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The Influence of Liquid-Solid Preparations on the Dissolution of Suvorexant
Barbara Jadach1, Nikola Pawlak1
1Division of Industrial Pharmacy, Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 3 Rokietnicka, 60-806 Poznan, Poland.
Abstract:
This study aimed to evaluate the impact of liquid-solid (LS) systems on the dissolution profiles of a poorly soluble drug-suvorexant (SUV). In the first stage of this study, LS systems were prepared by using two different non-volatile solvents: ethylene glycol diethyl ether and polyethylene glycol 400 (PEG 400). To compare the properties of different types of LS systems, formulations were prepared that differed in the content of SUV (10 and 20 mg) as well as in the ratio of excipients (microcrystalline cellulose and colloidal silica), which was 10:1 or 1:1. The physicochemical properties of the prepared formulations were characterized by X-ray diffractometry (XRD), thermogravimetry (TGA) and differential scanning calorimetry (DSC). This was followed by a dissolution study of SUV from prepared LS systems, using a 0.4% sodium lauryl sulfate solution as the medium to maintain sink conditions. Results showed that the LS systems change the crystalline structure of SUV to an amorphous one and improve the dissolution rate of SUV. The greatest improvement was achieved by using the microcrystalline cellulose and colloidal silica in a 10:1 ratio for the preparation of the system (CCA variant). It was observed that the type of solvent used and the order of combining excipients during the preparation of LS systems are also important for the properties. The main point was that physicochemical characterization of the prepared formulations lead to a loss of crystallinity of SUV associated with its introduction into liquid-solid systems.
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This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...

