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Multicomponent crystal is an effective way to improve the physicochemical properties of drugs. However, screening for co-formers that form multicomponent crystals with active pharmaceutical ingredients is still a challenge. In this study, a co-former prediction method based on partial least squares (PLS) regression was developed. First, 101 positive and negative samples reported were traced from the literature as a training set, based on which seven prediction models were built. Ciprofloxacin (CIP) was selected as the model drug, and the prediction models developed were adopted to predict co-formers which might form multicomponent crystals with CIP. Seven CIP multicomponent crystal systems were successfully prepared experimentally, six of which were hit by the two-parameter prediction model with the Hansen solubility parameter and the conductor-like screening model for real solvents, which achieved an overall accuracy and positive accuracy of 85 and 75%, respectively, higher than those of other models. All seven multicomponent crystal systems showed an increase in process solubility in pH 6.8 phosphate buffer solution (1.06–3.92-fold) and exhibited two different types of dissolution behaviors, wherein three samples exhibited a supersaturated peak in the dissolution process, while the other four did not. This difference was mainly due to the different rates of CIP trihydrate precipitation. The hygroscopic stability of all multicomponent crystals at room temperature and 95% relative humidity was substantially improved compared to raw CIP. This study provides a simple and effective strategy for the predictive screening of multicomponent crystal systems.

Disodium 5′-ribonucleotide, which is composed of disodium 5′-inosine (IMP) and disodium 5′-guanosine (GMP), is an important food additive. The lack of kinetic studies of it causes a lack of clarity in understanding the complicated multi-solute crystallization of IMP + GMP in ethanol-water. In this work, process analytical technology tools were used to obtain the thermodynamics and kinetic data from the experiments, the kinetic parameters of anti-solvent and cooling crystallization were investigated. The crystal form of IMP + GMP mixed crystal was determined, which was consistent with the IMP whether crystallized from pure water or ethanol-water. The effects of different anti-solvent addition rates and cooling rates on the metastable zone widths were studied, and the opposite effect on metastable zone width was found. The modified exponential empirical function was developed to correlate nucleation and growth kinetic equations under different conditions. The kinetic data were well fitted with adjusted correlation coefficient (adj-R2 > 0.7), which is sufficient to provide a valid reference for process design and control.

Chitosan-coated attapulgite (CCATP) was prepared and applied as sorbent for the sorptive removal of humic acid (HA) from aqueous solution. The effects of various factors such as solution cations, ionic strength and pH on the HA adsorption were investigated, and different models were used to fit the adsorption isotherms and the adsorption kinetics data. The results showed that after modified with chitosan, the HA sorption capacity enhanced greatly onto the attapulgite composites. In the experimental conditions, the sorption capacity of HA onto CCATP decreased with the increasing solution pH and increased with increasing ionic strength. The adsorption isotherms data fitted well with the Freundlich isotherm model (R2= 0.982), and the adsorption kinetics results could be better fitted by the pseudo-second-order model (R2= 0.911). The HA-loaded CCATP can be regenerated by using diluted NaOH solution. All results indicated that CCATP was a promising sorbent for removing HA from water.

Based on the decline in exploitation of coal resources, steep coal seam mining and mining face tensions continue to explore the feasibility analysis of steeply inclined faces in the gob. One of the key factors in utilizing the technology of gob-side entry retaining in steep coal seams is to safely and effectively prevent caving rock blocks from rushing into the gob-side entry by sliding downwards along levels. Using theoretical analysis and field methods, we numerically simulated the mining process on a fully-mechanized face in a steep coal seam. The stress and deformation process of roof strata has been analyzed, and the difficulty of utilizing the technology is considered and combined with practice in a steep working face in Lvshuidong mine. The feasibility of utilizing the technology of gob-side entry retaining in a steep coal seam has been recognised. We propose that roadways along the left lane offshoot body use a specially-made reinforced steel dense net to build a dense rock face at the lower head. The results show that the lane offshoot branch creates effective roof control, safe conditions for roadway construction workers, and practical application of steeply inclined gob.

Screening of co-formers for a specific active pharmaceutical ingredient is challenging during the development of multi-component crystals. Taking minoxidil (MIN) as a model drug, this study aims to examine the predictivity of the Cambridge Structural Database (CSD), Hansen solubility parameter (HSP), and the conductor-like screening model for real solvents (COSMO-RS) methods. First, CSD analysis based on a supramolecular approach was employed. Then, HSP and COSMO-RS methods were used to predict the cocrystallization possibility between MIN and 27 co-formers, where 10 candidate cases were reported. Based on the predicted results, eight aromatic carboxylic acids formed new solid forms with MIN experimentally, which met the criteria of Δδt< 7 MPa0.5and ΔHex< −2.00 kcal mol–1, respectively, and four single crystals of these were successfully obtained. Single-crystal X-ray diffraction and Hirshfeld surface analysis indicated that the proton transferred from co-formers to MIN, and seven new MIN multi-component crystals showed rapid release in the first 30 min (1.52- to 2.91-fold) with improved solubility. This study confirms the efficiency of the CSD method and demonstrates that the COSMO-RS method performs much better than the HSP method.