头孢氨苄片的人体生物利用度研究

杜实验采用反相高效液相色谱法，比较了１０名健康志愿者单剂量口服自制头孢氨苄片剂０．５ｇ和等剂量的市售头孢氨苄胶胶囊的生物利用度。结果表明：二种剂型Ｔｍａｘ，Ｃｍａｘ，ＡＵＣ均无显著性差异（Ｐ＞０．０５），片剂与胶囊的相对生物利用度Ｆ＝９５．９７５％。     

比较氧氟沙星两种片剂在健康志愿者体内的药物动力学

本实验采用反相高效液相荧光分析法，比较了８名健康志愿者单剂量口服两种氧氟沙星片剂后的药物动力学和生物利用度。血药浓度经时过程用ＣＡＰＰ程序包在计算机上拟合为二房室模型，试验片的相对生物利用度Ｆ为１００．１２％，经统计分析，二种片剂的Ｔｍａｘ，Ｃｍａｘ和ＡＵＣ均无显著性差异（Ｐ＞０．０５），可认为二种片剂具有生物等效性。     

α—细辛脑在人体的生物利用度研究

本文报道α－细辛脑的人体生物利用度。１２名健康受试者单剂量用药后，ＨＰＬＣ法测定血药浓度，结果片剂和胶囊剂的绝对生物利用度仅５．５６％和２．７３％，有必要改进生产工艺和处方组成。     

三种国产尼莫地平片剂的相对生物利用度研究

９例男性健康志愿者交叉口服Ａ、Ｂ、Ｃ３种国产尼莫地平片剂１２０ｍｇ，以ＨＰＬＣ法测定其血药浓度，研究了相对生物利用度。结果表明，尼莫地平在人体内的药动学符合开放两室模型，片剂Ｂ与Ａ相比，Ｃｍａｘ有显著差异，Ｂ的相对生物利用度为９４．７６％，片剂Ｃ与Ａ相比，Ｃｍａｘ差异极显著，ＡＵＣ有显著差异，Ｃ的相对生物利用度为６１．６７％。     

感冒灵冲剂和片剂生物利用度比较

本文对含中西药复方的感冒灵冲剂和片剂在兔体内的生物利用度进行了比较。结果表明:感冒灵冲剂和片剂的峰值 Y_(max)和血药浓度曲线下面积 A 有极显著性差异(P<0.01),达峰时T_(max)有显著性差异(P<0.05),冲剂的血峰浓度和吸收量明显大于片剂,冲剂的达峰时比片剂平均提高2小时。作者认为感冒灵冲剂比片剂速效且生物利用度高。     

盐酸氨溴索胶囊和片剂的药物动力学和生物利用度比较

目的：比较盐酸氨溴索胶囊和片剂的药物动力学和生物利用度。方法：８名健康志愿者随机交叉单剂量口服９０ｍｇ盐酸氨溴索胶囊和片剂,采用ＨＰＬＣ法测定氨溴索血药浓度,对２种制剂的药-时曲线下面积（ＡＵＣ）进行方差分析和双向单侧ｔ检验。结果：胶囊和片剂体内过程符合一室开放模型,Ｃｍａｘ、Ｌｍａｘ、Ｔ１／２（Ｋｅ）和ＡＵＣ均无显著性差异。结论：盐酸氨溴索胶囊和片剂具有生物等效性,胶囊的相对生物利用度为９９．７６±１５７６％。     

口服甲苯咪唑微丸的药物动力学及生物利用度

目的：比较５ 只家兔单剂量口服甲苯咪唑微丸及片剂后的药动学与生物利用度。方法：采用ＲＰＨＰＬＣ 法测定血药浓度,３Ｐ８７ 程序计算药动学参数。结果：微丸的Ｃｍａｘ、Ｔ１／２ 、ＡＵＣ分别为６４３．４９ ｎｇ·ｍｌ－ １ 、１ ．０５ ｈ、８ １７０ ．９４ ｈ·ｎｇ·ｍｌ－１ 。结论：微丸与片剂的ＡＵＣ有统计学显著性差异（ Ｐ＜０ ．０５）,相对生物利用度为５２８ ．６０ ％ 。     

盐酸曲普利啶胶囊人体失物利用度研究

目的：研究盐酸曲普利啶胶囊在正常人体的相对生物利用度。方法：采用反相高效液相色谱法测定１０名志愿者单剂量口服５ｍｇ盐酸曲普利啶胶囊和片剂后的血药浓度,计算二者的药动学参数及相对生物利用度。以Ｃｍａｘ、ＡＵＣ０等为指标,用双单侧Ｔ检验法及（１２ａ）置信区间法分析两种制剂的生物等效性。结果：二者药时曲线用一室模型拟合,统计结果表明,Ｃｍａｘ等春数无显著性差异（Ｐ＞０．０５）。结论：盐酸曲普利啶胶囊与片剂生物等效,胶囊的生物利用度为９８．２８±５．４３％。     

国产格列齐特片剂的生物利用度比较

目的：研究不同厂家生产的两种格列特剂在健康人体内的药物动力学和相对生物利用度。方法：采用ＨＰＬＣ测定１０名志愿者单剂量ｐｏ ８０ｍｇ格列齐特片剂后的血药浓度变化情况。结果：两种片剂的药物动力学参数：Ｃｍａｘ分别为５．１０和３．９７μｇ／ｍｌ，ｔｍａｘ分别３．５５和３．９７ｈ；ＡＵＣ分别８７．９７和９２．４４（ｈ．μｇ）／ｍｌ，Ｔ１／２分别为１０．７４和１０．７６ｈ。经统计学处理表明，两种片剂的ＡＵ     

盐酸异丙嗪栓的研制及其家兔体内生物药剂学评价

本文报告了盐酸异丙嗪栓剂的研究及其与片剂在家兔体内生物利用度的比较。试验采用双波长分光光度法测定盐酸异丙嗪的血药浓度。结果表明栓剂比片剂的达峰时间快，Ｔｐ之间有非常显著性差异（Ｐ〈０．０１）。Ｃｐ和ＡＵＣ没有显著性差异（Ｐ〉０．０５），栓剂的相对生物利用度为９８．０７％。     

Compression of Lactose,Glucose and Mannitol Granules

The effect of the amount of granulation liquid, compression speed and maximum compression force on the compressibility and compactibility of lactose, glucose and mannitol granules was studied. The porosity based on the geometrical shape and the uniformity of weight of tablets was also studied. Lactose and mannitol granules showed a greater compressibility than glucose granules. Mannitol granules produced the hardest tablets and lactose and glucose the weakest. The change in the amount of granulation liquid caused changes both in the granule porosity and in the amount of binder; this was attributed to differences in tablet strength. All parameters studied were relatively insensitive to changing speeds of compression in the range used, except for the breaking force of mannitol tablets, which was greatest with the lowest speed of compression. All granule masses showed a relatively good continuous flow suitable for tablet production. Tablets compressed from lactose granules had the best uniformity of weight of the tablets studied.     

Roll compaction/dry granulation: effect of raw material particle size on granule and tablet properties

The influence of particle size of MCC, as a binder, and theophylline, as an active pharmaceutical ingredient on the process of roll compaction/dry granulation was investigated using a D-optimal design of experiments. Examined parameters were particle size of both starting materials, fraction of theophylline and ribbon porosity. Therefore, different binary mixtures were roll compacted, dry granulated and compressed into tablets. Flowability of powders and granules and tensile strength of tablets made from powders or granules were the focus of this study. This study showed that a decrease in particle size of MCC or theophylline resulted in an increase of tensile strength even after roll compaction/dry granulation. Comparing tensile strength of tablets made from powder using large size MCC with ones made from granules with small sized MCC revealed that the tensile strength of tablets produced from granules was equal or even higher than tensile strength from direct compressed tablets. Furthermore, using small sized MCC instead of large sized MCC led to larger granules with better flowability. It is shown that the fraction of binder can be reduced without a loss of tensile strength of the final tablets by size reduction of MCC.     

The effect of shape and porosity on the compression behaviour and tablet forming ability of granular materials formed from microcrystalline cellulose.

The compression behaviour of two types of granules prepared from microcrystalline cellulose was evaluated. Three sets (low, intermediate and high intragranular porosity) of irregular granules and three sets of nearly spherical granules (called pellets) were prepared from microcrystalline cellulose by wet agglomeration or wet agglomeration followed by extrusion/spheronisation. The granules and pellets were similar in size. The range of intragranular porosity, although wide, was also similar for both types. The compression behaviour was evaluated in terms of the degree of compression, the appearance of the tablets and the size distribution of retrieved aggregates (after deaggregation). The compactability of the granules and pellets was also studied. Both types of granules kept their integrity during compression. The dominant mechanism during compression appeared to be permanent deformation. However, during compression of high porosity granules, fragmentation or attrition seemed to occur alongside deformation. Tablets formed from granules had a closer pore structure than those formed from pellets of equal intragranular porosity and the granules seemed to deform to a higher degree during compression. The total tablet porosity was almost independent of the intragranular porosity and the shape of the granules before compression. It is suggested that the degree of granule deformation was controlled by the intragranular porosity and voidage of each bed of granules before compression. The tensile strength of the tablets was also dependent on the porosity and the shape of the granules; tablets formed from irregular granules were stronger than those formed from pellets of an equal intragranular porosity.     

维生素E固化颗粒的制备及质量评价

分别采用不同型号的微粉硅胶或β-环糊精制备了维生素E固化颗粒,并以载药量、维生素E利用率和颗粒收率为评价指标进行筛选。结果表明,采用S80型微粉硅胶可制得载药量达60%的维生素E颗粒,明显优于β-环糊精颗粒(约6%)。用其直接粉末压片,所得片剂各项指标均符合中国药典2010年版标准。该片在高温(60℃)条件放置10 d,外观和含量未见明显变化;但在高湿[相对湿度(90±5)%、25℃]环境下片剂会吸潮,强光[(4 500±500)1x]条件下含量下降。     

Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion.

The objective of the present study was to investigate the influence of formulation factors on the physical properties of hot-melt extruded granules and compressed tablets containing wax as a thermal binder/retarding agent, and to compare the properties of granules and tablets with those prepared by a high-shear melt granulation (MG) method. Powder blends containing phenylpropanolamine hydrochloride, Precirol and various excipients were extruded in a single-screw extruder at open-end discharge conditions. The extrudates were then passed through a 14-mesh screen to form granules. The extrusion conditions and the optimum amount of wax to function as the thermal binder were dependent on the properties of the filler excipients. At the same wax level, drug release from tablets decreased in the order of using microcrystalline cellulose (MCC), lactose and Emcompress as the filler excipient. The observed differences in the dissolution properties of the tablets were due to the differences in the solubility, swellability and density of the filler excipients. Replacing Precirol with Sterotex K, a higher melting point wax, resulted in slightly increased dissolution rates, when the extrusion was performed at the same temperature conditions. Hot-melt extruded granules were observed to be less spherical than high-shear melt granules and showed lower values of bulk/tap densities. However, tablets containing MCC or lactose granules prepared by hot-melt extrusion (HME) exhibited higher hardness values. Slower drug release rates were found for tablets containing MCC by HME compared with MG. Analysis of the hot-melt extruded granules showed better drug content uniformity among granules of different size ranges compared with high-shear melt granules, resulting in a more reproducible drug release from the corresponding tablets.     

Development of manufacturing method for rapidly disintegrating oral tablets using the crystalline transition of amorphous sucrose

The industrial manufacturing of rapidly disintegrating oral tablets with a sufficient tensile strength was investigated. The manufacturing method of the tablets involved the crystalline transition of amorphous sucrose that was produced in the process of fluidized bed granulation of mannitol using sucrose solution as a binder. The aim of this article was to clarify the usefulness of amorphous sucrose formed during the granulation for the rapidly disintegrating oral tablets manufacturing, and to investigate the effects of crystalline transition of the amorphous sucrose in granules on the characteristics of the resultant tablets prepared by this crystalline transition (CT) method. The X-ray diffraction measurement and thermal analysis showed that amorphous sucrose was effectively formed in granules consisting of 95% mannitol and 5% sucrose when the granulation was performed on the condition of water content of 4%. The tensile strength of tablets comprised of the granules, which were compressed before the crystallization of amorphous sucrose, increased remarkably after storage, because new internal solid bridges were formed in the tablets as a result of the crystallization. We conclude that rapidly disintegrating oral tablets can effectively be manufactured by the CT method using the granules obtained by the fluidized bed granulation method.     

Change in porosity parameters of lactose, glucose and mannitol granules caused by low compression force

The change in porosity parameters, i.e., total pore volume, porosity percentage and pore volume size distribution of lactose, glucose and mannitol granules caused by compression with a low force was investigated. In compression, fragmentation of lactose and glucose granules increased total pore volume and porosity percentage, whereas the total pore volume and porosity percentage of mannitol granules was clearly decreased. This was due to the highly porous structure of mannitol granules, which densified easily in compression. Lactose and glucose granules were shown to resist deformation more. The pore volume size distributions of lactose and glucose tablets showed that large pores ( > 14 μm) decreased in size. For mannitol tablets, the large pores vanished and simultaneously the small granule pores ( < 14 μm) reduced in size. The features of the pore structure of granules were detected in the pore volume size distributions of compressed tablets. Mercury porosimetry, assisted by scanning electron microscopy, was shown to be an adequate method to evaluate the deformation of granules in compression.     

Gastric emptying of tablets and granules in humans, dogs, pigs, and stomach-emptying-controlled rabbits.

Rates of gastric emptying of nondigestible tablets and granules in humans were compared with those in three animal models: dogs, minipigs, and stomach-emptying-controlled rabbits. The rates of gastric emptying of both dosage forms in dogs tended to be faster than or similar to those in humans, whereas the rates in pigs were slower. In stomach-emptying-controlled rabbits, no tablets were emptied from the stomach because of their large size. The rate of gastric emptying of granules in rabbits was slow and variable. Food delayed gastric emptying in dogs, especially for tablets. In rabbits, the rate of gastric emptying of granules was faster when the granules were given before feeding, in comparison with that after feeding or under fasting conditions. We concluded that the dog is a better animal model for bioavailability studies under fasting conditions than the pig and the rabbit.     

A comparative study of the influence of alpha-lactose monohydrate particle morphology on granule and tablet properties after roll compaction/dry granulation

The influence of particle morphology and size of alpha-lactose monohydrate on dry granules and tablets was studied. Four different morphologies were investigated: Two grades of primary crystals, which differed in their particle size and structure (compact crystals vs. agglomerates). The materials were roll compacted at different specific compaction forces and changes in the particle size distribution and the specific surface area were measured. Afterwards, two fractions of granules were pressed to tablets and the tensile strength was compared to that from tablets compressed from the raw materials. The specific surface area was increased induced by roll compaction/dry granulation for all materials. At increased specific compaction forces, the materials showed sufficient size enlargement. The morphology of lactose determined the strength of direct compressed tablets. In contrast, the strength of granule tablets was leveled by the previous compression step during roll compaction/dry granulation. Thus, the tensile strength of tablets compressed directly from the powder mixtures determined whether materials exhibited a loss in tabletability after roll compaction/dry granulation or not. The granule size had only a slight influence on the strength of produced tablets. In some cases, the fraction of smaller granules showed a higher tensile strength compared to the larger fraction.     

Preparation and evaluation of taste masked orally disintegrating tablets with granules made by the wet granulation method

Using furosemide (FU) as a model drug, we examined the wet granulation method as a way to improve the taste masking and physical characteristics of orally disintegrating tablets (ODTs). In the wet granulation method, yogurt powder (YO) was used as a corrective and maltitol (MA) was used as a binding agent. The taste masked FU tablets were prepared using the direct compression method. Microcrystalline cellulose (Avicel? PH-302) and mannitol were added as excipients at a mixing ratio of 1/1 by weight. Based on the results of sensory test on taste, the prepared granules markedly improved the taste of FU, and a sufficient masking effect was obtained at the YO/FU ratio of 1 or more. Furthermore, it was found that the masking effect achieved by YO granules made with the wet granulation method was similar to or better than that produced by the granules made with dry granulation method. All types of tablets displayed sufficient hardness (over 3.5×10(-2) kN), and rapidly disintegrating tablets were obtained with YO granules produced at a mixing ratio of FU/YO=1/1, which disintegrated within 20 s. Disintegration time lengthened as the mixing ratio of YO to FU increased. In the mixing ratio of FU/YO=1/1, the hardness of tablets with granules made by the wet granulation method exceeded that of tablets with granules made by the dry granulation method, with minimal differences in disintegration time. The hardness and disintegration time of the tablets with granules made by the wet granulation method could be controlled by varying the compression force. In conclusion, YO was found to be a useful additive for masking unpleasant tastes. FU ODTs with improved taste, rapid disintegration and greater hardness could be prepared with YO-containing granules made by the wet granulation method using MA as a binding agent.