Abstract The indomethacin-nicotinamide cocrystal was prepared by hot melt extrusion(HME)to improve the dissolution of indomethacin in vitro. The optimum preparation conditions were investigated using temperature and rotate speed as variables. Thermogravimetric analysis(TGA), determination of content and determination of related substances were performed to evaluate the thermal stability of indomethacin during the process. Cocrystal was also prepared by solution crystallization from acetonitrile. The products obtained by the two methods were characterized by differential scanning calorimetry(DSC), Fourier transform infrared(FTIR)and powder X-ray diffraction(PXRD). The solubility and dissolution advantages of cocrystal were evaluated. The results showed that the HME method could successfully prepare the indomethacin-nicotinamide cocrystal at 115 °C and eutectic mixture was formed during the process. The cocrystal significantly improved the solubility and dissolution of indomethacin in deionized water, with pH 5. 5 and pH 6. 8 phosphate buffer. The preparation of poorly soluble drug cocrystal by HME can significantly improve its solubility, providing new idea for the development of poorly soluble drugs and HME technology.

3D printing is rapidly developing in various areas of science and technology. Owing to its advantages such as simplicity, flexibility, reproducibility and suitability, 3D printing technology is utilized in the field of advanced pharmaceutical preparations. The literatures are mainly related to the formulations with a variety of release mechanism, including conventional-release formulations, controlled-release formulations, implants and compound preparations. Herein the latest 3D printing technology in the advanced preparations is presented and the related developing trends and challenges are also addressed.

To improve the theraputic effect of chemotherapeutic drugs, D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)was employed as a carrier of mitoxantrone(MTO). MTO was successfully conjugated to TPGS via succinic anhydride to prepare TPGS-MTO prodrug. The prodrug was then self-assembled into TPGS-MTO micelle, with the particle size of(25. 61±0. 92)nm, the polydispersity of 0. 22±0. 04 and the Zeta potential of -(3. 98±0. 09)mV. The micelle was homogeneous spheres under the observation of transmission electron microscope(TEM). The drug loading capacity(DLC)was(18. 61±0. 24)% by HPLC. Meanwhile, the particle size of TPGS-MTO micelle remained stable in 24 h. TPGS-MTO showed a controlled drug release profile with only 9. 04% MTO being detected in 24 h in neutral conditions, and faster release was achieved by decreasing pH in media. Cellular uptake experiments showed that micelle was 1. 18 times more effective than parent drug after 6 h incubation on MCF-7 cells. The cytotoxicity of micelle on MCF-7 and MCF-7/MDR cells was detected by MTT, both with anti-tumor activity, especially on MCF-7/MDR cells. In conclusion, TPGS-MTO prodrug micelle could be a potential formulation of higher therapeutic effects and fewer side-effects than MTO itself.

Wax matrix tablets is a special pharmaceutical controlled release preparation. However, it has not yet been fully studied and applied. In this article, the progress in carriers and techniques for the preparation of wax matrix tablets in recent years was reviewed. Analysis and comparison of their advantages and disadvantages can help to promote the application of wax matrix tablets in the future.

Folic acid(FA)was conjugated with bovine serum albumin(BSA)to form targeting material. BSA-coated cationic nanostructure lipid carriers(BSA-cNLCs)and folate-BSA-coated cationic nanostructure lipid carriers(FA-BSA-cNLCs)were prepared by film dispersion. The particle sizes of BSA-cNLCs and FA-BSA-cNLCs were 81. 4 nm and 79. 8 nm, while their Zeta potentials were +5. 12 mV and +3. 74 mV. Both nanostructure lipid carriers showed spherical shape. Paclitaxel encapsulation efficiency of them were more than 97%, with drug loading efficiency of about 3. 7%. In vitro experiments confirmed that the uptake of FA-BSA-cNLCs by overexpressed folate receptor SKOV3 cells was significantly higher than that of BSA-cNLCs, demonstrating that FA-BSA-cNLCs were obviously targeted to SKOV3. Blood and tumor pharmacokinetics showed that there was no significant differences between BSA-cNLCs and FA-BSA-cNLCs. This suggested that modified FA on the surface of the preparation had no effect on its in vivo behavior. Tumor inhibition of BSA-cNLCs and FA-BSA-cNLCs were 72. 08% and 80. 75%, repectively, which indicateds that FA-BSA-cNLCs improve anticancer efficacy in vitro and in vivo, and that it could be a potential preparation for the treatment of cancer.

To construct nanostructured lipid carriers(NLCs)with different particle sizes but the same other physicochemical properties, central composite design was adopted. Coumarin-6(C-6)was selected as the model drug due to its high lipophilicity and high fluorescence intensity. Physicochemical properties of NLCs with 100 nm, 200 nm and 300 nm in particle size could remain stable during certain time in K-R solution and PBS. Release experiments in vitro showed that cumulative release of C-6 in NLCs was less than 7% after 24 h. The MTT assay indicated that both blank NLCs and C-6 loaded NLCs showed low toxicity. To confirm the integrity of NLCs in gastrointestinal tract, DiR-loaded NLCs were prepared and the distribution in vivo was monitored by fluorescence imaging. After 6 h oral administration, intact DiR-loaded NLCs could stiu be found, suggesting that NLCs could be used to characterize the uptake in gastrointestinal tract.

Abstract: Lipoproteins are biological lipids carriers. The natural and reconstituted lipoprotein based drug delivery systems have been extensively developed in recent years. This article reviews the development of natural and reconstituted low-density lipoprotein and high-density lipoprotein based vehicles in the antitumor area.

In this study, indomethacin (IND) loaded solidified-polymeric micelles (IND-SPM) were prepared. Their in vitro characteristics were investigated. Methoxy-poly(ethylene glycol) poly(D, L-lactide) copolymer (mPEG-PDLLA) was used as IND carrier. The preparation of IND-SPM was conducted by solution-absorption method and evaporation by rotary evaporator. Polyplasdone XL-10 was used as adsorbent. The solution-absorption method was conducted by the following procedure; IND and mPEG-PDLLA were dissolved in acetone, followed by addition of polyplasdone XL-10 and stirred to obtain a suspension. The powder of IND-SPM was simply obtained after the organic solvent was completely evaporated. More than 90% (w/w) of IND (20 mg) in the powder was dissolved in 250 mL PBS within 30 min. DSC, 1H NMR and SEM results proved that IND was encapsulated within mPEG-PDLLA. The solubility of IND in the system increased 4.6 times with the highest amount of copolymer. The solidified particles were found to be suitable for the formulation of tablets or capsules.

This study is to prepare the microemulsion-based gel based on the W/O microemulsion and fluorouracil (5-Fu) as a model drug to study the transdermal characterization and observe its skin irritation of the microemulsion-based gel in vitro. IPM acted as oil phase, AOT as surfactant, Tween 85 as cosurfactant, water was added dropwise to the oil phase to prepare W/O microemulsion at room temperature using magnetic stirring, then 5-Fu powder was added. The gelatin was used as substrate to prepare 5-Fu microemulsion-based gel. The permeation flux of 5-Fu from 5-Fu microemulsion-based gel across excised mice skin was determined in vitro using Franz diffusion cell to study the influence of the amount of gelatin and the drug loading capacity. Refer to 5-Fu cream, the irritation of microemulsion and microemulsion-based gel on the rat skin was studied. Based on the water/AOT/Tween 85/IPM microemulsion, only the gelatin can form the microemulsion-based gel. At 25 degrees C, 32 degrees C and 40 degrees C, the amount of gelatin required for the formation of microemulsion-based gel were 7%, 14% and more than 17%, respectively. The 12 h transdermal cumulated permeation amount of 5-Fu from microemulsion-based gel containing 14% gelatin and 0.5% drug loading were (876.5 +/- 29.1) microg x cm(-2), 12.3 folds and 4.5 folds more than 0.5% 5-Fu aqueous solution and 2.5% (w/w) 5-Fu cream, respectively. Microemulsion-based gel exhibited some irritation, but could be subsided after drug withdrawal. Microemulsion-based gel may be a promising vehicle for transdermal delivery of 5-Fu and other hydrophilic drug.

Aim:To prepare vinblastine-loaded PCL-PEG_(6000)-PCL nanoparticles,and to study their physicochemi-cal properties and in vitro antitumor activity.Methods: PCL-PEG_(6000)-PCL triblock copolymer was prepared by ring-opening polymerization,and vinblastine-loaded PCL-PEG_(6000)-PCL nanoparticles was prepared by coprecipita-tion.The morphous,particle size,polydisperse index,particle yield,the drag-loading content,the encapsulation ef-ficiency and in vitro release rate of these vinblastine-loaded nanoparticles were determined.The cytotoxicity of vinblastine-loaded nanoparticles to K562/A02 leukimia cell line was determined by MTT assay.Results: It was found using transmission electron microscopy(TEM)that the nanoparticles exhibited a spherical shape with core-shell structure.The particle sizes of the nanoparticles obtained by dynamic light scattering were(185 ± 2.7)nm.The drug loading content and the encapsulation efficiency were determined to be 28.83% and 86.52%,re-spectively.In vitro release study revealed that more than 70% of accumulative release of entrapped vinblastine was reached in 9 hr and that nearly complete release was achieved in 24 hr.The inhibition of vinblastine-loaded nanoparticles to K562/A02 cell line was significantly increased as compared with that of the same dose of sulfate vinblastine solution.Conclusions: PCL-PEG-PCL nanoparticles could be used as a carrier of vinblastine,and the prepared nanoparticles exhibited a spherical shape,high encapsulation efficiency,relevant stablity and sustained-release properties.The eytotoxicity of vinblastine to K562/A02 cell line was significantly increased when it was encapsulated in PCL-PEG-PCL nanoparticles.