The determination of drug tablet
concentration in pharmaceuticalapplications for drug developmentusing the Agilent Cary 60 UV-Vis withfiber optics
Application Note
PharmaAuthorFyfe, DJFyfe Science, West Lakes
Shore, SA 5020, Australia

Note: All of this work was conducted under controlled conditions in a GMP
laboratory within a leading global pharmaceutical manufacturing company.

SummaryThe Agilent Cary 60 UV-Vis spectrophotometer is the new, improved
successor to the award-winning Cary 50. This instrument platform is used ina plethora of applications, including the online dissolution and analysis ofpharmaceutical dosage forms. This document highlights some key benefitsof using the Cary 60 in pharmaceutical applications for drug development
and production in terms of time and cost savings. Specifically, the approachdescribed in this application note may be of significant benefit forpharmaceutical applications where an in situ measurement system, withessentially real-time results could improve productivity and dissolution
profile information.

Introduction
In the pharmaceutical industry, dissolution is an essential tool to determine
the biopharmaceutical quality of solid dosage forms. Essentially, the processinvolves placing the dosage form (i.e., tablets or capsules) in a set of vessels
and agitation components contained within the dissolution apparatus. This
simulates conditions within the gastro-intestinal tract and, as samples arepulled at specific timepoints, the charting of the release of the active
pharmaceutical ingredient (API) from the dosage form is determined by
UV-Vis spectroscopic measurement.
.

In this short review, the benefits that taking in situ
measurements using fiber optics can have for drug
development are explored and potential cost savings
are discussed. In this instance, concentration
measurements of manufactured tablets of anti-malarial
API were taken. This antimalarial compound belongs tothe chemical class of naphthalenes.

Apparatus and materials
Part Number

Description

G6860AA

Cary 60 UV-VIS Spectrophotometer, PC & Software

7910029900

Torlon fiber optic probe

G6866A

Torlon fiber optic probe coupler
Figure 1. Concentration curve for anti-malarial API standards. Calibration
equation: Abs = 0.00688*Conc -0.01056; correlation coefficient= 0.99976.
The dissolution bath was used to facilitate the dissolution to completion, andthe sample was analysed for total dissolved active ingredient after time, Theconcentration measurement of the unknown sample was made at the end of
the dissolution reaction.

Methods and results
Methods were adapted in-house from those describedin British Pharmacopoeia 20111.

Analysis

The Cary 60 instrument was fitted with the fiber optics
coupler and Torlon probe. A blank reading was takenusing 10 mL of isopropanol. Six standard solutions ofanti-malarial API were prepared from zero to 300
mg/mL in isopropanol. Using the Concentration modulein the WinUV software, the standards were sequentiallyread using the fiber optic probe, resulting in a linear
concentration curve as shown in Figure 1. Finally, theconcentration of the anti-malarial API sample in thedissolution bath was determined using the WinUV
software, as shown in report in Figure 2. The WinUV
software contained the 21 CFR part 11 module thatassists with meeting regulatory requirements.

Collection time

3/1/2011 4:00:04 PM

SampleConcentration mg/L

Readings (Abs)

Original anti-malarial API

282.3

1.9312

Duplicate

280.7

1.9200

Triplicate

281.2

1.9238Mean281.4

1.9250

SD =0.0057; %RSD = 0.29583
Figure 2. Concentration curve parameters transcribed directly from theWinUV Conc software for the concentration curve shown in Figure 1. Data
show three independent replicates of an unknown sample of anti-malarial
API following being analyzed for total dissolved active ingredient in anAgilent dissolution bath. The data demonstrates the excellent reproducibilityof the Cary 60 fiber optics instrument platform,

2

Discussion

As evidenced in the data presented in thisdocument, this in situ approach may be ofsignificant fiscal benefit to pharmaceuticalorganizations where a comparatively low number ofsamples are analyzed that do not perhaps justify
purchase and validation of fully automatedsystems. For those applications that require thehandling of larger numbers of samples, Agilent
manufactures an automated fiber optic dissolution
system. This is an extension of the application
discussed in this document and provides users withthe options for not just increased sample
throughput, but also the opportunity to takemeasurements unattended over the course ofanalyses.

Data given in Figures 1 and 2 demonstrate that theperformance of the Cary 60 instrument fitted with fiber
optics was almost perfectly linear (correlation
coefficient = 0.99976) over the absorbance range 0–2
Absorbance units. Moreover, results also showed
excellent reproducibility in determining theconcentration of the three unknown anti-malarial API
samples. This level of performance is critical inpharmaceutical applications such as this, since the data
is ultimately used to determine the precise
concentration of active drug in manufactured tablets.

Conclusions
1. The instrument platform can save time bystreamlining dissolution processes in drug
development by virtue of fiber optics. This permits
sample measurement in situ and alleviates theneed for external UV-Vis analysis away from thedissolution work station, with no compromise in
the quality of data generated. Because the sample
is read in situ, the sampling time points can befaster than can be achieved with conventional
sample transfer systems.

2. Versatile, 21 CFR part 11 capable software assistsin compliance with regulatory requirements at all
times for pharmaceutical manufacture.
1 British Pharmacopoeia 2011 online; British

Pharmacopoeia Volume III; Formulated Preparations:
Specific Monographs.

3www.agilent.com/chem© Agilent Technologies, Inc., 2011
Published May 1, 2011
Publication Number 5990-7945EN