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The effect of grinding on the pharmaceutical properties of matrix tablets consisting of ground glutinous rice starch (GRS) and theophylline (TH) was predicted by near infrared (NIR) spectroscopy. Ground GRS samples were prepared by grinding GRS in a planetary ball mill for 0-120 min, measured by X-ray diffractometry (XRD) and NIR, and then evaluated for crystallinity (%XRD) based on XRD profiles. Tablets containing TH (5 w/w%), ground GRS (94 w/w%), and magnesium stearate (1 w/w%) were formed by compression. Gel-forming and drug-release processes of the tablets were measured using a dissolution instrument with X-ray computed tomography (XCT). Swelling ratio (SWE) and mean drug-release time (MDT) were evaluated based on XCT and drug-release profiles, respectively. Calibration models for predicting percent %XRD, MDT, and SWE were constructed based on the NIR of ground GRS using partial least-squares. The results indicated the possibility of controlling the pharmaceutical properties of matrix tablets by altering the pre-gelatinization of GRS based on changes in their NIR spectra during the milling process.

The objective of this work is to demonstrate the potential of near-infrared spectroscopy for common screening of falsified medicines in the field by means of a device-independent universal discrimination approach. In order to provide a useful discrimination tool to protect people from low-quality medical products, not only is a low-cost and portable screening device necessary, but a reference library is also essential. The authors believe that a device-dependent reference library inhibits near-infrared spectroscopy from becoming a popular screening tool. In this study, to develop a device-independent method, discrimination performance is evaluated using different devices for training and testing. The training data sets for the reference library were prepared using a bench-top Fourier transform near-infrared spectrophotometer, and predictive discrimination was performed using the spectral data by a low-cost and portable wavelength dispersive near-infrared spectrophotometer. A near-infrared spectrum-based support vector machine was used for these purposes, but the screening resulted in low accuracy thought to be caused by the intrinsically device-dependent features of the spectra data. Thus, principal component analysis was performed to collect the proper components to discriminate low-quality products from standard products. The principal component score-based support vector machine was able to produce highly accurate results, identifying falsified products with no false positive cases.

The manufacturing of solid pharmaceutical dosage forms composed of cocrystals requires numerous processes during which there is risk of dissociation into parent molecules. Resonant acoustic wet granulation (RAG) was devised in an effort to complete theophylline-citric acid (THPCIT) cocrystal formation during the granulation process, thereby reducing the number of operations. In addition, the influence of granulation liquid was investigated. A mixture of anhydrous THP (drug), anhydrous CIT (coformer), and hydroxypropyl cellulose (granulating agent) was processed by RAG with water or ethanol as a granulation liquid. The purposes were to (i) form granules using RAG as a breakthrough method; (ii) accomplish the cocrystallization during the integrated unit operation; and (iii) characterize the final solid product (i.e., tablet). The RAG procedure achieved complete cocrystal formation (>99%) and adequately sized granules (d50: >250 mu m). The granulation using water (GW) facilitated formation of cocrystal hydrate which were then transformed into anhydrous cocrystal after drying, while the granulation using ethanol (GE) resulted in the formation of anhydrous cocrystal before and after drying. The dissolution of the highly dense GW tablet, which was compressed from granules including fine powder due to the dehydration, was slower than that of the GE tablet.

Cocrystallisation can enhance the solubility and bioavailability of active pharmaceutical ingredients (APIs); this method may be applied to improve the availability of materials that were previously considered unsuitable. Terahertz (THz) spectroscopy provides clear, substance-specific fingerprint spectra; the transparency of the THz wave allows us to probe inside a sample to identify medicinal materials. In this study, THz and infrared (IR) spectroscopy were used to characterise cocrystallisation in solid-phase reactions between ibuprofen and nicotinamide. Multivariate curve resolution with alternating least squares (MCR-ALS) was applied to both time-dependent THz and IR spectra to identify the intermolecular interactions between these cocrystallising species. The analytical results revealed cocrystal formation through a two-step reaction, in which the steps were dominated by thermal energy and water vapour, respectively. We infer that the presence of water molecules significantly lowered the activation energy of cocrystal formation.