One Step In Situ Co-Crystallization of Dapsone and Polyethylene Glycols during Fluidized Bed Granulation.

Several studies have demonstrated the feasibility of in situ co-crystallization in different pharmaceutical processes such as spray drying, hot melt extrusion, and fluidized bed granulation (FBG) to produce co-crystal-in-excipient formulations. However, no previous studies have examined such a one step in situ co-crystallization process for co-crystal formulations where the coformer is a polymer. In the current study, we explored the use of FBG to produce co-crystal granules of dapsone (DAP) and different molecular weight polyethylene glycols (PEGs). Solvent evaporation (SE) was proven to generate DAP-PEGs co-crystals at a particular weight ratio of 55:45 w/w between DAP and PEG, which was subsequently used in FBG, using microcrystalline cellulose and hydroxypropyl methyl cellulose as filler excipient and binder, respectively. FBG could generate co-crystals with higher purity than SE. Granules containing DAP-PEG 400 co-crystal could be prepared without any additional binder. DAP-PEG co-crystal granules produced by FBG demonstrated superior pharmaceutical properties, including flow properties and tableting properties, compared to DAP and DAP-PEG co-crystals prepared by SE. Overall, in situ co-crystallization via FBG can effectively produce API-polymer co-crystals and enhance the pharmaceutical properties.

Real-time differential refractometry without interferometry at a sensitivity level of 10(-6).

We present a refractometer based on the principle of total internal reflection that can sensitively record, in real time, the refractive index of fluids over a wide range of refractive indices. The device uses a divergent laser beam and a linear diode array, and has no mechanical or optical moving parts, enabling us to achieve the measurement of a refractive index at a sensitivity level of 10(-6). Our refractometer does not rely on interferometry, thus enabling the device to be compact, portable, and inexpensive. To the best of our knowledge, this is the first time a noninterferometric device that performs real-time differential refractometry with a sensitivity of better than 10(-5) has been demonstrated in the literature. We show that our experimental results agree very well with Fresnel theory. We establish a theoretical limit on the sensitivity of this class of refractometers.