Formation, physical stability and in vitro antimalarial activity of dihydroartemisinin nanosuspensions obtained by co-grinding method

The purpose of this study was to investigate the formation of drug nanoparticles from binary and ternary mixtures, consisting of dihydroartemisinin (DHA), a poorly water-soluble antimalarial drug, with water-soluble polymer and/or surfactant. Binary mixtures of drug/polyvinyl pyrrolidone K30 (PVP K30), binary mixtures of drug/sodium deoxycholate (NaDC), and ternary mixtures of drug/PVP K30/NaDC were prepared at different weight ratios and then ground by vibrating rod mill to obtain ground mixtures. Nanosuspension was successfully formed after dispersing ternary ground mixtures or DHA/NaDC ground mixtures in water. The ternary ground mixtures did not give superior nanosuspension in terms of particle size reduction and recovery of drug nanoparticles, but they provided more physically stable nanosuspensions than DHA/NaDC ground mixtures. The size of drug nanoparticles was decreased with increasing grinding time and lowering amount of PVP K30 and NaDC. About 95% of drug nanoparticles were found in the nanosuspension from ternary ground mixtures. Zeta potential measurement suggested that stable nanosuspension was attributable to adsorption of NaDC and PVP K30 onto surface of drug particles. Atomic force microscopy and transmission electron microscopy with selected area diffraction indicated that DHA in nanosuspension was existed as nanocrystals. The obtained nanosuspensions had higher in vitro antimalarial acitivity against Plasmodium falciparum than microsuspensions. The results suggest that co-grinding of DHA with PVP K30 and NaDC seems to be a promising method to prepare DHA nanosuspension.     

Solid State Interaction of Raloxifene HCl with Different Hydrophilic Carriers During Co-grinding and its Effect on Dissolution Rate

This study investigated the effects of different classes of hydrophilic carriers (poly vinyl pyrrolidones [PVPs] [Plasdone K-25 and Plasdone S-630], cellulosic polymers [hydroxypropyl methyl cellulose and hydroxy propyl cellulose], and Sodium Alginate) on the solid state and dissolution rate of Raloxifene hydrochloride (R-HCl). Solid state characterizations of co-ground mixtures and physical mixtures in 1:1 and 1:2 ratios of drug to polymer were performed by employing laser diffractometer for particle size and differential scanning calorimetry (DSC) for solid state interactions. The results of particle size studies showed that only co-grinding with PVPs was more effective in the reduction of particle size than the milling of drug alone. DSC study indicated that the crystalline nature of the drug was reduced after co-grinding with PVPs when compared with their corresponding physical mixtures. The hydrophilic carriers other than PVPs did not reduce the crystalline nature of the drug significantly. X-ray diffraction and scanning electron microscopy were carried out for selected batches to confirm DSC results. Significant enhancement in dissolution rate and extent was observed with co-ground mixtures of drug and PVPs. Plasdone S-630 was found to be a better carrier for R-HCl in terms of achieving improvement in dissolution. In vitro dissolution data can be described by Hixson–Crowell model, indicating the drug release mechanism predominated by erosion.     

Lignin-containing Microfibrillated Cellulose Prepared from Corncob Residue via Calcium Hydroxide Co-grinding and Its Application in Paper Reinforcement

In this study, lignin-containing microfibrillated cellulose (MFC) was prepared from corncob residue after xylose extraction via co-grinding with calcium hydroxide. The product was then compared with the MFC obtained by direct grinding and applied to strengthen paper. The chemical composition and morphological structure analysis results showed that the corncob residue can be used to prepare lignin-containing MFC and does not require further purification. Moreover, the co-grinding with calcium hydroxide is easier to fibrillate corncob residue. The MFC obtained by co-grinding with calcium hydroxide had a higher aspect ratio, and its surface was coated with calcium carbonate nanoparticles. MFCs obtained by both the methods mentioned above had an obvious strengthening effect on paper. Compared with the paper without MFC, the tensile index, elongation, burst index, and folding strength of the paper with MFC obtained by co-grinding with calcium hydroxide significantly increased by 17.5%, 22.1%, 19.5%, and 157.1%, respectively. This study provides a novel idea for the utilization of corncob residue, which may enhance the value and promote the comprehensive utilization of corn by-products.     

Formation,Physical Stability and In Vitro Antimalarial Activity of Dihydroartemisinin Nanosuspensions Obtained by Co-grinding Method

The purpose of this study was to investigate the formation of drug nanoparticles from binary and ternary mixtures, consisting of dihydroartemisinin (DHA), a poorly water-soluble antimalarial drug, with water-soluble polymer and/or surfactant. Binary mixtures of drug/polyvinyl pyrrolidone K30 (PVP K30), binary mixtures of drug/sodium deoxycholate (NaDC), and ternary mixtures of drug/PVP K30/NaDC were prepared at different weight ratios and then ground by vibrating rod mill to obtain ground mixtures. Nanosuspension was successfully formed after dispersing ternary ground mixtures or DHA/NaDC ground mixtures in water. The ternary ground mixtures did not give superior nanosuspension in terms of particle size reduction and recovery of drug nanoparticles, but they provided more physically stable nanosuspensions than DHA/NaDC ground mixtures. The size of drug nanoparticles was decreased with increasing grinding time and lowering amount of PVP K30 and NaDC. About 95% of drug nanoparticles were found in the nanosuspension from ternary ground mixtures. Zeta potential measurement suggested that stable nanosuspension was attributable to adsorption of NaDC and PVP K30 onto surface of drug particles. Atomic force microscopy and transmission electron microscopy with selected area diffraction indicated that DHA in nanosuspension was existed as nanocrystals. The obtained nanosuspensions had higher in vitro antimalarial acitivity against Plasmodium falciparum than microsuspensions. The results suggest that co-grinding of DHA with PVP K30 and NaDC seems to be a promising method to prepare DHA nanosuspension.     

Environmentally clean synthesis of diphenylmethanes using silica gel-supported ZnCl2 and FeCl3

Lewis acids such as FeCl₃ and ZnCl₂ were supported on silica gel, alumina, zirconia and titania by co-grinding with anhydrous Lewis acids in appropriate proportions in an agate mortar. The catalysts have good shelf life and reusability. Synthesis of diphenylmethanes with these catalysts was studied; silica gel was the best support. © 1998 SCI     

Sucralose as co-crystal co-former for hydrochlorothiazide: development of oral disintegrating tablets

Development of oral disintegrating tablets requires enhancement of drug dissolution and selection of sweetener. Co-crystallization of drugs with inert co-former is an emerging technique for enhancing dissolution rate. The benefit of this technique will become even greater if one of the sweeteners can act as co-crystal co-former to enhance dissolution and mask the taste. Accordingly, the objective of this work was to investigate the efficacy of sucralose as a potential co-crystal co-former for enhancing the dissolution rate of hydrochlorothiazide. This was extended to prepare oral disintegrating tablets. Co-crystallization was achieved after dissolving hydrochlorothiazide with increasing molar ratios of sucralose in the least amount of acetone. The co-crystallization products were characterized using Fourier transform infrared spectroscopy, differential thermal analysis and powder X-ray diffraction. These measurements indicated that co-crystallization process started at a drug sucralose molar ratio of 1:1 and completed at 1:2. The developed co-crystals exhibited faster drug dissolution compared with the control, with co-crystal containing the drug with sucralose at 1:2 molar ratio being optimum. The later was used to prepare fast disintegrating tablets. These tablets had acceptable physical characteristics and showed fast disintegration with subsequent rapid dissolution. The study introduced sucralose as co-crystal co-former for enhanced dissolution and masking the taste.     

茶多酚-高直链玉米淀粉共研磨混合物的制备与结构表征

为了提高抗性淀粉的含量,以茶多酚(TPs)和高直链玉米淀粉(HAMS)为原料,利用研磨技术制备茶多酚-淀粉共研磨混合物,通过X射线衍射、扫描电子显微镜和热重分析对其结构、形貌和热稳定性进行表征,并采用模拟体外消化方法对其营养片段(快消化淀粉、慢消化淀粉、抗性淀粉)进行评价。X-射线衍射表明,随着球磨时间的延长,所得共研物中淀粉的结晶衍射峰强度逐渐减弱,经3 h球磨的处理后,淀粉的结晶度由38.1%降低到8.3%。扫描电镜结果表明:淀粉颗粒膨胀,颗粒形状发生形变,表面变得相对粗糙,部分颗粒发生破裂,茶多酚与淀粉在共研磨过程中发生聚集粘连。热重分析结果表明,所得共研磨物较高直链玉米淀粉的稳定性低,但比茶多酚的热稳定性高。经共研磨处理后,当TPs与HAMS质量比由1:50增加到1:10时,所得共研磨物的抗性淀粉含量由6.31%±0.88%增加到31.92%±1.53%。经过共研磨处理后茶多酚-高直链玉米淀粉共研磨混合物的结晶度降低,形态发生变化,表面变得粗糙,颗粒黏连,热稳定性降低,抗性淀粉的含量增加。