SPECTROSCOPIC TECHNIQUES

Transmission FT-IR Spectroscopy Applied to the Determination of Hydrocarbon Residues on Pharmaceutical Process Equipment

A N T H O N Y G. S E V E R D I A Sterling Winthrop Pharmaceutical R&D, 9 Great Val- ley Parkway, Malvern, Pennsylvania 19355

Index Headings: Infrared spectroscopy; Hydrocarbon residues; Analyt- ical methods; Spectroscopic techniques.

INTRODUCTION

In the course of operating process equipment in the pharmaceutical industry, it is necessary to assure that all product contact surfaces of process equipment contain a minimum amount of residue. The residue may be another product remaining from a previous operation, an excip- ient, or a "nonformulation" type of material. This report discusses the determination of hydrocarbons, in the form of lubricating greases, on the product contact surface of various tablet presses by use of FT-IR spectroscopy. The FT-IR spectroscopic method provides for both identifi- cation and quantitation of the lubricant and was suggested by an EPA method.

DISCUSSION

During the operation of the presses, various surfaces may come in contact with either feed material (granula- tion) or a finished tablet or caplet. The presence or car- ryover of lubricant by mechanical or physical transport is unacceptable. Even if a food-grade lubricant is being employed, levels of transfer must be such that unaccept- able effects (for example, carryover onto product surfaces) are minimized. Limits for carryover and the relevant for- mulae for calculating such limits have been reported. 2 The actual methodology followed to determine hydro- carbon residues is now described.

Surfaces of machinery were swabbed with Whatman # 1 filter paper wetted with n-hexane (HPLC solvent grade).

Received 11 October 1994; accepted 17 December 1994.

(The filter papers had been rinsed in n-hexane to remove any trace residue, then air dried.) After a swab had cleaned a specified surface area, it was air dried; then any hydro- carbon residue was extracted by sonication of the swab in n-hexane. Next, the swab was removed from the hex- ane extract, and the hexane extract was gently evaporated to dryness.

To the dry residue was added a known volume of CDCl3 (99.6+ atom %D), the mixture was gently swirled, and immediately a solution infrared spectrum was obtained. A Nicolet Magna 550 FT-IR was employed to acquire transmission spectra. A total of 32 scans were taken, each, for sample and background. Spectral resolution was 4 cm -1. The background spectrum was CDCI3 in a cell of equal pathlength. Quantitation of lubricant was obtained by ratioing the absorbance of the sample at ~2930 cm- to that of the absorbance of a solution of lubricant at a known concentration at ~ 2930 cm- 1. The frequency cho- sen was that of the CH2 asymmetrical stretch character- istic of long-chain hydrocarbons. 1 The solvent, CDC13, has a low absorbance in the 3100-2500 cm-1 region. Cell pathlength and extraction volume were chosen to opti- mize absorbance of sample and standard at the analytical frequency, within the ranges of hydrocarbon concentra- tion expected.

The results found, milligrams of hydrocarbon, were related to surface area swabbed. Typical standard and

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FiG. 1. FT-IR spectrum of a 2.43 mg/mL solution of lubricant grease in CDC13. Transmission cell; pathlength of 0.5 mm. The region em- ployed for analysis is shown.

540 Volume 49, Number 4, 1995 0003-7028/95/4904-054052.00/0 APPLIED SPECTROSCOPY © 1995 Society for Applied Spectroscopy

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Fia. 2. FT-IR spectrum of a CDCI3 solution of a swab extract. Con- ditions were the same as for Fig. 1. 0.12 /

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swab extract spectra are shown in Figs. 1 and 2, respec- tively. Lubricant amounts detected varied, but quanti- ration o f as little as 0.2 mg o f lubricant per swab was not atypical. (The organic residue from a "prer insed swab" was de termined as 0.04 mg.) Figure 3 is a calibration curve showing the linear relationship between absorbance and hydrocarbon concentrat ion within the operational range o f the present work.

The FT- IR technique which has been described was used to detect residues f rom a number o f tablet presses. Swab samples were taken after the presses had been cleaned, both before and after a product run. The results obtained f rom the several presses studied indicated that lubricant residue was at milligram to submilligram level per swab for all but the punch elements themselves. Such

Conc., mg/mL

FiG. 3. Graph of absorbance, 2927 cm ~, vs. the concentration of lubricant grease in mg/mL CDCI3. The line had a linear regression coefficient of 0.9999.

a result had been expected prior to the undertaking o f the present work.

1. "Petroleum Hydrocarbons, Total Recoverable, Method 418.1 (Spec- trophotometric, Infrared)", in Methods for ChemicaI Analysis of Wa- ter and Wastes, EPA-600/4-79-020, United States Environmental Protection Agency, Environmental Monitoring and Support Labo- ratory, Office of Research and Development, Cincinnati, OH, Ed. (NTIS, Springfield, Virginia, 1983), 3rd ed., p. 493.

2. G. L. Fourman and M. V. Mullen, Pharmaceutical Technol. 17, 54 (1993).

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