference profiles (e.g., plasma profiles and dissolution profiles) and assess profile
similarity. ρm is weighed by the sum of R
t
and T
t. This weighting factor places more emphasis on the wavelengths with higher absorbtivities. The unweighted criterion is:
Spectra were also compared by the following Deltaa metric (10, 11):
in which δa is based upon the absolute difference between two spectra and considers the relative size of the profiles. For profiles that
are not identical, 0 ≤ δa. In equation 3, δa is weighed by R
t + T
t. The unweighted criterion is:
Other quality tests.
As discussed below, a simple visual inspection of test Cialis 50 mg resulted in the conclusion that it was counterfeit, and
disintegration testing was performed using the US Pharmacopeia method. Disintegration was also conducted on the reference Cialis 20 mg for comparison purposes because authentic Cialis
is not available in 50-mg strength.
Figure 1. Test Cialis 50 mg package. The plastic container appeared to be of low quality and failed to denote tablet quantity,
manufacturer, and distributor. The packaging included a "Lilly" hologram and a misspelled "Lieel icos" marking.
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In addition, when an authentic active pharmaceutical ingredient (API) was available, thin-layer chromatography (TLC) was conducted
on the test and reference products. TLC was performed on amlodipine besylate, sildenafil citrate, and terbinafine hydrochloride
products. Tablets were crushed and subjected to TLC in parallel with the authentic APIs. A 0.3mg/mL solution of drug in methanol
was prepared for amlodipine besylate products and API and run on a TLC plate using a mixture of 2-butanone, water, and glacial
acetic acid in a ratio of 50:25:25 as the mobile phase. For the sildenafil citrate products and API, a 1mg/mL solution of
drug in methanol was prepared and run on a TLC plate using the same mobile phase. Terbinafine hydrochloride products and API
were evaluated using the same method as that for sildenafil citrate. Plates were inspected under ultraviolet light at 254
nm.
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