Mixing processes are important for making high-quality pharmaceutical formulations and are related to dissolution and chemical stability in pharmaceutical manufacturing.

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.

No abstract

Dynamic light scattering (DLS) is used for measuring average particle diameter and particle diameter distribution of nano-sized particles dispersed in liquid. The parameters are important characteristics mainly for drug delivery system (DDS) formulations, such as solid in oil (S/O) formulations, liposome formulations, suspension formulations, and emulsion formulations. Herein are described a measurement method and measurement case of particle diameter analysis of medical products using laser light.

The polymorphic relationship between optically active (R)- and for racemic (RS)-forms of 1,2-distearin and 1,2-dipalmitin were studied by X-ray diffraction, infrared spectrum, and the thermal analysis. These glycerides have two crystalline forms, α and β, wherein α is metastable and β is stable under ordinary conditions. The α→β transformation for the (RS)-1,2-distearin crystal was extremely slow as compared with that for the (R)-form crystal, implying that the β-form crystal of (RS)-1,2-distearin is an eutectic mixture of small (R)- and (S)-crystals while the α-form crystal of (RS)-1,2-distearin is composed of a replacement type solid solution of (R)- and (S)-1,2-distearin molecules. Almost the same results were obtained with 1,2-dipalmitin, for which the rate of α→β transformation is higher than that for the 1,2-distarin, probably because of a higher mobility of this compound.