乙酰螺旋霉素片的工艺研究

目的：筛选乙酰螺旋霉素片最佳处方。方法：考察预胶化淀粉、低取代羟丙基纤维素和吐温－８０对乙酰螺旋霉素片的质量影响,并与２种市售乙酰螺旋霉素片作溶出度比较。结果：筛选的最佳处方制备的乙酰螺旋霉素片,体外溶出度大为提高。结论：本法处方合理,工艺简单,适用于工业化生产。     

用球形结晶法提高甲苯磺丁脲的溶出速率

甲苯磺丁脲球晶的制备:试验选用的附加剂有HPMC(羟丙基甲基纤维素)、POE 40(聚氧乙烯单硬脂酸酯40)、HCO(氢化蓖麻油)和CMC(羧甲基纤维素),在水溶液中的浓度为0.01、0.04、0.1、0.4和2%。先将20%甲苯磺丁脲的NaOH溶液25 ml和附加剂水溶液250ml置500ml烧杯内混匀,再在600rpm搅拌下加1MHCl中和并使甲苯磺丁脲结晶,然后以每分钟10ml速度加入适量乙醚使结晶聚集,在25°±1℃继续搅拌40分钟即可。甲苯磺丁脲球晶的颗粒大小和溶出速率:附加剂浓度为0.04～2%可得到直径为     

提高灰黄霉素片溶出度的处方工艺改进

以玉米淀粉为稀释剂,低取代羟丙基纤维素为崩解剂,采用羧甲基纤维素钠水溶液为粘合剂,制成的灰黄霉素片快速崩解和溶出,溶出度增大.     

提高灰黄霉素片溶出度的处方工艺改进

以玉米淀粉为稀释剂,低取代羟丙基纤维素为崩解剂,采用羧甲基纤维素钠水溶液为粘合剂 ,制成的灰黄霉素片快速崩解和溶出,溶出度增大.     

提高灰黄霉素片溶出度的处方工艺改进

以玉米淀粉为稀释剂,低取代羟丙基纤维素为崩解剂,采用羧甲基纤维钠水溶液为粘合剂,制成的灰黄霉素片快速崩解和溶出,溶出度增大。     

卡马西平片剂的药剂学研究概况

目的：阐述卡马西平片剂的药剂学研究概况。方法：查阅文献，综述了卡马西平片剂的处方研究、工艺研究、溶出度和药动学特点。结果：论述了配方中的羟丙基甲基纤维素（HPMC）、低取代羟丙基纤维素（L-HPC）、β-环糊精、聚山梨醇酯-80以及主药的粒度、压力对卡马西平溶出度及生物利用度的影响，并总结影响其疗效的主要因素。结论：卡马西平的水溶性和吸收的多峰现象是影响卡马西平片剂疗效的关键因素。     

倍他环糊精卡马西平分散片溶出试验

采用倍他环糊精包合技术及低取代羟丙基纤维素为崩解剂 ,将卡马西平制成分散片 ;结果显示 :由包合物制成的分散片的溶出度比卡马西平普通片显著增加 ,90 %药物在 3min内溶出。     

非那雄胺包衣分散片的制备及体外溶出度测定

目的优化非那雄胺分散片的处方及制备工艺,测定其溶出度。方法采用湿法制粒压片,正交试验优化处方工艺。结果非那雄胺片的处方组成：稀释剂为40%微晶纤维素和50%乳糖,崩解剂为5%低取代羟丙基纤维素,黏合剂为5%聚维酮K3025%的乙醇溶液,包衣液为15%的85G型欧巴代,45 min时溶出度可达90%以上。结论自制非那雄胺片质量稳定,工艺可靠,适合工业化生产要求。     

改善乙酰水杨酸片溶出度的研究

采用干法制粒制备乙酰水杨酸片，分别加入低取代－羟丙基纤维素（Ｌ５－ＨＰＣ）、羧甲基淀粉钠（ＣＭＳ－Ｎａ）及干淀粉作崩解剂［１］，以改善溶出度。实验表明，内加ＣＭＳ－Ｎａ及干淀粉，干法制粒压片，能够明显改善乙酰水杨酸片的溶出度。     

阿替洛尔片制剂工艺的研究

目的研究阿替洛尔片中粘合剂淀粉浆最佳使用浓度;辅料低取代羟丙基纤维素（L-HPC）、吐温-80最佳使用量。方法以阿替洛尔片溶出度为考察指标,采用正交实验法,以低取代羟丙基纤维素（L-HPC）使用量（A）、吐温-80使用量（B）、淀粉浆浓度（C）3个因素．每个因素选取3个水平进行实验,所制定的因素水平选用b（3^4）正交表来安排试验,最后确定制剂工艺。结果各因素对阿替洛尔溶出度的影响大小分别A〉B〉C。结论最佳工艺条件应为A3B3C1,即低取代控丙基纤维素（L-HPC）使用量9％,吐温-80使用量0．1596,淀粉浆浓度5％。     

Enhancement of the dissolution rate of a poorly water-soluble drug (tolbutamide) by a spray-drying solvent deposition method and disintegrants

The dissolution rate of a poorly water-soluble drug, tolbutamide, was improved by spray-drying a diluted ammonia solution of the drug containing either a low-substituted hydroxypropylcellulose (L-HPC) or partly pregelatinized corn starch (PCS) as disintegrants. With L-HPC the resultant particles were agglomerates of disintegrant with drug on the surface and within the particles, while particles formed with PCS were composed of a single core of PCS on which the drug was deposited. The deposited drug crystals were very fine because the rapid solvent evaporation restricted crystal growth. The spray-dried particles prepared with PCS had a structure similar to that of an ordered mix. The drug dissolution rate from the spray-dried particles was more rapid than that of the powdered drug alone or with disintegrant and could be attributed to separation of the layer of fine drug crystals from the surface of the particles by swelling of disintegrant. PCS enhanced the drug dissolution rate compared with systems using corn starch. The dissolution rate also depended on the drug content of the particles which was higher than that in ordered mixtures or conventional solvent deposition systems. This system described also had the advantage of avoiding the use of organic solvents.     

Changed crystallinity of mebendazole solid dispersion: improved anthelmintic activity

To improve the efficacy of mebendazole (MBZ), a poorly water-soluble drug, MBZ solid dispersions containing different proportions of low-substituted hydroxypropylcellulose (L-HPC) were prepared by lyophilization process. The physical characteristics of recrystallized MBZ, and solid dispersions (SD) at different MBZ:L-HPC proportions were investigated in terms of morphology (scanning electron microscopy, SEM), powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution rate. The in vivo performance was assessed by anthelmintic activity studies against enteral (pre-adult) stage of Trichinella spiralis in mice. The XRD, DSC and SEM revealed a characteristic decrease in crystallinity when increasing the L-HPC proportions in the solid dispersions. The dissolution studies demonstrated a marked increase in the dissolution rate in comparison with recrystallized drug. The considerable improvement in the dissolution rate of MBZ from solid dispersions was attributed to decreased drug crystallinity and altered surface morphology (major) and to the wetting effect of L-HPC (minor). The in vivo studies revealed that the anthelmintic effects of solid dispersions in mice were significantly increased in comparison with recrystallized MBZ (1.74-fold for SD-1:1, 3.20-fold for SD-1:2.5 and 3.80-fold for SD-1:5). These results have shown the suitability of MBZ:L-HPC solid dispersions for the treatment of enteral helmintic diseases at low doses.     

L-HPC对提高盐酸小檗碱片溶出度的影响

采用低取代羟丙纤维素(L-HPC)、淀粉为辅料,以不同配比及工艺制备盐酸小檗碱片,考察L-HPC对释药的作用.结果表明在制粒前后加入4.0%L-HPC制得的盐酸小檗碱片10min的溶出度即达90%以上.     

Dissolution properties and bioavailability of ground mixture of N,N-dimethylcarbamoylmethyl alpha, 2-dimethyl-5H-[1]benzopyrano[2,3-b]-pyridine-7-acetate with various pharmaceutical ingredients

Ground mixture of N,N-dimethylcarbamoylmethyl alpha, 2-dimethyl-5H-[1]benzopyrano-[2,3-b]pyridine-7-acetate (1) with various pharmaceutical ingredients were prepared in order to investigate their dissolution behaviors and bioavailability. Taking into account the weakly basic property of 1, the dissolution rate was determined in the 2nd fluid (pH 6.8) of disintegration test, JP XI. Dissolution rates of the ground mixtures (1 : 1, w/w) of 1 with hydroxypropylcellulose-L (HPC-L), low substituted hydroxypropylcellulose (L-HPC) or lactose respectively, showed a significant increase compared with compound 1 alone. Three kinds of experimental fine granules were prepared; type A: produced from ground mixture of 1, HPC-L, L-HPC and lactose; type B: produced from physical mixture having the same composition as type A; type C: produced 1, L-HPC and lactose. In these fine granules, only type A exhibited pH-independent dissolution profiles. Bioavailability study was carried out in beagle dogs whose gastric acidity was controlled in advance to low levels by administration of omeprazole. The test was conducted in a cross over design. Reflecting their dissolution characteristics, type A granules showed better bioavailability than the others. These results suggest that grinding is useful for the improvement of the dissolution property and bioavailability of 1, a weakly basic compound.     

阿维A胶囊处方筛选及稳定性研究

目的:筛选阿维A胶囊的最佳处方、工艺,并考察其成品的稳定性。方法:以可压性淀粉、乳糖、低取代羟丙基纤维素(L-HPC)处方用量为考察因素进行正交试验,以溶出度、流动性、含量均匀度等为成品质量考察指标进行综合评价;在光照、高温、高湿条件下对成品进行稳定性考察。结果:最佳处方组成为可压性淀粉20%、乳糖20%、L-HPC1%,采用制粒工艺制备;所得成品质量稳定。结论:优选的阿维A胶囊处方、工艺合理,由其制备的成品溶出度、含量均匀度、稳定性等均达《中国药典》要求。     

Particle design of tolbutamide in the presence of soluble polymer or surfactant by the spherical crystallization technique: improvement of dissolution rate

Poorly soluble crystals of tolbutamide were modified in the presence of a soluble polymer or surfactant by the spherical crystallization technique, the objective being to improve the dissolution rate and to transform platelet crystals into spherical agglomerates. An HCI solution was added to a tolbutamide:NaOH solution containing a water-soluble polymer or surfactant. The tolbutamide crystals were agglomerated with either and were free flowing and spherically compact. The size of the crystals of the agglomerate depended on the viscosity of the solvent and adsorption of the surfactant onto the crystal surface. The tolbutamide-agglomerated crystals dissolved isotropically, with no evidence of disintegration. The dissolution process was described in terms of the Hixson-Crowell equation. The dissolution rate of the agglomerate was 8 times faster than that of conventionally crystallized tolbutamide. Therefore, the solubility and flow-ability of tolbutamide can be improved using the spherical crystallization technique.     

乙酰螺旋霉素片的制备工艺及对溶出度的影响

目的:寻求制备乙酰螺旋霉素片的最佳工艺。方法:考察L—HPC的用量和加入方法、粘合剂种类、乙酰螺旋霉素粉末粒度及润滑剂对乙酰螺旋霉素片溶出度的影响。结果:所选处方和工艺制备的乙酰螺旋霉素片,硬度较好,外观光洁,溶出度可达98％以上。结论:本法处方合理,工艺简单,适用于工业化生产。     

Influence of surfactants (present in the dissolution media) on the release behaviour of tolbutamide from its inclusion complex with beta-cyclodextrin.

The possible competitive displacement of a drug from its cyclodextrin-based inclusion complex by a third substance was investigated by studying the dissolution behaviour of tolbutamide-beta-cyclodextrin inclusion complex in demineralised water and in aqueous solution of different surfactants. Physical mixtures and kneaded systems were prepared in 1:1 and 1:2 drug-beta-cyclodextrin mol/mol ratios and they were characterised by hot-stage microscopy, differential scanning calorimetry, and X-ray powder diffractometry. The release behaviour of tolbutamide from its inclusion complex was studied by studying the dissolution of the binary systems in water and in aqueous solutions of three surfactants: polysorbate 20, poloxyl 23-lauryl ether, and sodium lauryl sulphate. When demineralised water was used as the dissolution media, the fastest dissolution of tolbutamide was obtained from 1:2 kneaded system followed by 1:1 kneaded system. The presence of poloxyl 23-lauryl ether and sodium lauryl sulphate in the media caused a decrement in the rate and extent of dissolution of the drug from both kneaded systems in comparison with that obtained from the same systems in water. However, the release of tolbutamide from the kneaded systems remains unaffected when polysorbate 20 was present in the dissolution media. Results of this study suggest that the simultaneous presence of beta-cyclodextrin and surfactants of proper molecular structure in a pharmaceutical formulation can give rise to an unexpected dissolution of the drug.     

Influence of different types of low substituted hydroxypropyl cellulose on tableting,disintegration, and floating behaviour of floating drug delivery systems

The object of the present study is to evaluate the effect of application of low-substituted hydroxypropyl cellulose (L-HPC) 11 and B1 as excipients promoting floating in gastroretentive tablets. Directly compressed tablets were formed based on experimental design. Face-centred central composite design was applied with two factors and 3 levels, where amount of sodium alginate (X₁) and L-HPC (X₂) were the numerical factors. Applied types of L-HPCs and their 1:1 mixture were included in a categorical factor (X₃). Studied parameters were floating lag time, floating time, floating force, swelling behaviour of tablets and dissolution of paracetamol, which was used as a model active substance. Due to their physical character, L-HPCs had different water uptake and flowability. Lower flowability and lower water uptake was observed after 60 min at L-HPC 11 compared to L-HPC B1. Shorter floating times were detected at L-HPC 11 and L-HPC mixtures with 0.5% content of sodium alginate, whereas alginate was the only significant factor. Evaluating results of drug release and swelling studies on floating tablets revealed correlation, which can serve to help to understand the mechanism of action of L-HPCs in the field development of gastroretentive dosage forms.     

用球形结晶技术改善甲苯磺丁脲的溶出速率

用球形结晶技术将难溶性药物甲苯磺丁脲在羧甲基纤维素钠(CMC—Na)的溶液中制成球形结晶聚集体(简称球晶)。用扫描电镜法观察到原药结晶为棱状结晶,而球形结晶为小片状及小梭状结晶的聚集体。用粉末X线衍射谱检测了球晶与原晶,发现衍射峰有不同之处,说明有部分晶型发生改变。其球晶的溶解过程由Hixson—Crowll方程式描述,溶解比原药快。