Novel strategy for encapsulation and targeted delivery of poorly water-soluble active substances

Carriers for targeted delivery and controlled release of poorly water-soluble active substances (PWSAS) are facing three challenges: (a) the encapsulation issues, (b) limitations of PWSAS water solubility, and (c) burst drug release which can be pharmacologically dangerous and economically inefficient. The present study brings a novel strategy for encapsulation and controlled release of PWSAS—caffeine in concentrations which are higher than its maximal water solubility without the possibility of burst effect. The modification of hydrophilic carrier based on poly(methacylic acid) was done using casein and liposomes. To further increase the maximal caffeine loading inside the carrier nicotinamide was used. The release study of the encapsulated PWSAS was elaborated with respect to morphology of the carriers and interactions that could be established between its structural components. The carriers swelling and the release of caffeine and nicotinamide were also investigated depending on caffeine concentration, the presence of different liposomal formulations and the volume ratio of liposomal formulation, in three media with different pH simulating the path of the carrier through the human gastrointestinal tract. The synthesized carriers are promising candidates for encapsulation of PWSAS in concentrations which are higher than its maximal water solubility and for the targeted delivery of those dosages.     

溶解结晶法制备磷酸一铵水溶肥

选取肥料级磷酸一铵为原料,采取溶解、除杂、一次蒸干或者浓缩重结晶的方法制得磷酸一铵水溶肥,通过讨论各工艺条件的影响,确定了较优的工艺条件:溶解温度96℃、溶解时间30 min、溶质过量1.1倍、沉降(60 min)+真空过滤。产品w(N+P2O5)≥60%,满足水溶肥料化工行业标准HG/T 4365—2012。此法开辟了粉状磷酸一铵新的用途,为於渣酸料浆法生产磷酸一铵水溶肥提供除杂依据和工艺参考。     

O-羧甲基壳聚糖在柠檬酸水溶液中的聚合工艺

利用O-羧甲基壳聚糖同时具有羧基、羟基和氨基等活性基团的特点,用柠檬酸为交联剂,可以使其发生聚合反应,生成不溶于水的高分子聚合物。通过对聚合产物产率的测算与分析,探讨了O-羧甲基壳聚糖在柠檬酸水溶液中的交联工艺参数对聚合物产率的影响。通过一系列单因素和正交试验,确定了最佳聚合工艺条件为:O-羧甲基壳聚糖溶液质量浓度为20 g/L,柠檬酸溶液质量浓度为40 g/L,反应pH值为6.0,反应温度为25℃,反应时间为10 min。     

水溶性C9石油树脂减水剂的制备及性能研究

将C9馏分、丙烯酸(AA)及马来酸单聚乙二醇酯进行自由基溶液共聚合制备水溶性C9石油树脂减水剂。采用红外光谱法对产物进行了表征和分析,考察了酯化反应条件,聚合反应条件如侧链长度、引发剂用量、反应温度及单体总浓度的影响,并对该减水剂进行了水泥净浆流动度等性能测试。实验结果表明所制备的减水剂具有优良的性能。     

自干型水溶性醇酸树脂的配方设计

建立了适合于水溶性醇酸树脂配方设计的通用程序。讨论了醇酸树脂的基本参数K、油度L、醇超量R及酸值Sv对醇酸树脂干燥时间和硬度的影响。结果表明当K=1、L=50%、R=1.2时,醇酸树脂膜有最短的干燥时间,所得膜的硬度也最高;Sv越大,干燥时间越长,但是膜的硬度越大。     

二氧化硅制备水溶性硅钾肥的研究

采用二氧化硅和碳酸钾为原料,通过高温煅烧活化二氧化硅制备水溶性硅钾肥。研究了煅烧温度、煅烧时间、氧化钾与二氧化硅物质的量比、二氧化硅粒径等条件对制备水溶性硅钾肥的影响,并通过热重-差示扫描量热法（TG-DSC）、X射线衍射（XRD）和扫描电镜（SEM）等对样品进行了表征。最佳工艺条件：煅烧温度为900 ℃,煅烧时间为30 min,氧化钾与二氧化硅物质的量比为0.85,二氧化硅平均粒径为160 μm。在此条件下制得的硅钾肥具有全水溶性,硅活化率为99.34%,有效硅（以二氧化硅计）质量分数为39.55%,氧化钾质量分数为53.23%。在高温下二氧化硅与碳酸钾的化学反应可抑制碳酸钾的挥发,反应产物的组成不仅含有硅酸钾（K₂SiO₃）,可能还存在二硅酸钾（K₂Si₂O₅）和四硅酸钾（K₂Si₄O₉）。     

Spray drying of drug-swellable dispersant suspensions for preparation of fast-dissolving,high drug-loaded,surfactant-free nanocomposites

Bioavailability of a poorly soluble drug can be improved by preparing a drug nanosuspension and subsequently drying it into nanocomposite microparticles (NCMPs). Unfortunately, drug nanoparticles aggregate during milling and drying, causing incomplete recovery and slow dissolution. The aim of this study is to investigate the impact of various classes of dispersants on drug dissolution from drug NCMPs, with the ultimate goal of enhancing the bioavailability of poorly water-soluble drugs via high drug nanoparticle loaded, surfactant-free NCMPs. Precursor suspensions of griseofulvin (GF, model drug) nanoparticles in the presence of various dispersants were prepared via wet stirred media milling and spray dried to form the NCMPs. Hydroxypropyl cellulose (HPC, polymer) alone and with sodium dodecyl sulfate (SDS, surfactant) was used as a base-line stabilizer/dispersant during milling. Two swellable crosslinked polymers, croscarmellose sodium (CCS) and sodium starch glycolate (SSG), and a conventional soluble matrix former, Mannitol, were used in addition to HPC. Besides being used as-received, CCS was also wet co-milled with GF for two different durations to examine the impact of CCS particle size. Laser diffraction, scanning electron microscopy, powder X-ray diffraction (XRD), UV spectroscopy, NCMP redispersion and dissolution tests were used for characterization. The results show that incorporation of CCS/SSG, preferably wet-milled to a wide particle size distribution, into the spray-dried NCMPs resulted in fast release and dispersion of drug nanoparticle clusters. The swellable dispersants were superior to Mannitol in dissolution enhancement, and could achieve fast release comparable to SDS, demonstrating the feasibility of spray drying to prepare high drug-loaded, surfactant-free nanocomposites.     

Potentials of proniosomes for improving the oral bioavailability of poorly water-soluble drugs

Objective: The objectives of this study were, first, to develop a free-flowing and stable proniosome formulation for poorly water-soluble drugs such as vinpocetine; and second, to estimate its bioavailability as oral drug delivery system.

Methods: The proniosomes consisting of span60, cholesterol, sorbitol and vinpocetine were prepared by a novel approach. After the proniosomes were contacted with water, the suspension of vinpocetine-loaded niosomes formed automatically. The proniosomes and reconstituted niosomes were evaluated for their physicochemical characteristics, in vitro drug dissolution and release, integrity and stability at different GI tract pH conditions, in situ single-pass intestinal perfusion and in vivo bioavailability.

Results: The proniosome powder exhibited excellent flowability. The reconstituted niosomes with high drug entrapment efficiency (89.67?±?3.28%) showed spherical morphology with smooth surface under transmission electron microscope (TEM). X-ray diffraction (XRD) indicated that the drug was in an amorphous or molecular state in proniosome powder. In vitro dissolution and release study, proniosomes did enhance the dissolution and release rate compared to vinpocetine suspension in phosphate buffer solution (pH 7.2). Proniosome-derived niosomes could keep their integrity and stability at different GI tract pH conditions. The in situ single-pass intestinal perfusion indicated that encapsulation of vinpocetine into niosomes could largely improved the absorption of vinpocetine. The AUC(0?∞) of F2 and F3 was about 4.0- and 4.9-fold higher than that of the vinpocetine suspension, respectively. The results demonstrated the proniosomes indeed remarkably enhanced the oral bioavailability of vinpocetine.

Conclusion: This study suggested the potential of proniosomes as stable precursors for the immediate preparation of niosome carrier systems.