Lenvatinib mesylate (LF), a multi-target tyrosinase inhibitor mainly used in the treatment of a variety of cancers, has low oral bioavailability mainly due to its gelation during the dissolution process. In the current study, in order to enhance dissolution and eliminate gelation of LF, a supramolecular coamorphous system of LF-baicalein (BAI) (molar ratio, 1∶1) was prepared by rotary evaporation and characterized by PLM, PXRD, DSC and FTIR. Results indicated the formation of coamorphous system with a single Tg of 118 °C. Different from original LF crystal, no gelation phenomenon was observed during the dissolution of coamorphous LF-BAI. In addition, the dissolution rate of LF was increased by 2.2-fold after coamorphization. Meanwhile, the dissolution rate of the co-former BAI was also enhanced by more than 25.4-fold. Stability test showed that the prepared coamorphous system had a good physical stability for at least 90 days under 25 °C/ 60%RH and 40 °C /75%RH conditions.

Lyotropic liquid crystal system is formed by the amphiphilic molecules dissolving in polar solvents with a special geometric structure. Lamellar, cubic and hexagonal mesophases are some of the most common lyotropic liquid crystal systems. Recently, they have attracted much research attention because of their distinctive structures and physico-chemical properties(like strong bioadhesion, high permeability, low liquidity, and slow released drug), and have been widely used as carriers for drug delivery systems, especially in transdermal and mucosal fields. According to the research about lyotropic liquid crystal and nasal route of administration in our group, and the related references in recent years, we investigate the technical strategies about the using of lyotropic liquid crystal in transdermal and mucosal drug delivery system. Among them, we specially put the emphasis on the application prospects of lyotropic liquid crystal in the nasal mucosal administration, and then provide a theoretical basis and future research directions in the development of lyotropic liquid crystal in transdermal and mucosal administration fields.

Myricetin(MYR)was cocrystallized with caffeine(CAF)by suspension and the single crystal of MYR-CAF cocrystal was cultured by slow solvent evaporation. Cocrystals obtained by two different methods were the same in crystal form after characterization with X-ray diffraction. Structural analysis of single crystal of MYR-CAF showed that its crystal system and the space group were monoclinic and P21/n, respectively. In MYR-CAF cocrystal, 4′-OH in ring B and 7-OH in ring A of MYR interacted with CAF at(8)C=N and(2)C=O through hydrogen bonds. In comparison to the original MYR crystal, the intrinsic dissolution rate of MYR was significantly enhanced for about 17-fold after cocrystallization with CAF.

In recent years, bio-metal organic frameworks (Bio-MOFs) synthesized with biocompatible ligands have been widely investigated as a potential drug delivery carrier due to their large specific surface area and porosity, rich host-guest intermolecular interactions, and good biocompatibility.In this review, we summarized the design methods of Bio-MOFs including structural and toxic factors, as well as a variety of drug loading methods including click chemistry, with particular focus on recent research advances in Bio-MOFs for pulmonary drug delivery systems, improving pharmaceutical properties of drugs, sustained and controlled drug release, stimulation response and targeted drug delivery systems.Finally, we summarized the bottlenecks that constrain the development of Bio-MOFs in clinical studies of actual pharmaceutical formulations and their future directions for approved formulations, aiming to provide some theoretical reference for promoting the application of Bio-MOFs in drug delivery systems.

In order to guarantee the quality of traditional Chinese medicines (TCMs), the crystallization transformation of complex extracts of TCMs and the influence of solid form on their physicochemical properties were studied.The extract of total flavonoids from Pueraria lobata was taken as a model.Crystallization transformation happened when lofting under different conditions, and the intrinsic dissolution tests were carried out.It was found that humidity was the key factor to induce crystallization of total flavonoids from Pueraria lobata.The greater the wettability was, the more the crystallization was.The dissolution rate of total flavonoids from Pueraria lobata with the most crystallization amount significantly decreased by 96.51% compared to the sample without crystallization.After further simulating the preparation process of total flavonoids from Pueraria lobata, it was found that the wet granulation process with introduced water would also lead to crystallization and reduced dissolution rate.As for all crystallization samples, there was an inversely proportional relationship between the dissolution rates and the amount of crystallization.The risk of crystallization existed both in the storage and preparation process of TCM extracts.Crystallization would significantly affect the dissolution rate, and thus the quality of TCM products.In this study, the crystallization transformation of amorphous complex TCM extracts was discovered, and the effect of the crystallization transformation on its dissolution behavior was systematically studied, which provides a new research idea for assuring the quality of TCM products and promoting the improvement of TCM preparation level.

Topical preparations for skin, including the commonly used dosage forms of ointments, creams, gels, patches and plasters, are convenient and can avoid the first-pass effect of drugs.Rheological study, which describes the flow characteristics and mechanical properties of products relevant to their Critical Quality Attributes, has become the main focus for topical preparations.Liquid and solid behaviors of products are usually investigated via steady rheology as well as dynamic rheology.This article reviews the research on topical preparations for skin and the data analysis models based on two rheological methods, aiming to provide some references for the rheological evaluation of topical preparations.

Baicalein(BE), a natural flavonoid mainly extracted from Radix Scutellaria, has comprehensive pharmacological actions such as anti-inflammation, anti-virus and anti-cancer activities. It belongs to BCS class II compound with relatively low oral bioavailability. The current study aims to improve its aqueous solubility and dissolution and hence to enhance its oral absorption by cocrystallization technique. Slurry crystallization method was employed to prepare baicalein cocrystal with co-former caffeine(CA), followed by physicochemical characterizations with DSC, XRPD and FTIR. Compared to BE and physical mixture of BE and CA, BE-CA cocrystal had a significantly higher dissolution of BE. In addition, in comparison to BE, this cocrystal achieved reduced time to peak(tmax)as well as significantly higher peak plasma concentrations(cmax)and area under the curve(AUCs)for both BE and its active metabolite baicalin(BI)in rats, suggesting enhanced the oral bioavailability of BE.

The purpose of this study was to investigate the formation thermodynamics of baicalein(BE)-nicotinamide(NCT)cocrystals in three solvents including ethyl acetate, acetone and trichloromethane. The solubilities of BE, NCT and BE-NCT in the above solvents at 25 °C were measured. Ternary phase diagrams(TPDs)of the BE-NCT-solvent systems were established. The non-linear fitting equation according to 1 ∶1 complexation mechanism of BE-NCT cocrystals demonstrated a good correlation between calculated and experiment data. ΔG0< 0 suggested that BE-NCT cocrystal formation was a spontaneous process. Among the organic solvents studied, the absolute value of ΔG0 in trichloromethane was significantly lower than that in the other two solvents. In addition, the cocrystallization zone in trichloromethane was far away from stoichiometric line. This study provides a theoretical foundation for solvent selection and preparation-condition optimization of BE-NCT cocrystals.

Abstract: It is well-known that crystal form of a drug is a key factor impacting the physicochemical properties of the drug, which in turn affects its in vivo efficacy, safety and stability. The study on crystal forms of solid-state drugs is crucial for drug quality control, selection of production process and evaluation of clinical efficacy. The combination of chemometric and analytical techniques exhibited its great ability to analyze a large amount of multidimensional data, providing the possibility for quantification of trace amount of crystals (< 1%). Meanwhile, using the process analytical technology (PAT) to monitor the crystal content real-time during prescription preparation process can further realize the control on formulation quality and serve as a core technology to support the patent protection of crystalline forms. In this review, the combined application of crystal analytical techniques and chemometric methods for the quantitative analysis of trace crystals were summarized, aiming to provide guidance for the manufacturing of pharmaceutical preparations and their quality control.