Identification of raw materials

Ensuring homogeneous mixing of the components (APIs and excipients) of a pharmaceutical preparation is a crucial prerequisite for obtaining proper solid dosages (tablets and capsules). Pharmaceutical manufacturers invest much time, labor and material resources in this process. Blending is intended to ensure uniform distribution of all components in the end products,so that each dose wiU contain the correct amount of the active ingredient. 

Analyte Pattern recognition method Remarks References 

Raw materials Mahalanobis distance and residual variance Classification models development 24 

Raw materials Correlation coefficient, Mahalanobis distance, residual variance Libraries and sublibraries 63 

Oxytetracycline PCA and SIMCA Sample identity determination before multivariate quantitation 64 

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Raman spectroscopy is emerging as a powerful analytical tool in the pharmaceutical industry, both in PAT and in qualitative and quantitative analyses of pharmaceuticals. Reviews of analyses of pharmaceuticals by Raman spectroscopy have been published.158 159 Applications include identification of raw materials, quantification of APIs in different formulations, polymorphic screening, and support of chemical development process scale-up. Recently published applications of Raman spectroscopy in high-throughput pharmaceutical analyses include determination of APIs in pharmaceutical liquids,160,161 suspensions,162 163 ointments,164 gel and patch formulations,165 and tablets and capsules.166-172... 

Proper identification of raw materials, intermediates, and finished products is necessary to prevent misuse and mix-ups. Labels are controlled and accounted for to prevent mislabeling. If required, packages may be sealed to provide an alert of mishandling or unauthorized tempering. 

Identification Quality Assessment. In a first of its kind paper, Rose in 1982 showed that a number of structurally similar penicillin-type drugs could be identified and determined by NIR. At Sandoz, Ciurczak in 1984 reported using Mahalanobis distance-based algorithms for the identification of raw materials. ° Ciurczak also reported the use of spectral matching (SM) and principle component analysis (PCA) for raw materials and suggested a method for introducing variations into samples for more robust equation development in 1986. NIR has been in use for raw material ID since then in companies worldwide. 

Currently, the primary use of NIR for pharmaceutical analysis is in the identification of raw materials. Some regulatory agencies have mandated that 100% of the materials to be released for use should be verified, rather than the use of traditional statistical sampling, before the materials are mixed and compounded in production. If NIR is utilized to comply with this mandate, a 1997 European Pharmacopoeia monograph, which specifies the minimum standards for an NIR identification method, should be consulted. ... 

The near-IR spectral region has been used for chemical identification as well. Along with being used for analysis of polymorphic forms (43) and identification of raw materials and excipients (44,45), near-IR spectroscopy has also been used to test intact tablets (46). Aldridge et al. (47) have also demonstrated that active and placebo tablets can be identified by near-IR spectroscopy nonde-structively inside blister packs. 

The system should allow the traceability of product upstream and downstream. Identification of raw materials used in the production of processed materials should be traceable through the batch numbering system or any other appropriate system. 

Material analysis identification of raw material shape, sizes, type (cast, bar, etc.), and weight. 

Rodionova et al. used principal component analysis (PCA) and SIMCA to determine the identification of raw materials in their original packaging [29]. Chen et al. [30] discuss the development of a multisite multiinstrument database used for the identification of raw materials. Authors provided insights regarding the validation and routine testing methods. More recently, Wen et al. [31] compared several spectroscopic techniques and determined that NIR was particularly well suited for detecting the presence of adulterants but not their identity. 

D. A. Bums and E. W. Ciurczak, Identification of Raw Materials by NIRA, Handbook of Near-Infrared Analysis, 3rd ed., CRC Press, Boca Raton, FL, 2007. 

The use of modem NIR in the pharmaceutical industry began soon after its use in the food and agricultural industries. Early applications included the measurement of moisture, particle size, the determination of composition, and identification of raw materials. 

Rubinovitz, R., Rapid Identification of Raw Materials with Near-Infrared Spectroscopy, Natural Pharmacy, 6(4), April (2002). 

Identification of raw material, in-process stock and finished products... 

Good manufacturing practices (GMP), established in the cosmetics industry (COLIPA, 1994), involve the control of the contents of the container according to the manufacturer s specifications. NIR is recommended as an analytical technique by Grunewald et al. (1998) for rapid and nondestructive identification of raw materials, product control and end-product analysis. As an example, sodium lauryl ether sulfate and cocobetaine in bubble bath lotion were identified. 

Recent studies of micro ATR have defined the best experimental conditions for establishing optical contact between the ATR crystal and the sample [25]. This experimental approach has been applied to the analysis of the failure surfaces of adhesively bonded joints. ATR-microscopic measurements have been used for direct measurement and identification of raw materials in textiles coated and impregnated substances on paper [26]. An ATR microscopic probe has been developed which allows one to examine the sample optically through the probe in the microscope. The hemispheric ATR crystal is mounted at the focus of the Cassegrain objective, below the secondary mirror. One can position the crystal in contact with the sample, and run the spectra [27]. In the survey mode, visible light at nearly normal incidence is selected to locate the area of measurement. In the contact mode, low incident angle visible is used to detect contact of the sample to the ATR crystal surface. In the measurement mode, the ATR crystal is slid into position and the incident beam is optimized for total internal reflection. In the Spectra Tech version, all of the available crystals, i.e. ZnSe, Diamond, Silicon, and Germanium can be used. However, Ge and Si are opaque and cannot be used in the survey or contact mode. An optical contact sensor can be used. 

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