With microscopic thermogravimetric analysis, it is difficult to prepare metastable intermediate phases with precise water contents during the dehydration process of hydrates, making it a challenge to acquire their related spectra. The gradual dehydration process of ZnSO₄·7H₂O proceeds through 7 → 6 → 4 → 1 → 0. Vibrational spectra of ZnSO₄ hydrates, especially ZnSO₄·6H₂O and ZnSO₄·4H₂O, have not been previously reported. By macroscopic thermogravimetric analysis of ZnSO₄·7H₂O, the dehydration process can be precisely controlled to produce a variety of ZnSO₄ hydrates with specific water contents. In this study, powder X-ray diffraction confirmed the purities of 7H₂O, 6H₂O, 4H₂O, 1H₂O and anhydrous ZnSO₄. IR and Raman spectra of ZnSO₄ hydrates were obtained and compared for the first time. Spectroscopic and crystallographic analysis revealed that structural similarity plays a key role in the 7 → 6 → 4 → 1 → 0 dehydration process. Macroscopic thermogravimetric analysis combined with powder X-ray diffraction is a valuable method for investigating the intermediate phases in the hydrate dehydration process.

Spray drying of poorly water-soluble drugs in organic solvents is a mature process in the preparation of drugs amorphous solids dispersions (ASDs). The use of organic solvents is under increasing environmental protection and safety pressure and restricts the application of advanced polymers as proteins which are usually insoluble and unstable in organic solvents. Aqueous solution spray drying technology is a candidate method for preparing ASDs without the use of organic solvents. Increasing temperature and adding volatile additives can improve the solubility of poorly water-soluble drugs in water without introducing additional components and energy needed. In this work, ammonia assisted aqueous solution spray drying method was successfully used to prepare various ASDs of indomethacin (25%) with synthetic polymers as polyvinylpyrrolidone and proteins as β-lactoglobulin, lactalbumin hydrolysate, bovine serum albumin, with high yields, special micro golfs morphology, precise compositions and longtime stabilities, compared to high-temperature aqueous solution spray drying method. ASDs with lactalbumin hydrolysate and bovine serum albumin show better dissolution profiles than other ASDs. Aqueous solution spray drying is easily extended to prepare the ASDs of sulfamerazine and celecoxib, providing a possibility to avoid the use of organic solvents in advanced ASDs preparations via spray drying.

Amorphous solid dispersion (ASD) technology is popularly used for enhancing the solubility of poorly water-soluble drugs. Drug molecules in ASDs can be dispersed in the form of either amorphous (AASD) or molecular (MASD) forms. The boundary between AASDs and MASDs (A–M boundary) is defined as the drug concentration at which the existence of MASDs obviously influences the physicochemical properties of ASDs. In this work, fluorescence spectroscopy based on the aggregation-caused quenching (ACQ) phenomenon was used to determine the A–M boundary of curcumin (CUR) ASDs prepared via neat ball milling. The relationship between the fluorescence intensity and the loading of CUR in the sample is consistent with the Stern–Volmer equation. For the CUR ASDs with PVP, the samples with CUR loading below 10% show significantly increased fluorescence and have a higher solubility (~178 μg·mL⁻¹), suggesting the A–M boundary is around 10%. Similar A–M boundaries around 10% were also observed for CUR ASDs with PVPVA, Soluplus, HPMC, and HPMCAS. It is of great significance to define the A–M boundary of ASDs for guiding pharmaceutical ASD formulas by balancing drug loading, stability, and solubility.