Excipients solvent extraction methods

Solvent extraction procedures provide simple methods for separating the analyte from excipients in formulations. The analytical method applied to the isolated analyte can be for example either gravimetric, volumetric, spectrophotometric or chromatographic. In most cases in the pharmaceutical industry chromatographic methods are preferred. The extraction method adopted is governed by the need to remove excipients and by the properties of the analyte. 

Besada et al. [13] described spectrophotometric methods for determination of penicillamine in pure and dosage forms. Penicillamine was measured spectrophoto-metrically in 0.1 M HC1 (at 195 nm) or in 0.1 M NaOH (at 238 nm). Both methods gave recoveries of 100% with good precision. For determination of the drug in tablets, in the presence of excipients, ground samples were extracted with each of these solvents and the difference in absorbance at 238 nm between the two solutions were measured. The recovery of the drug from commercial tablets was 99.8%, with a coefficient of variation of 0.38%. The three methods were suitable for 4—130 ppm of the drug. 

To demonstrate that no excipients interfere with the drug substance, a TLC plate is prepared like the one on the left in Figure 10, where the drug substance is extracted from its formulation, compared with that of a placebo (a synthetic blend is prepared according to the formulation order if no placebo is available at the time of method development and validation). The in-going bulk lot of drug substance is weighed at the proper concentration, diluted in the extraction solvent, and applied to the same TLC plate for analyses. 

Many of the techniques described above, excipient compatibility, blend uniformity by HPLC dissolution, and content uniformity/assay by HPLC can be effectively automated by robotic sample preparation. Each of these techniques requires that the sample under study be dissolved in an appropriate solvent and fully extracted from any excipients. There are a number of commercially available products that have proven to be effective and robust in this sample preparation role. This robotic process can reduce both the analyst hours required to prepare a number of samples, and turnaround time on the sample analysis, since the robotic systems will operate unattended over night and on weekends. There is of course a cost to pay for laboratory automation. There is a significant capital cost, and then an ongoing maintenance cost for the continued operation of the system. Also it is critical that a specialist be available in-house to care for the system, develop the methods, and troubleshoot any issues with the system. The cost of the system and specialist must be weighed against the advantages of speed and lab capacity enhancement realized with a successful automation implementation. 

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