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LC-20-ADI-042 High Performance Liquid Chromatography Online dissolution of Metformin ER tablets using Electrolab Veritas-08 with Shimadzu Nexera FV HPLC Extended release (ER) or sustained release dosage forms are designed to release a drug at predetermined rate in order to maintain a constant drug concentration for a specific period of time with minimum side effects. This can be achieved through variety of formulations. Due to modified dosage forms, dissolution study to assess quality and absorption patterns must be checked over longer durations. This means the dissolution tests are in these cases generally run for more than 16 hours. Needless to say, this presents both technical and administrative challenges. Maintaining complete traceability and avoiding errors are big tasks in hand for lab managers running ER dissolution assays. Under these circumstances, it’s highly desired to have an automated workflow starting from setting up of batch and aliquoting till reporting. Such a set-up will also enable operations without the need of a chemist with complete reliability. Most critical aspect and need of hour, irrespective of formulation type is ensuring compliance. An automated set- up with complete compliance is need of an hour so as to ensure higher productivity and reduced errors with full traceability. KEYWORDS: Nexera FV, Veritas 8, online dissolution, compliance, Metformin dissolution reports. Shimadzu Nexera FV connected to Electrolab dissolution tester, enables automation of the entire dissolution testing process. Since complete workflow from dissolution to reporting is automated and monitored through a single platform of LabSolutions software, entire process has complete traceability and compliance. Sequence of automatic sample aspiration with Nexera FV is as follows: 1. Displace flow vial with sample 2. Aspirate sample from flow vials 3. Analyze directly or fractionate into vials 4. Generate report liquid current Figure 1: Schematic representation of Nexera FV online dissolution set-up ■ Method of analysis Table 1: Dissolution and LC parameters Dissolution parameters Apparatus USP type II(Paddle) Dissolution media Phosphate buffer pH 6.8 Media volume 1000 mL Bath temperature 37 °C Rotational speed 100 rpm Time 720 min Time points 5, 10, 15, 20, 25, 30, 60, 120, 240, 360, 480, 600 and 720 min Key features Compliance ▪ Direct sampling ▪ Audit trail and log for entire process- dissolution test parameters to sample processing and reporting ▪ Complete traceability of dissolution sample ▪ Direct reporting of dissolution result High throughput ▪ Ideal even for profile with 5 min sampling intervals ▪ Walk away operation and analysis ▪ Fast analysis by UHPLC ▪ Reduction of errors- sampling and sample preparation error Ease of use ▪ 3 stage online filtration ▪ Online dilution ▪ Quick reporting ▪ Retain samples in autosampler ■ Introduction Nexera FV provides a means for not only directly sampling the aliquots, but also dilution and HPLC analysis of the samples during the entire test duration for ER tablets resulting in completion of dissolution test and HPLC analysis simultaneously without human intervention. Complete process from dissolution to reporting is automated and monitored through a single platform of LabSolutions Software, thus maintaining compliance. Present work demonstrates the applicability of the Veritas-08 and Nexera FV online dissolution-HPLC system by performing automated dissolution analysis of metformin extended release tablets 1000mg as per USP monograph.
Vessel Quantitation standard Bracketting standard Area RT Area RT 1 425470 4.793 446827 4.794 2 429197 4.792 448733 4.794 3 434201 4.796 448801 4.794 4 433579 4.796 449278 4.796 5 435073 4.795 450121 4.799 6 436181 4.794 448438 4.799 Max. 436181 4.796 450121 4.799 Min. 425470 4.792 446827 4.794 Average 432284 4.794 448700 4.796 Standard deviation 4105.7 0.002 1090.1 0.002 %RSD 0.950 0.037 0.243 0.05 ■ Result and discussion An extended release formulation of metformin was tested for its dissolution profile at time points of 5, 10, 15, 20, 25, 30, 60, 120, 240, 360, 480, 600 and 720 min. Sampling was done in fractionation mode and autosampler dilution feature was used to avoid any manual intervention. Representative HPLC chromatogram are shown in Figure 2. System suitability samples were assessed for percentage deviation of retention time and area, and results were found to be acceptable as shown in Table 2. Dissolution profile was found to be acceptable based on 80% release criteria (as shown in Figure 3). Percentage release value for 6 vessel for all 8 sampling points is tabulated in Table 3. LabSolutions multi data report function was used for auto generation of report and dissolution profile. Not only automation but complete compliance is achieved using Veritas-08 and Nexera FV Table 2: System suitability results Figure 2. Representative chromatogram for Metformin (L) 5 min (R) 240 min Figure 3. Dissolution profile for metformin extended release formulation Table 3: Percentage release value for 6 vessels at different time points Copyright © 2013 SHIMADZU ANALYTICAL (INDIA) PVT. LTD. All rights reserved. No part of this document may be reproduced in any form or by any means without permission in writing from SHIMADZU ANALYTICAL (INDIA) PVT. LTD. Shimadzu Analytical (India) Pvt.Ltd. 1 A/B, Rushabh Chambers, Makwana Road, Marol, Andheri (East), Mumbai- 400059, India. Tel: +91 22 29204741 Fax: +91 22 29205679 www .shimadzu.in LC parameters Column Shiseido C18,4.6mm x150mm,5μm Column temperature 45°C Flow rate 0.75 mL/min Injection volume 2 μL Wavelength 218 nm Detector cell temperature 45 °C Autosampler temperature 4 °C Mobile phase buffer 0.5 g/L sodium heptane sulfonate and 0.5g/L sodium chloride in water. Adjust pH to 3.85 with phosphoric acid. Mobile phase Acetonitrile:buffer (10:90) Online dilution 10 times Standard concentration 100 ppm 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 min -1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0mV Metformin/4.803 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 min -5.0 -2.5 0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5 25.0 27.5 30.0 32.5 35.0 37.5 40.0 42.5 45.0 47.5 50.0mV Metformin/4.815 LC-20-ADI-042 % Release Time (min) 5 10 15 20 25 30 60 120 180 240 360 480 600 720 Vessel No. 1 5.1 7.7 11.9 14.6 18.2 21.9 28.2 41.2 51.3 59.7 67.1 73.8 81.2 81.9 2 4.5 8 11.8 13.2 17.3 20.7 27.5 38.2 51.7 56.2 66.5 73.2 80.7 80.7 3 4.9 8.7 12.1 15.2 16.2 20.5 28.5 41.2 55.5 61.0 70.0 76.4 80.1 80.1 4 4.9 8.8 11.9 14.1 17.1 19.8 29.1 41.9 51.8 59.5 66.7 75.1 82.4 82.4 5 5.0 8.0 12.0 14.3 16.9 22.0 27.1 41.5 52.3 59.0 67.5 76.3 79.6 79.9 6 3.8 7.5 10.2 14.9 18.0 21.6 30.1 41.8 51.4 61.2 67.0 75.9 82.1 82.1 Max. 5.1 8.8 12.1 15.2 18.2 22 30.1 41.9 55.5 61.2 70.0 76.4 82.4 82.4 Min. 3.8 7.5 10.2 13.2 16.2 19.8 27.1 38.2 51.3 56.2 66.5 73.2 79.6 79.9 Average 4.7 8.1 11.7 14.4 17.3 21.1 28.4 41.0 52.3 59.4 67.5 75.1 81.0 81.2 Standard deviation 0.5 0.5 0.7 0.7 0.7 0.9 1.1 1.4 1.6 1.8 1.3 1.3 1.1 1.1 %RSD 10.3 6.4 6.1 4.8 4.2 4.1 3.8 3.3 3.0 3.0 1.9 1.7 1.3 1.3 0 10 20 30 40 50 60 70 80 90 0 100 200 300 400 500 600 700 800 Average % Release Time (in min) 5 min 240 min For Research Use Only. Not for use in diagnostic procedures. Contents and/or instrumentations in this application may not available in some countries under each regulation. Please contact the local representatives in details.
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