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.

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 μm). 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.

A continuous-spray granulator (CTS-SGR) is a one-step granulation technology capable of using solutions or suspensions. The present research objectives were, (1) to reduce the manufacturing operations for solid dosage formulations, (2) to make amorphous solid dispersion (ASD) granules without pre-preparation of amorphous solids of active pharmaceutical ingredients (API), and (3) to characterize the obtained SGR granules by comprehensive pharmaceutical analysis. Rebamipide (RBM), a biopharmaceutical classification system class IV drug, that has low solubility or permeability in the stomach, was selected as a model compound. Five kind of granules with different concentrations of polyvinylpyrrolidone/vinyl acetate copolymer (PVP-VA) were prepared using a one-step SGR process. All of the SGR granules could be produced in amorphous or ASD form and their thermodynamic stability was very high because of high glass transition temperatures (>178 °C). They were unstable in 20 °C/75%RH; however, their stability was improved according to the proportion of polymer. The carboxy group of RBM was ionized in the granules and interactions appeared between RBM and PVP-VA, with the formation of an ASD confirmed and the solubility was enhanced compared with bulk RBM crystals. The SGR methodology has the possibility of contributing to process development in the pharmaceutical industry.

The objective of this research was to quantify the α-mangostin content in mangosteen pericarp (MP) ointment as a colloidal dispersion using near-infrared (NIR) spectroscopy. Various concentrations of MP (IP and EP) ointments containing both internal and external pericarps were prepared and the NIR spectra of these ointments were measured. The NIR spectrum of each ointment was correlated with α-mangostin concentration by partial least square (PLS) regression. Validation of the models was performed and their predictive ability was also investigated. The equation and R² value for the prediction of α-mangostin concentration in IP ointment were y = 0.9843x + 0.4441 and 0.9730 and those in EP ointment were y = 0.9569x + 0.1142 and 0.9136, respectively. The biases of the IP and EP ointment models were 0.23 and 0.00, respectively. The results showed that NIR could be a useful tool for the quality control of herbal medicine in hydrophilic ointment without any sample preparation. It could predict α-mangostin content in hydrophilic ointment at very low concentration with sufficient accuracy.

Disintegrating agents, such as microcrystalline cellulose (MCC), starch, carboxymethyl cellulose (CMC) and polyvinylpyrrolidone, are often used as drug additives to make the tablet swell and disintegrate in water. Here, we investigated the swelling process of these agents via near infrared and two-dimensional correlation spectroscopic analysis. The traditional agents MCC and starch showed increments of loose hydration prior to strong hydration. However, strong hydration increases were followed by loose hydration for CMC. In conclusion, the distinguishing swelling property of CMC is provided by the first strong hydration of water molecules, which may avoid polymer–polymer interaction and induce water penetration into the drug tablet.