Cocrystal formation of niclosamide and urea in supercritical CO2 and impact of cosolvent

A cocrystal of niclosamide and urea was attempted for the first time using a crystallization in supercritical solvent (CSS). Experiments were conducted at 40 °C or 60 °C between 3.3 and 29.4 MPa in CO2. Cocrystal formation showed a dependence on the state of CO2 with no cocrystal formation below the critical point and consistently showed partial conversion above the critical point. The addition of 0.5 mL (2.7–3.5 mol%) cosolvent was found to have significant impact on cocrystal formation at 40 °C and 20 MPa. Addition of 2-propanol increased cocrystal formation by between 50 % and 60 % compared to neat scCO2, while cyclohexane reduced cocrystal formation by between 20 % and 35 %, and water completely hindered cocrystal formation. The impact of hold time, cosolvent, solubility in relation to ternary phase diagrams, and inter- and intra-molecular hydrogen bonding are discussed

Solubility of 2,5-Di-tert-butylhydroquinone and Process Design for Its Purification Using Crystallization

The solubility of 2,5-di-tert-butylhydroquinone (DTBHQ) in acetone, ethyl acetate, methanol, and the mixtures of ethanol and water was measured and correlated in the temperature range between 278.95 K and 346.15 K. It was found that the solubility in acetone increases more rapidly with increasing temperature than in other solvents. The data was correlated using the modified Apelblat, Buchowski-Ksiazczak λh, and Van’t Hoff equations, with a maximum relative average deviation of less than 2.74 %. The obtained thermodynamic models were used in designing a crystallization process and synthesizing a flowsheet for effective purification of crude DTBHQ from the byproduct of tertiary butylhydroquinone (TBHQ)

Investigation of the solid state properties of amoxicillin trihydrate and the effect of powder pH

The purpose of this research was to investigate some physicochemical and solid-state properties of amoxicillin trihydrate (AMT) with different powder pH within the pharmacopoeia-specified range. AMT batches prepared using Dane salt method with the pH values from 4.39 to 4.97 were subjected to further characterization studies. Optical and scanning electron microscopy showed that different batches of AMT powders were similar in crystal habit, but the length of the crystals increased as the pH increased. Further solid-state investigations using powder x-ray diffraction (PXRD) demonstrated the same PXRD pattern, but the intensity of the peaks raised by the powder pH, indicated increased crystallinity. Differential scanning calorimetry (DSC) studies further confirmed that as the powder pH increased, the crystallinity and, hence, thermal stability of AMT powders increased. Searching for the possible cause of the variations in the solid state properties, HPLC analysis showed that despite possessing the requirements of the United States Pharmacopoeia (USP) for purity/impurity profile, there was a direct relationship between the increase of the powder pH and the purity of AMT, and also decrease in the impurity I (α-Hydroxyphenylglycine) concentration in AMT powder. Recrystallization studies confirmed that the powder pH could be controlled by adjusting the pH of the crystallization