With the rapid advancement of science and technology, the application of 3D printing technology for personalized drug manufacturing is becoming increasingly sophisticated.Compared to traditional manufacturing technology, 3D printing can easily customize preparations with specific sizes, shapes and release behaviors for personalized drug use.This review summarizes the principles of several 3D printing technologies commonly used in drug manufacturing, lists the unique advantages and application examples of 3D printing technology for pharmaceutical preparation, analyses the current research status and development trends of the global industry of drug 3D printing, and summarizes the current problems and challenges facing drug 3D printing, aiming to provide some guidance for researchers of 3D printed drugs.

Most drugs taste bitter and irritating, resulting in poor compliance of patients, and the bad odor affects the therapeutic effect. The successful research and development of a drug should not only conform to the five quality characteristics of effectiveness, stability, safety, uniformity and economy, but also the compliance of patients to drugs with bad odor. The development of taste masking techniques is critical for bitter drugs.This review describes the principles, advantages and drawbacks of traditional taste masking techniques, and introduces the mechanism and application of novel taste masking techniques, such as melt granulation, hot melt extrusion, 3D printing, drug complex preparation, and bitter taste inhibitors. The in vitro evaluation methods of drug taste masking effect, such as functional magnetic resonance imaging, in vitro dissolution, and electronic tongue technology, are described. And introduce in vivo evaluation methods, such as animal and human taste, in the field of taste masking effect. A new strategy of BP neural network prediction model for drug taste evaluation is proposed, with a view to providing theoretical reference for the future research on drug taste masking.

The poorly water-soluble drug curcumin was prepared into oral nanocrystalline solid preparation by nanocrystal technology to improve the solubility, dissolution rate, and bioavailability. Curcumin nanocrystals were prepared by media grinding technology, and two types of stable curcumin nanocrystal suspension formulations were developed. The stabilizers in the two formulations were polyvinylpyrrolidone (PVP K30)/sodium lauryl sulfate (SDS)(1∶1) and Tween 80, respectively. The prepared curcumin nanocrystal suspension was loaded onto microcrystalline cellulose pellets through fluidized bed coating technology, and the nanocrystalline capsules were obtained after filling. The results of nanocrystal redispersion stability and scanning electron microscope (SEM) showed that the morphology of drug-loaded pellets was uniform when PVP K30 and SDS were used as stabilizers, and the diameter of nanocrystals before and after redispersion was about 200 nm, which was determined as the optimal formulation. In vitro dissolution study showed that curcumin nanocrystals at the size of 200 nm exhibited significantly promoted dissolution. The results of X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) showed that the curcumin crystalline partly turned amorphous during the preparation of nanocrystals.Pharmacokinetic studies in rats showed that the bioavailability of curcumin nanocrystals was 9.3 times higher than that of the bulk drug. The curcumin nanocrystalline capsules developed in this research can significantly improve the dissolution rate and bioavailability, which is of great significance in improving the poor solubility of drugs, and is expected to become a new dosage form for clinical treatment.

Biological toxins are toxic molecules produced by specific microorganisms,plants or animals.Due to their wide range of sources and high toxicity,the availability of protein and non-protein toxins is becoming increasingly important,some of which are used for military purposes and developed as biotoxin warfare agents.In this paper,the classification and mechanism of action of biological toxins are discussed.In addition,the strategies for prevention and control of biological toxins as well as their therapeutic applications are reviewed.

Objective: To introduce the design of modified Reading man flap, and observe the clinical effect of modified flap for repairing digit and toe wounds. Methods: From July 2014 to September 2017, dorsal skin defects on 37 digits and 18 toes were repaired with our modified Reading man flaps. The revised design was characterized with enlargement the major flap and extending the minor flap proximally, and all donor site defect were sutured primarily through the major flap recover the defect and the minor flap repair the subsequent donor defect. Results: All the detects in 55 patients were repaired by the modified Reading man flaps with direct donor sites closure. With average of 11.5 months (9.5-25.7 months) follow-up, all flaps survived with satisfactory texture and appearance, the bulky deformity and scar contracture did not occur. Partial necrosis of tip in the minor flaps occurred in 2 toes and healed by wound dressing. The function of the toe joints was good and the walking gait was normal. Partially impaired PIP joint function with limited flexion occurred in 2 cases. Based on the TAM evaluation criteria, the results were excellent in 28 digits, good in 7 digits, and the overall satisfactory rate was 94.6%. Conclusions The modified Reading man flap can get good clinical effects for treatment of the digit and toe dorsal skin defect with the advantages of simple procedure, easy transfer and direct closure of donor sites. Flaps appearance and joints function can get good result postoperatively.

OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.

OBJECTIVE To evaluate the palatability and chewability of chewable tablets， and provide reference for the quality evaluation of various types of chewable tablets. METHODS Using self-made Glucosamine hydrochloride chewable tablets as the model drug， the quality test was conducted. The in vitro simulation system for chewable tablets was established by using a texture analyzer and rheometer， and an oral simulation experiment was conducted on chewable tablets. The texture analyzer was used to measure the force required for chewing and simulate the static disintegration process of chewable tablets； the rheometer was adopted to measure the viscoelasticity， thixotropy， and deformability of chewable tablets during the chewing process. RESULTS The disintegration time limit， principal component content， and dissolution of self-made Glucosamine hydrochloride chewable tablets all met the limit requirements. The in vitro simulation results of the texture analyzer showed that self-made chewable tablets were easy to chew in both axial and radial directions， and the force required for chewing was within the range of the chewing force of the teeth； chewable tablets could disintegrate at an appropriate time without being chewed and only taken in the oral cavity. The in vitro simulation results of the rheometer showed that the chewable tablets in the oral cavity exhibited a behavior of elasticity as the main factor and viscosity as the secondary factor through the continuous stirring of the tongue， and the viscosity of the chewable tablets gradually decreased with tongue stirring or tooth chewing； when chewing with teeth， the internal force of the chewing tablets decreased， causing plastic deformation and crushing. After being crushed， the shape couldn’t be restored， making it easy to chew and swallow. CONCLUSIONS The combination of texture analyzer and rheometer can be used to simulate the oral chewing process and evaluate the palatability and chewability of self-made Glucosamine hydrochloride chewable tablets. This model can provide reference for the evaluation of various chewable tablets.