羟丙基甲基纤维素诱导丝素蛋白的构象转变

制备了羟丙基甲基纤维素 (HPMC)和丝素蛋白 (SF)的共混膜 ,用FTIR ,XRD和DSC方法对共混膜的结构进行了表征 ,讨论了HPMC对SF的构象转变作用 ,结果表明 ,HPMC能够有效的诱导SF的构象转变 ,HPMC的比例是影响SF的构象转变程度的重要因素 .当混入 3%～ 10 %HPMC时 ,SF的构象存在由无规线团或SilkI向SilkII(β 折叠 )的转变 ,当加入 7%HPMC时 ,β 折叠构象的比例最大 .从红外分析可知 ,构象转变是由于适量的HPMC与SF混合形成了二者之间的分子间氢键所致 .对不同比例的共混膜测定其在水中的溶出率 ,结果显示当HPMC的比例为 7%时SF几乎不溶于水     

硫酸铵水溶液中丙烯酰胺与正离子单体的分散共聚研究

以硫酸铵(AS)水溶液为介质,进行丙烯酰胺(AM)与正离子单体甲基丙烯酰氧乙基三甲基氯化铵(DMC)分散共聚合,制备出水溶性聚合物分散体.研究了盐浓度、分散稳定剂浓度及其分子量、单体浓度等对反应体系及分散体粒径的影响.结果表明,随着分散稳定剂的用量从6%增加到14%,分散体的平均粒径先下降,后又随之上升.分散稳定剂分子量越大,所得分散体的平均粒径越小.硫酸铵和单体的浓度对平均粒径和粒子形态等影响显著,只有在较小的范围内才能制备出粒径较均一的正离子型水溶性聚合物分散体;硫酸铵浓度越大,生成聚合物分子量越低.     

共无定形药物——新型单相无定形二元体系

共无定形药物是活性药物成分与其他小分子固体物质(药物或辅料)结合形成的具有单一玻璃化转变温度的单相无定形二元体系。它作为一种新的药物固体形态,可能改善药物的溶解度、溶出速率、稳定性及生物利用度等理化性质,已成为药物研发的一种新途径。本文主要对共无定形药物的定义、形成机理、制备方法、分析鉴别方法、物理化学稳定性以及溶解度和溶出速率进行综述,并对共无定形与固体分散体和共晶的比较进行了概述。     

甲醇氧化PtSnCo/C阳极催化剂

通过乙二醇液相分步还原法制备了金属质量分数为20%的PtSn/C二元及PtSnCo/C三元催化剂.采用X射线衍射(XRD)光谱法、能量散射谱(EDS)对催化剂进行了表征;通过阳极线性伏安扫描法(LSV)、连续循环伏安法(CV)、预吸附单层CO溶出法研究了其电化学性质.结果表明,PtSnCo/C三元催化剂较商业化JM-PtRu/C催化剂具有更好的氧化甲醇催化活性.循环伏安扫描100圈后发现,PtSn/C二元催化剂的甲醇氧化峰电流快速衰减到其初始氧化峰电流的11%左右,而PtSnCo/C三元催化剂仅衰减到其初始值的50%左右,这表明PtSnCo/C三元催化剂具有更好的化学稳定性.在PtSnCo/C催化剂上,甲醇氧化起始电位比直接吸附CO后的CO阳极溶出电位负,意味着甲醇在PtSnCo/C催化剂上氧化的中间产物不是CO,而是比CO更为活泼且易于氧化的中间物种.     

单分散氧气锌纳米粒子的制备及表征

用羟丙基甲基纤维素(HPMC)为空间分散剂,制备了前驱物[Zn2(OH)2CO3*HPMC],焙烧后得到的纳米ZnO同不加HPMC制备的ZnO相比较,产物粒度小、分散均匀、不易团聚.通过XRD, TEM及FT-IR对产物的组成、粒径及形貌进行了表征.利用UV-Vis测试了产物的光吸收性能,结果表明,所得的产物在200nm～400nm具有较强的吸收.     

(BCO)12与(CH)12稳定性的环张力分析

基于密度泛函理论的B3LYP方法, 对具有等瓣相似性的(BCO)12和(CH)12的10种异构体结构的稳定性进行了计算对比研究, 这10种异构体由三元、四元、五元和六元环组成. 环张力分析表明对羰基硼笼体系, 三元环起主要的稳定化作用, 而四元环是张力的主要来源, 对碳氢笼体系, 五元环起主要的稳定化作用. 电子差分密度表明羰基硼笼中的三元环与碳氢笼中的三元环有不同的电子结构, 导致了它们不同的张力表现. 核独立化学位移(NICS)分析表明, 尽管σ芳香性不是稳定性的决定因素, 但对笼的稳定性有一定的影响.     

聚合物多元醇分散体的流变特性

聚合物多元醇分散体(以下简称分散体)是接枝聚醚多元醇、聚醚多元醇和乙烯基单体聚合物的混合物,直接用于制备高回弹、高负载和阻燃的软质和半软质聚氨酯泡沫体,是新一代聚醚多元醇产品[1].分散体用于聚氨酯工业中各种产品的生产,除要求有良好的稳定性外,其最为重要的指标是粘度应小于3000mPa·s和乙烯基单体聚合物的含量(固含量)应大于40%.但分散体的粘度,随固含量的增加呈指数性增加[2].近年来,已有既具高固含量和良好稳定性,又有较低粘度的分散体的研究报道[3].本文在不同的反应条件下,合成了分散体,测定了其流变特性和体系中微粒的大小…     

超细全硫化粉末丁腈橡胶对聚氯乙烯性能的影响

制备了PVC/超细全硫化粉末丁腈橡胶(NBR-UFPR)二元、PVC/NBR-UFPR/纳米CaCO3三元复合材料,研究了3种NBR-UFPR(平均粒径分别为150nm、90nm和70nm)对硬质PVC性能的影响.测试结果表明,3种NBR-UFPR均可同时提高硬质PVC的热稳定性、耐热性和韧性.透射电镜(TEM)照片显示,3种NBR-UFPR均能以单个粒子均匀分散在PVC基体中,NBR-UFPR与PVC相间的界面积大于传统的PVC/弹性体共混物.PVC/NBR-UFPR/纳米CaCO3三元复合材料具有更高的热稳定性、耐热性和韧性,TEM照片显示,在三元复合材料中,分散相粒子间的平均距离进一步减小.     

碳前驱体在全氟磺酸型碳基固体酸材料设计中的影响

以碳纳米管、介孔碳分子筛和氮掺杂的介孔碳为前驱体,采用全氟磺酸-全氟乙烯共聚物(PTFE)液相沉积方法制备了修饰量相同的三种全氟磺酸功能化碳基固体酸催化剂,利用N₂吸附、热重分析(TG)、透射电子显微镜(TEM)、傅里叶红外变换(FTIR)光谱以及电位滴定等方法对材料的结构和酸性进行了表征.考察催化剂对于苯甲醇与苯甲醚Friedel-Crafts (F-C)反应的催化性能.结果表明,前驱体的比表面积越大,与修饰剂的相互作用越强,越有利于修饰剂在前驱体表面的分散,得到的催化剂表面酸量越多,酸催化活性越好.因此,全氟磺酸功能化的氮掺杂介孔碳在F-C反应中表现出最高的活性和稳定性.     

Bicine单电荷阴离子与芳香氮碱形成的三元金属离子混配配合物的稳定性研究

用pH电位滴定法首次研究了水溶液中三元混配配合物M(Bic)L+(M2+=Ni2+或Zn2+,L=苯并咪唑、吡啶、3,4-二甲基吡啶、异喹啉,Bic- = N,N-双(羟乙基)甘氨酸的单电荷阴离子)的稳定性.三元混配配合物相对于二元配合物的稳定性差值用ΔlgKM =lgKM(Bic)M(Bic)L-lgKMML来表示.结果表明这些三元混配配合物比统计规律所估计的要稳定得多,且ΔlgKZn 大于ΔlgKNi.三元混配配合物稳定性增大可归因于πA-πB协同作用和Zn2+配位构型的转变.     

Characterization of solid dispersions of rofecoxib using differential scanning calorimeter

Summary Solid dispersions were prepared to enhance the dissolution rate of rofecoxib. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used for the characterization of solid dispersions of polyvinyl pyrrolidone (PVP):talc:drug (3:1:1) and hydroxypropyl methylcellulose (HPMC):talc:drug (4:1:1). The DSC study indicated that PVP solid dispersion showed formation of fusion solution while HPMC solid dispersion showed no intermolecular fusion during the preparation of solid dispersions by spray dry process. The dissolution profiles and the calculated times for 75 and 90% drug release showed that dissolution rate of rofecoxib was improved in solid dispersions as compared to pure drug and physical mixtures. The DSC and XRD were successfully employed to find out the crystalline state of drug in the both solid dispersions. PVP solid dispersion gave better dissolution rate than HPMC solid dispersion. The drug was transformed from crystalline to amorphous form in PVP solid dispersion which was further conformed by XRD and DSC. The PVP:talc:drug solid dispersion can be used for the dissolution enhancement and thereby bioavailability of rofecoxib.     

Stability and solution concentration enhancement of resveratrol by solid dispersion in cellulose derivative matrices

Resveratrol is a highly biologically active phytoalexin, found in many plant materials that are common elements of the human diet, such as grapes, nuts, and red wine. The therapeutic or disease preventative potential of this natural polyphenolic antioxidant has been limited in part due to its poor aqueous solubility and low oral bioavailability. We hypothesized that solid dispersion of resveratrol (Res) in cellulose derivative matrices might afford amorphous dispersions, from which supersaturated Res solutions would be produced in the human gastrointestinal (GI) tract, resulting in higher Res bioavailability. We carried out structure–property studies employing cellulose esters with a range of physical characteristics but possessing features suitable for use in amorphous solid dispersions: carboxymethylcellulose acetate butyrate (CMCAB), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and cellulose acetate adipate propionate (CAAdP). The cellulose derivative results were compared with those of a negative control, pure crystalline Res, and a positive control, Res/poly(vinylpyrrolidinone) (PVP). Solid dispersions were characterized by powder X-ray diffraction (XRPD), modulated differential scanning calorimetry (MDSC), nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FT-IR) of solid dispersions. HPMCAS and PVP solid dispersions afforded faster and more complete Res release at pH 6.8; however Res is also released from PVP matrices at pH 1.2. The carboxyl-containing cellulose derivatives release Res to only a small extent at pH 1.2. This combination of solution and solid phase stabilization against crystallization, and pH-triggered drug release makes these cellulose esters attractive candidates for Res bioavailability enhancement.     

Solubility, dissolution rate and bioavailability enhancement of irbesartan by solid dispersion technique

The objective of present work was to enhance the solubility and bioavailability of poorly aqueous soluble drug Irbesartan (IBS). The solid dispersions were prepared by spray drying method using low viscosity grade HPMC E5LV. Prepared solid dispersions were characterized by dissolution study, fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction studies (XRD). Results of the SEM, DSC and XRD study showed the conversion of crystalline form of IBS to amorphous form. The dissolution rate was remarkably increased in case of solid dispersion compared to pure IBS. Solubility and stability of solid dispersion was increased due to surfactant and wetting property, slowing devitrification and having anti-plasticization effect of HPMC E5LV. In vivo studies were performed in healthy rabbits (New Zealand grey) and compared with plain IBS. Solid dispersions showed increase in relative bioavailability than the plain IBS suspension. In conclusion, the prepared solid dispersions showed remarkable increase in solubility, dissolution rate and hence bioavailability of poorly water soluble drug Irbesartan.     

Miscibility of nifedipine and hydrophilic polymers as measured by (1)H-NMR spin-lattice relaxation

The miscibility of a drug with excipients in solid dispersions is considered to be one of the most important factors for preparation of stable amorphous solid dispersions. The purpose of the present study was to elucidate the feasibility of (1)H-NMR spin-lattice relaxation measurements to assess the miscibility of a drug with excipients. Solid dispersions of nifedipine with the hydrophilic polymers poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose (HPMC) and alpha,beta-poly(N-5-hydroxypentyl)-L-aspartamide (PHPA) with various weight ratios were prepared by spray drying, and the spin-lattice relaxation decay of the solid dispersions in a laboratory frame (T(1) decay) and in a rotating frame (T(1rho) decay) were measured. T(1rho) decay of nifedipine-PVP solid dispersions (3 : 7, 5 : 5 and 7 : 3) was describable with a mono-exponential equation, whereas T(1rho) decay of nifedipine-PHPA solid dispersions (3 : 7, 4 : 6 and 5 : 5) was describable with a bi-exponential equation. Because a mono-exponential T(1rho) decay indicates that the domain sizes of nifedipine and polymer in solid dispersion are less than several nm, it is speculated that nifedipine is miscible with PVP but not miscible with PHPA. All the nifedipine-PVP solid dispersions studied showed a single glass transition temperature (T(g)), whereas two glass transitions were observed for the nifedipine-PHPA solid dispersion (3 : 7), thus supporting the above speculation. For nifedipine-HPMC solid dispersions (3 : 7 and 5 : 5), the miscibility of nifedipine and HPMC could not be determined by DSC measurements due to the lack of obviously evident T(g). In contrast, (1)H-NMR spin-lattice relaxation measurements showed that nifedipine and HPMC are miscible, since T(1rho) decay of the solid dispersions (3 : 7, 5 : 5 and 7 : 3) was describable with a mono-exponential equation. These results indicate that (1)H-NMR spin-lattice relaxation measurements are useful for assessing the miscibility of a drug and an excipient in solid dispersions.     

Investigation and physicochemical characterization of vinpocetine-sulfobutyl ether beta-cyclodextrin binary and ternary complexes

The purpose of this study was to investigate the interactions between vinpocetine (VP), sulfobutyl ether beta-cyclodextrin (SBEbetaCD) and the water-soluble polymers polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC). The water-soluble polymers were shown to improve the complexation efficiency of SBEbetaCD, and thus less SBEbetaCD was needed to prepare solid VP-SBEbetaCD complexes in the presence of the polymers. The interactions between VP and SBEbetaCD, with or without PVP or HPMC, were thoroughly investigated in aqueous solutions using the phase-solubility method as well as in the solid state. The amount of VP solubilized in water or aqueous polymer solution increased linearly with increasing SBEbetaCD concentration, demonstrating A(L)-type plots. We estimated the apparent stability constant (K(c)) at room temperature of VP-SBEbetaCD binary complex to be 340 M(-1) and this value increased to 490 M(-1) or 390 M(-1), respectively, with the addition of PVP and HPMC, assuming a 1 : 1 VP-SBEbetaCD molar ratio. Improvement in the K(c) values for ternary complexes clearly confirmed the benefit of the addition of water-soluble polymers to promote higher complexation efficiency. Solid VP-SBEbetaCD binary and ternary systems were prepared by physical mixing, kneading, coevaporation, and lyophilization methods and fully characterized by scanning electron microscopy, differential scanning calorimetry, and X-ray diffractometry. The results obtained suggest that coevaporation and lyophilization methods yield a higher degree of amorphous entities and indicated formation of VP-SBEbetaCD binary and ternary complexes.     

Cyclodextrin solubilization of celecoxib: solid and solution state characterization

The low aqueous solubility of celecoxib (CCB) hampers its oral bioavailability and permeation from aqueous environment through biological membranes. The aim of this study was to enhance the aqueous solubility of CCB by complexation with cyclodextrin (CD) in the presence of water-soluble polymer. The effects of different CDs (αCD, βCD, γCD, 2-hydroxypropyl-β-cyclodextrin and randomly methylated β-cyclodextrin (RMβCD)) and mucoadhesive, water-soluble polymers (hydroxypropyl methylcellulose (HPMC), chitosan and hyaluronic acid) were investigated. The phase solubility profiles and CCB/CD complex characteristics were determined. RMβCD exhibited the greatest solubilizing effect of the two CDs tested. However, γCD was also selected for further investigations due to its safety profile. Addition of polymer to the aqueous CD solutions enhanced the CD solubilization. Formation of CCB/RMβCD/HPMC and CCB/γCD/HPMC ternary complexes resulted in 11 and 19-fold enhancement in the apparent complexation efficiency in comparison to their CCB/CD binary complex, respectively. The size of ternary complex aggregates in solution were determined to be from about 250 to about 350 nm. The data obtained from Fourier transform infra-red, differential scanning calorimetry and powder X-ray diffraction indicated presence of CCB/CD inclusion complexes in the solid state. Proton nuclear magnetic resonance data demonstrated that CCB was partially and totally inserted into the hydrophobic central cavities of RMβCD and γCD.     

Screening of mucoadhesive microparticles containing hydroxypropyl-beta-cyclodextrin for the nasal delivery of risperidone

Interaction of the antipsychotic drug risperidone with hydroxypropyl-beta-cyclodextrin (HPBCD) in solution and in the solid state was studied with the aim of overcoming the limitations associated with nasal administration of low solubility drugs. Risperidone solubility studies revealed inclusion complex formation with a 1:1 stoichiometry. Low concentrations (0.1 w/v %) of hydroxypropylmethyl cellulose (HPMC) and carbomer affected risperidone solubility in water. No formation of a ternary complex was detected. The solid inclusion complex was prepared by spray drying and was characterised by thermal (DSC) and spectral (FTIR) analyses. Risperidone and the inclusion complex were loaded into microparticles by spray drying using HPMC, carbomer and HPMC/carbomer interpolymer complex (IPC) as mucoadhesive components. The microparticles were characterised with respect to drug loading, particle size distribution, thermal analysis, and zeta potential measurements. Mucoadhesive properties of the microparticles were studied by measuring the work of adhesion. Carbomer and IPC based microparticles revealed superior mucoadhesive microparticles compared to HPMC based microparticles. Drug incorporation into microparticles reduced their mucoadhesive properties, while incorporation of the cyclodextrin complex caused no additional reduction in mucoadhesion. The in vitro dissolution studies showed that formation of the inclusion complex significantly increased the risperidone dissolution rate from the microparticles, thus providing sustained drug release.     

Preparation and evaluation of binary and ternary inclusion complexes of fenofibrate/hydroxypropyl-β-cyclodextrin

This study aimed to investigate the effect of hydroxypropyl methylcellulose on the complexation of fenofibrate and hydroxypropyl-β-cyclodextrin (HP-β-CD). Initially, phase solubility studies with an excess amount of drug in the HP-β-CD solutions with and without hydroxypropyl methylcellulose (HPMC) were investigated. Both of the binary and ternary complexes were prepared by ball-milling. The complexes were characterized by Fourier transform infrared spectroscopy (FI-IR), X-ray powder diffraction (XPRD), differential scanning calorimetry (DSC) and nuclear magnetic resonance spectroscopy (¹H-NMR). The A_L type phase-solubility diagram revealed that the complexes of fenofibrate and HP-β-CD were formed with molecular ratio of 1:1. The results of FT-IR, XPRD, DSC and ¹H NMR analysis show the formulation of inclusion complexes. In conclusion, the interaction occurrs between fenofibrate and HP-β-CD in the complexes, and the existence of HPMC effectively improves the complexation efficiency and stability constant. The in vitro dissolution test suggests ternary complex is superior to binary complex in terms of the release of fenofibrate.     

Statistical optimization of tamsulosin hydrochloride controlled release pellets coated with the blend of HPMCP and HPMC

The objective of the present study was to evaluate three coating parameters for the application of a blend of HPMCP and HPMC in ethylcellulose aqueous dispersions (Surelease) in order to obtain controlled release of tamsulosin hydrochloride. The selected independent variables, HPMCP content (X1), HPMC content (X2) and coating level (X(3)), were optimized with a three-factor, three-level Box-Behnken design. The selected dependent variables were the cumulative percentage values of tamsulosin hydrochloride that had dissolved after 2, 3 and 5 h. Various dissolution profiles of the drug from controlled release pellets were obtained. Optimization was performed for X1, X2 and X3 using the following target ranges; 15% < or = Y1 < or= 30%; 50% < or = Y2 < or = 65%; 80% < or = Y3 < or = 95%. Results of the optimization procedure indicated that the optimized levels of HPMCP content (X1), HPMC content (X2) and coating level (X3) were 30%, 15% and 25%, respectively. Controlled release pellets coated with the optimized formulation provided a release profile that was close to predicted values. In addition, the dissolution profiles of the controlled release pellets coated with the optimized formulation were similar to those of the commercial product Harunal capsule (f1 = 4.6, f2 = 78.7).     

Combined effect of hydroxypropyl methylcellulose and hydroxypropyl-β-cyclodextrin on physicochemical and dissolution properties of celecoxib

Investigation on the influence of hydroxypropyl methylcellulose (HPMC) on solubility and dissolution properties of celecoxib/hydroxypropyl-β-cyclodextrin system was carried out, with the ultimate goal of enhancing the drug bioavailability. ¹H-NMR and ¹³C-NMR spectroscopy were first performed to elucidate the type of interactions between celecoxib (CEL) and hydroxypropyl-β-cyclodextrin (HP-β-CD). Then, solubility studies in the absence and in the presence of HPMC were carried out in aqueous solution. After heating in autoclave of CEL/HP-β-CD/HPMC suspensions a synergistic increasing effect on the aqueous solubility of CEL was observed. In fact, the presence of both HP-β-CD (0.05 M) and HPMC (0.25% w/v) gave rise to a 330-fold CEL solubility increase, whereas the cyclodextrin alone provided a 34-fold increase. Gibbs free energy values calculated from phase solubility data were all negative, indicating the spontaneous nature of CEL solubilization, and they decreased in the presence of HPMC, demonstrating that the solubilization conditions became more favorable. CEL/HP-β-CD and CEL/HP-β-CD/HPMC solid systems (physical mixtures and coevaporated products) were characterized by differential scanning calorimetry and infrared spectroscopy. Results suggested that the coevaporation method yields a high degree of amorphous entities and indicated the formation of a CEL/HP-β-CD complex in the coevaporated products. The positive effect of HPMC is particularly evident when looking at the CEL dissolution rate from the binary and ternary solid systems. Specifically, the percent of CEL dissolved after 10 min. resulted 84.21% for ternary coevaporated product and 50.18% for binary coevaporated product with respect to 13.10% for the drug alone.