不同介质对甲壳胺-替加氟缓释作用的影响

目的研究甲壳胺-替加氟缓释片在不同介质中的释放性质。方法以甲壳胺为辅料,采用湿颗粒法制备甲壳胺-替加氟缓释片,分别以盐酸溶液(0．1mol／L)、磷酸盐缓冲液(pH6．8)、蒸馏水为介质采用转篮法测定其释药情况,并与市售替加氟片作对比．结果甲壳胺-替加氟缓释片在0．1mol／L盐酸溶液中可持续释放达12h以上,而在蒸馏水及磷酸盐缓冲液中1h已释放达90％以上。结论甲壳胺-替加氟缓释片的缓释作用对介质pH值的依赖性较强。     

挤出造粒、气流包衣法制备包衣微粒剂．Ⅴ．去羟肌苷肠溶微粒的制备和药动学研究

用挤出造粒、气流包衣法研制了去羟肌苷肠溶微粒，药物在0．1mol／L盐酸中2h不降解，在pH6．8磷酸盐缓冲液中10min的释放率达75％以上。Beagle犬体内的药动学研究证明，制得的去羟肌苷肠溶微粒相对生物利用度是去羟肌苷分散片的169％。     

豆豉溶栓酶肠溶片剂的制备及体外释放度

采用均匀设计优化豆豉溶栓酶肠溶片片芯的制备工艺。结果表明，按优化处方经工艺过程制得的片芯酶活性损失仅6％。包肠溶衣后的制品在0．1mol／L盐酸中2h平均累积释放率为2．1％；在0．2mol/L磷酸钠缓冲液（pH6．8）中，23．4min累积释药50％，45min释药86．3％，释药规律符合Weibull分布模型。     

海藻酸钙凝胶微丸作为口服缓释给药载体的研究

将海藻酸钠溶液滴入胶凝剂氯化钙溶液中制备了海藻酸钙凝胶微丸。以胶凝过程中凝胶微丸重量变化 (失水量 )研究了胶凝速率及不同浓度海藻酸钠溶液 ( 1 %～ 4 % )与氯化钙溶液 ( 0 0 5～0 2 0mol/L)对胶凝速率的影响 ,结果是 6h前胶凝速率快 ,随后减慢 ,约 70h胶凝完全 ,氯化钙溶液的浓度≥ 0 1mol/L对胶凝速率无明显影响。干燥的凝胶微丸在不同水性介质中溶胀试验结果表明 :在温度约 37℃时 ,微丸在蒸馏水和 0 1mol/L盐酸 ( pH1 0 )中几乎不溶胀 ,而在磷酸盐缓冲溶液( pH6 8)中1h溶胀 ,溶胀后的微丸直径是干燥前湿微丸直径的 1 80 %。海藻酸钙凝胶微丸这种溶胀的 pH敏感性 ,使它能成为口服药物缓释制剂的载体。以硝苯地平为模型药物制备的海藻酸钙凝胶微丸 ,其体外释放试验结果 ,2h累积释放量为 2 0 %～ 30 % ,6h为 6 0 %～ 80 % ,1 2h时大于85 %。药物从微丸中的释放是以扩散和骨架溶蚀相结合的方式。由此可见 ,硝苯地平的海藻酸钙凝胶微丸具有缓释作用     

羧甲基壳聚糖/聚乙烯醇水凝胶处方及制备工艺优化

目的：优选羧甲基壳聚糖（CMCS）／聚乙烯醇（PVA）水凝胶的处方及制备工艺；初步考察载药水凝胶的体外释药规律。方法：合成不同取代度的CMCS；以羧甲基壳聚糖的取代度，2％戊二醛的用量及温度为考察因素，各取三水平，以水凝胶在pH1．2溶液中的膨胀率为考察指标进行L9（3^4）正交实验；并以甲硝唑为模型药物，对水凝胶的体外释药做初步考察。结果：取代度为0．38的CMCS，在0．2mL的2％戊二醛做交联剂于室温下交联，有最大膨胀率（24．54±1．04）（n=3）；以最佳条件制备的甲硝唑水凝胶于0．1mol·L^-1盐酸溶液中在8h内累积释药率达（89．95±1．05）％（n=3）。结论：CMCS/PVA水凝胶最佳处方在pH1．2时具有理想的膨胀率，可做为胃部释药载体进一步研究。     

盐酸恩丹西酮包芯缓释片的研制

目的　研制盐酸恩丹西酮包芯缓释片。方法　采用HPMC为骨质材料,通过正交设计试验优选最佳处方和工艺,考察释放介质pH值对缓释片释药特性的影响。结果及结论　释放介质pH值对盐酸恩丹西酮包芯缓释片释药影响较大,在酸性介质及中性蒸馏水中 2 4h释药完全(≥ 95 %),在 pH6 8磷酸盐缓冲液中释药不完全( <4 5 % ),0～ 14h体外释放符合零级动力学过程。     

羟丙基甲基纤维素的凝胶特性及其对曲尼司特缓释片释放行为的影响

目的：研究羟丙基甲基纤维素(HPMC)的凝胶特性及其对曲尼司特缓释片释放行为的影响。方法：采用称重法、图像法和体积测量法,研究HPMC辅料片和曲尼司特缓释片在不同pH环境中的水合度和溶胀度。结果：辅料片在SGF和SIF中的水合速率常数分别为0.897 h-1和0.681 h-1;溶胀速率常数分别为1.005 h^-1和0.713 h^-1。曲尼司特缓释片在SGF中,在0.5 h内迅速水合和溶胀,其后呈负增长;而在SIF中,重量和体积都缓慢增加,5 h后重量稍有下降,体积保持不变。结论：HPMC水凝胶的形成速度和形态与介质的pH有关,凝胶层的溶蚀速度控制药物的释放。     

8个不同厂家盐酸洛美沙星胶囊体外溶出度比较

目的：比较8个不同厂家生产的盐酸洛美沙星胶囊的体外溶出情况,以考察产品质量。方法：采用转篮法（转速为100r／min）进行体外溶出度试验,以紫外分光光度法测定洛美沙星的含量,分别以盐酸溶液（0．1mol／L）、水、磷酸盐缓冲液（pH6．8）和醋酸盐缓冲液（pH4．0）为溶出介质,测定盐酸洛美沙星胶囊的溶出度。结果：8个厂家的盐酸洛美沙星胶囊在盐酸溶液（0．1mol／L）的溶出介质中30min溶出量均达到80％以上,在其他不同溶出介质中溶出差异大。结论：不同厂家产品质量和生产工艺存在差异。     

载盐酸普萘洛尔的SWELSTARTM MX-1骨架片及羟丙甲纤维素骨架片体外释药的比较

以水溶性药物盐酸普萘洛尔为模型药,分别制备了SWELSTARTM MX-1(下称MX-1)骨架片和羟丙甲纤维素(HPMC)骨架片.考察了两种空白骨架片在4种介质[0.1 mol/L盐酸、pH 6.8和7.2磷酸盐缓冲液(PBS)、水]中的吸水膨胀和溶蚀情况.结果表明,介质的pH和离子强度对MX-1骨架片的吸水膨胀和溶蚀无显著影响,而对HPMC骨架片的影响较大.采用零级、一级、Higuchi和Ritger-Peppas模型拟合两种骨架片在4种介质中的释药行为.结果表明,HPMC骨架片在pH 7.2 PBS中的释放比其他3种介质中快,而MX-1骨架片在4种介质中的释放行为没有明显变化.两种骨架片在4种介质中的释药机制均为药物扩散和骨架溶蚀协同作用,累积释放率数据均符合Ritger-Peppas模型.本研究表明,MX-1比HPMC有更好的抗高离子强度能力.     

阿莫西林/克拉维酸钾原料及制剂中有关物质测定方法的比较

目的建立两种HPLC线性梯度洗脱测定阿莫西林／克拉维酸钾有关物质的方法，并对其进行比较。方法两种方法均采用C18柱，流速1．0mi／min，所用流动相为磷酸盐缓冲液：乙腈色谱系统。方法一中流动相A为0．05mol／L磷酸盐缓冲液（pH5．0）；乙腈（99：1），流动相B为0．05mol／L磷酸盐缓冲液（pH5．0）：乙腈（80：20）；方法二中流动相A为0．01mol／L磷酸盐缓冲液（pH6．0），流动相B为0．01mol／L磷酸盐缓冲液（pH6．0）：乙腈（20：80）。两种方法的梯度变化不同。方法一和方法二的检测波长分别为254和215nm。结果两种方法的线性范围、检测限及测定结果基本一致。结论两种方法准确，专属性强，灵敏度高，适用于阿莫西林／克拉维酸钾中有关物质测定，且方法一的稳定性优于方法二。     

Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum

The aim of this study was to investigate the influence of pH, buffer species and ionic strength on the release mechanism of chlorpheniramine maleate (CPM) from matrix tablets containing chitosan and xanthan gum prepared by a hot-melt extrusion process. Drug release from hot-melt extruded (HME) tablets containing either chitosan or xanthan gum was pH and buffer species dependent and the release mechanisms were controlled by the solubility and ionic properties of the polymers. All directly compressed (DC) tablets prepared in this study also exhibited pH and buffer species dependent release. In contrast, the HME tablets containing both chitosan and xanthan gum exhibited pH and buffer species independent sustained release. When placed in 0.1N HCl, the HME tablets formed a hydrogel that functioned to retard drug release in subsequent pH 6.8 and 7.4 phosphate buffers even when media contained high ionic strength, whereas tablets without chitosan did not form a hydrogel to retard drug release in 0.1N HCl. The HME tablets containing both chitosan and xanthan gum showed no significant change in drug release rate when stored at 40 °C for 1 month, 40 °C and 75% relative humidity (40 °C/75% RH) for 1 month, and 60 °C for 15 days.     

吲哚美辛酶解型结肠靶向片的初步研究

采用湿法制粒压片制备吲哚美辛瓜尔胶骨架片,并测定了模拟人体胃肠道生理环境下的体外释放度.结果表明,骨架片5h内释药不超过20%;26h内不加酶组的总释药量不超过40%,加酶组为88%左右,能达到结肠靶向给药的效果.     

阿替洛尔非pH依赖型缓释片的制备及处方优化

以羟丙甲纤维素为缓释材料,琥珀酸为pH缓冲剂制备非pH依赖型阿替洛尔缓释片.考察以不同用量的羟丙甲纤维素和琥珀酸配制成不同处方缓释片,测定各个处方在0.1mol/L盐酸和pH7.4磷酸盐缓冲液中的释放度,采用多指标同步优化筛选处方.结果表明,优化处方在不同pH介质中均有较好的缓释效果.     

Water uptake and relaxation processes in mixed unlimited swelling hydrogels

The rheological oscillatory test parameters have been observed for highly concentrated hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose-sodium (NaCMC) and mixed HPMC/NaCMC hydrogels obtained by swelling of matrix tablets in 0.1 mol cm(-3) HCl and pH 6.8 phosphate buffer. The mechanical spectra of the gels have been analysed using theoretical models, i.e. a generalised Maxwell model and an adapted Maxwell model, both based on Ferry and Williams approximations. The relaxation time spectra as well as the parameters characteristic of linear viscoelastic behaviour have been calculated: zero shear viscosity (eta(0)), plateau moduli (G(N)(0), G(0)' and G(0)"), zero-relaxation time (tau(0)) and mean relaxation time (θ). The mechanical spectra of mixed HPMC/NaCMC hydrogels differ considerably from those of the pure ones, the type of the spectrum depending on the two polymers' ratios. In both media, the rheological models applied define the HPMC gels as homogeneous entangled networks, and those of NaCMC and mixed HPMC/NaCMC as heterogeneous physical gels. The relationship between the kinetic constants of water penetration and the mean relaxation times suggests that the molecular relaxation controls the water uptake velocity. With all the systems tested irrespective of pH of the aqueous phase, an inversely proportional dependence between the viscosity and the water penetration velocity has been noted. Since the degree of hydration is one of the factors determining the degree and velocity of drug release from the hydrogel matrices, the relation between the kinetic parameters of water penetration and the viscosity is a characteristic indicator for the gel structure, the degree of swelling and the drug release rate.     

烟酸缓释骨架片的制备及体外释放度考察

目的 :制备烟酸缓释骨架片并考察其体外释放度。方法 :以国外上市 Niaspan R○ 作为对照 ,考察了 4种型号的羟丙基甲基纤维素 (HPMC)对释放性能的影响 ,并比较了缓释片在水、0 .1mol/ L 盐酸及 p H6 .8磷酸盐缓冲液三种介质中的释放度。结果 :用 Higuchi方程拟合发现 ,自制片和对照片均具有典型的缓释性能 ,而且自制片和对照片的释放度没有差别。结论 :自制的烟酸缓释骨架片工艺简单易行 ,释放度亦符合要求。     

Influence of hydrogel structure on the processes of water penetration and drug release from mixed hydroxypropylmethyl cellulose/thermally pregelatinized waxy maize starch hydrophilic matrices

The kinetics of water penetration and molsidomine release from both hydroxypropylmethyl cellulose (HPMC) and mixed HPMC/thermally pregelatinized waxy maize starch (SDWMT) hydrophilic matrices has been examined in 0.1 mol x dm(-3) HCl (pH 1.0) and 0.06 mol x dm(-3) Na3PO4/HCl buffer (pH 6.8). The rheological oscillatory test parameters of their gel layers obtained by swelling of the matrices in the two aqueous media have been observed. The kinetic swelling properties of mixed HPMC/SDWMT hydrogels (i.e. degree and velocity of both water penetration and swelling, transport mechanism which controls solvent sorption) directly influence the drug release behaviour and the structural features of the formed gel layer. Both diffusion processes are diffusion-controlled ones, their mechanisms being influenced insignificantly by the relaxation properties of the hydrated macromolecules. It has been established by means of comparative viscoelastic analysis, that mixed HPMC/SDWMT hydrogels demonstrate the typical behaviour of 'filled' composite systems having poor adhesion between the surface of the elastic SDWMT 'filler' and the continuous HPMC phase. Due to the inter-phase relations between the swollen starch granules and the linear cellulose derivative as well as to the specific structure of amylopectin molecule, the pregelatinized waxy maize starch shows a stronger influence on the velocities of both water penetration and drug release from mixed HPMC/SDWMT matrices.     

Characterization of Indomethacin Release from Polyethylene Glycol Tablet Fabricated With Mold Technique

The purpose of this study was to use polyethylene glycol as a carrier to improve the solubility of an aqueous insoluble drug by melting and molding method. The release of dissolved drug was designed to be subsequently sustained with an addition of xanthan gum. The release of indomethacin from the developed system into phosphate buffer pH 6.2 was conducted using the dissolution apparatus. This carrier system could effectively enhance the solubility of indomethacin and an addition of xanthan gum could sustain the drug release. Eudragit L100 film coating could protect the carrier not to be disturbed with HCl buffer pH 1.2 and could dissolve in phosphate buffer pH 6.2, therefore, the drug release from coated tablet was initially very low but subsequently gradually released and prolonged in phosphate buffer pH 6.2. Differential scanning calorimetry study indicated the amorphous state of drug in polyethylene glycol carrier. Scanning electron microscopy photomicrograph indicated the drug diffusion outward through the porous network of matrix tablets into the dissolution fluid and curve fitting signified that the drug release kinetic was Fickian diffusion.     

Use of natural gums and cellulose derivatives in production of sustained release metoprolol tablets

Metoprolol tartrate sustained-release tablets (100 mg) were prepared using xanthan/guar gums and also hydroxypropyl methyl cellulose (HPMC) carboxymethyl-Cellulose (CMC) polymers by direct compression method. Physical characteristics of the tablets and water uptake in addition to their dissolution profiles were compared with standard (Lopressor® SR) tablets. Dissolution test was performed in the phosphate buffer solution (pH 6.8) and the samples were analyzed spectrophotometerically in 275.7 nm. Dissolution studies showed that formulations containing 100 and 80% of HPMC, 100% of guar, and 20% of xanthan followed the Higuchi model, while those containing 60 and 40% HPMC and 100 and 80% xanthan followed a zero-order model. The tablets with 40% xanthen followed a Hixon-Crowell model. In cellulose derivatives the highest MDT and dissolution efficiency until 8 hr (DE₈%) belonged to tablets with 40% HPMC, increasing the amount of CMC decreased the drug release rate, and formulations containing 60 and 40% of HPMC had the USP dissolution standards. While, in the gum formulations, the highest mean dissolution time and the lowest DE₈% belonged to tablets with 100% xanthan, increasing the xanthan decreased the release rate of metoprolol, and formulations containing 80 and 100% xanthan had the USP dissolution standards. Results showed that natural gums are suitable for production of sustained-release tablets of metoprolol.     

Effect of anionic polymers on the release of propranolol hydrochloride from matrix tablets.

Anionic polymers, namely Eudragit S, Eudragit L 100-55, and sodium carboxymethylcellulose, were incorporated into hydroxypropylmethylcellulose (HPMC K100M) to modify the drug release from HPMC matrices. The effects of changing the ratio of HPMC to anionic polymers were examined in water and in media with different pH. The dissolution profiles were compared according to release rates. The interaction between propranolol hydrochloride and anionic polymers was confirmed using the UV difference spectra method. The drug release was controlled with the type of anionic polymer and the interaction between propranolol hydrochloride and anionic polymers. The HPMC-anionic polymer ratio also influenced the drug release. The matrix containing HPMC-Eudragit L 100-55 (1:1 ratio) produced pH-independent extended-release tablets in water, 0.1 N HCl, and pH 6.8 phosphate buffer.     

Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression

The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8–12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression.