一些常用片剂填充剂与崩解剂的性能比较

以碳酸钙为模型药物 ,以抗张强度、崩解时间为指标比较了 4种填充剂 (玉米淀粉、糊精、微晶纤维素、可压性淀粉 )的压缩成形性及 8种崩解剂 (微晶纤维素PH3 0 1、PH3 0 2、可压性淀粉、交联羧甲基纤维素钠、交联聚乙稀吡咯烷酮、干淀粉、羧甲基纤维素钙、低取代羟丙基纤维素 )的崩解性。结果表明 ,可压性淀粉的压缩成形性优于其他 3种填充剂 ,占主药量 5 %时的抗张强度达到1 62MPa,此时糊精、微晶纤维素、玉米淀粉的抗张强度分别为 1 4 6MPa、1 1 6MPa、0 65MPa;吸水膨胀性较强的交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠、干淀粉及羧甲基纤维素钙的崩解效果较好 ,采用不同填充剂时的崩解时限均在 2min内     

The effect of some binding agents on the mechanical properties of granules and their compression characteristics

The modulus of elasticity and the crushing strength of cylindrical granules prepared by a template method, and the friability of conventional granules were measured and the effect of the binding agents, PVP, methyl cellulose and maize starch examined. These properties were related to the compression characteristics of the granules and to the crushing force of the subsequent tablets. According to the base material two cases were observed. With dicalcium phosphate little plastic flow was evident and low radial stress transmission was noticed, the softest granules led to the weakest compacts. With paracetamol more plastic flow occurred giving a greater axial to radial conversion of force and the softest granules produced the strongest tablets. The extent of further generated contact area played the major role. Generally, due to the better bonding capacity, dicalcium phosphate gave stronger compacts than paracetamol, although lower radial transmission ratios were recorded. A good conversion of axial to radial force was thus proved not to be the main factor in obtaining good tablets, as was also confirmed by the paracetamol powder alone. With paracetamol the residual pressure on the die wall was greater with the formulations producing satisfactory tablets than with paracetamol alone which gave rise to capping.     

Formulation and Evaluation of Alstonia boonei Stem Bark Powder Tablets

The aim of this work was to formulate Alstonia boonei dried stem bark powder into tablets by wet granulation method using acacia, gelatine and sodium carboxymethyl cellulose as binders at concentrations of 1, 2, 4 and 8% w/w. The phytochemistry of the stem bark of Alstonia boonei was evaluated. The micromeritic properties of the granules prepared were studied. The tablets were evaluated using the necessary official and unofficial tests. The results of the phytochemical analysis showed that alkaloids, tannins, steroids, saponins, glycosides, flavonoids and terpenoids were present while anthroquinones and acidcompounds were absent. Micromeritic studies showed that Alstonia boonei granules had good flowability. The formulated tablets complied with British Pharmacopoeial specification for weight uniformity, hardness (≥5 kgf) and tablet friability (<1%). For disintegration test, tablets formulated with gelatine and acacia at concentrations of 1, 2 and 4% w/w complied with Pharmacopoeial specification. However, tablets formulated with SCMC (1-8% w/w) and 8% w/w of acacia and gelatine failed the disintegration tests (Disintegration time more than 15 min).     

氯雷他定片的制备及质量控制

目的:制备氯雷他定片并建立其质量控制方法。方法:将氯雷他定与十二烷基硫酸钠、淀粉、微晶纤维素等辅料混合制备片剂。采用紫外分光光度法测定氯雷他定含量。结果:氯雷他定检测浓度线性范围为4~28μg/ml(r=0.9 999),平均回收率为99.9%,相对标准偏差为0.3%。结论:该制剂制备工艺简单,质量控制方法可行。     

Formulation and evaluation of omeprazole tablets for duodenal ulcer

Omeprazole pellets containing mucoadhesive tablets were developed by direct punch method. Three mucoadhesive polymers namely hydroxypropylemethylcellulose K4M, sodium carboxy methylcellulose, carbopol-934P and ethyl cellulose were used for preparation of tablets which intended for prolong action may be due to the attachment with intestinal mucosa for relief from active duodenal ulcer. Mucoadhesive tablets were coated with respective polymer and coated with Eudragit L100 to fabricate enteric coated tablets. The prepared tablets were evaluated for different physical parameters and dissolution study were performed in three dissolution mediums like 0.1N hydrochloric acid for 2h, pH 6.5 and pH 7.8 phosphate buffer solution for 12hr. Sodium carboxymethylcellulose showed above 95% release within 10 h where as carbopol-934P showed slow release about 88% to 92% over a period of 12 h. having excellent mucoadhesive strength but ethyl cellulose containing tablets showed less than 65% release. The release mechanism of all formulation was diffusion controlled confirmed from Higuchi's plot. Thus, the present study concluded that, carbopol-934P containing mucoadhesive tablets of omeprazole pellets can be used for local action in the ulcer disease as well as for oral controlled release drug delivery.     

D-最优混料设计优选五味金色分散片制剂处方

目的:应用D-最优混料设计优选五味金色分散片处方。方法:以片剂外观、片剂硬度和崩解分散均匀时间的综合评分为指标,考察微晶纤维素、预胶化淀粉、交联羧甲基纤维素钠的配比对片剂成型的影响,并测定了优化处方片剂释放度。结果:微晶纤维素、预胶化淀粉和交联羧甲基纤维素钠的最优处方配比为23.27％:19.36％:7.37％;释放速度高于胶囊剂。结论:优化处方具有良好的分散片制剂学特定,重复性好;D-最优混料设计用于分散片处方优化效果较佳。     

甲磺酸培氟沙星分散片的处方研究和体外溶出度考察

目的:优选甲磺酸培氟沙星分散片处方并考察其体外溶出度。方法:对处方中选用的微晶纤维素、交联聚乙烯吡咯烷酮、羧甲基淀粉钠和聚乙烯吡咯烷酮用量进行正交试验;采用紫外分光光度法考察甲磺酸培氟沙星分散片与普通片的溶出度。结果:优选的最佳处方为微晶纤维素20%、交联聚乙烯吡咯烷酮6%、羧甲基淀粉钠5.5%和聚乙烯吡咯烷酮8%。所制分散片在30s内完全崩解,15min时溶出度明显高于普通片。结论:采用本处方及工艺制得的甲磺酸培氟沙星分散片质量可靠,崩解时限短,体外释放度优于普通片。     

Compatibility study between acetylcysteine and some commonly used tablet excipients.

Differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FT-IR), HPLC and TLC were used to investigate the interactions between the mucolytic drug acetylcysteine and a number of commonly used tablet and capsule excipients. Acetylcysteine was found to be compatible with microcrystalline cellulose (Avicel PH 101), sodium carboxymethylcellulose, amorphous silicon dioxide (Aerosil), PVP, cross-linked PVP (Polyplasdone XL), corn starch, saccharose and magnesium stearate. Acetylcysteine thermal stability (onset degradation temperature) was decreased in mixtures with corn starch, magnesium stearate, saccharose and lactose. Interactions of acetylcysteine with lactose, PEG 4000 and 6000, glycine, adipic acid and saccharin sodium were found using DSC and studied in detail with FT-IR, HPLC and TLC. The results suggest that acetylcysteine in mixtures with PEG 4000, glycine or saccharin sodium is degraded during storage at conditions of high temperature and humidity.     

头孢泊肟酯分散片的制备及溶出度测定

目的制备头孢泊肟酯分散片并建立其溶出度测定方法。方法以可压性、崩解时限、分散均匀性、溶出度为主要评价指标确定最终最佳处方;采用中国药典2005年版二部附录ΧC溶出度测定第一法,以0.05 mol.L^-1盐酸为溶出介质,转速为100 r.min-1,在第30 min取样,264 nm波长处测定其溶出度。结果最终处方为头孢泊肟酯43.3%,羧甲基淀粉钠21.7%,微晶纤维素10%,羟丙基纤维素10%,交联聚维酮4.33%,十二烷基硫酸钠0.67%,微粉硅胶5%,阿斯巴甜3.33%,桔子香精1.67%。头孢泊肟酯溶出度检测浓度的线性范围为6.25-31.25μg.mL-1（r2=0.999 6）;平均回收率为99.66%,RSD=0.5%（n=9）,6批样品30 min溶出度均＆gt;85%。与日本三共株式会社生产的头孢泊肟酯片相比,分散片前30 min的溶出速度快于普通片剂。结论头孢泊肟酯分散片制备工艺简单;溶出度测定方法操作简便、结果准确。     

卡络磺钠片的处方工艺研究

目的优选卡络磺钠片的处方工艺。方法以单因素试验筛选填充剂、黏合剂和崩解剂,正交试验优化主要辅料用量,湿法制粒制备卡络磺钠片。结果优化后的处方为每片含卡络磺钠10 mg、淀粉20 mg、乳糖20 mg、微晶纤维素60 mg、羟丙甲纤维素5 mg、交联聚维酮4 mg、硬脂酸镁1 mg。优化后的工艺为,将淀粉于100℃干燥成含水量5%～8%的干淀粉,与卡络磺钠等量递加混合,粉碎,过筛;再与乳糖、微晶纤维素、羟丙甲纤维素、内加交联聚维酮混合,过筛;加乙醇适量,16目筛制粒2次,湿颗粒60℃左右干燥,14目筛整粒,外加交联聚维酮和硬脂酸镁,混合,压片。结论本处方工艺制备的卡络磺钠片,质量检查符合要求,溶出度较市售卡络磺钠片高,达到了设计要求。     

Oxytetracycline tablet formulations: the influence of excipients and the method of granulation.

The proportion of microcrystalline cellulose and alginic acid present as excipients in the dry mix for an oxytetracycline dihydrate tablet formulation, prepared by a conventional wet granulation process, has been shown to influence granule formation and properties. Granule size distributions have varied widely due perhaps to variation in binder distribution. Granulating with water was equally satisfactory to granulating with a PVP solution. Slugged granules produced robust tablets, which disintegrated and dissolved rapidly.     

盐酸替扎尼定口腔黏附片的研制及质量评价

目的制备盐酸替扎尼定口腔黏附片并评价其质量。方法采用不同配比的羟丙甲基纤维素(HPMC)、羧甲基纤维素钠(SCMC)、β-环糊精和羟丙基-β-环糊精等辅料,用直接压片法压片制备盐酸替扎尼定口腔黏附片,并对黏附片的理化性质、药物含量、药物体外释放度和黏附力进行评价。结果得到各项指标均较适宜的处方:盐酸替扎尼定4.56mg,羟丙甲纤维素20mg,羧甲基纤维素钠75mg,羟丙基-β-环糊精27.36mg,甘露醇4mg,阿斯巴甜1mg,微粉硅胶1mg。结论成功制备了盐酸替扎尼定口腔黏附片,可用于进一步的体内、体外研究。     

无时滞非达霉素肠溶片的制备及溶出评价

目的: 制备无时滞非达霉素肠溶片,考察其溶出特性。方法: 采用湿法制粒工艺,通过正交实验进行片芯优化,以甲基丙烯酸与丙烯酸乙酯共聚物为肠溶包衣材料,制备非达霉素肠溶片,以体外释放度为指标,考察其溶出行为。结果: 片芯中羟丙甲纤维素和交联羧甲基纤维素钠的用量分别为1.2%和4.5%,微晶纤维素和淀粉的比例为3:1,肠溶层共聚物的比例为50%时,制备的非达霉素肠溶片在pH1.0盐酸中2h释放度小于10%,在pH4.5醋酸盐缓冲液中可以崩解释放,在pH6.8磷酸盐缓冲液中快速释放,10min释放度大于60%。结论: 制备的非达霉素肠溶片与普通肠溶片相比无时滞效应,有望进行工业化生产。     

Development and evaluation of fast-dissolving tablets of meloxicam-β-cyclodextrin complex prepared by direct compression

The aim of this study was to prepare fast-dissolving tablets of meloxicam after its complexation with β-cyclodextrin (β-CD) and to investigate the effect of using different superdisintegrants on the disintegration and release of meloxicam from the tablets. A complex of meloxicam with β-CD was prepared by spray drying and then compressed in the form of tablets utilizing the direct compression technique. Three superdisintegrants were employed at various levels - sodium starch glycolate, croscarmellose sodium, and crospovidone. Co-spray dried micro-crystalline cellulose and mannitol (Avicel HFE-102) were used as diluents in the tablets. Prior to compression, the pre-compression parameters showed satisfactory flow properties. Post-compression parameters showed that all tablet formulations had acceptable mechanical properties. Wetting and disintegration times were prolonged by increasing the level of sodium starch glycolate in the tablets. This was attributed to the formation of a viscous gel layer around the tablets by sodium starch glycolate whereas this effect was not observed with croscarmellose sodium and crospovidone. Dissolution studies showed fast release of meloxicam except in tablets containing a high level of sodium starch glycolate. Complexation of meloxicam with β-CD significantly improved the solubility of the drug and improved the mechanical properties of tablets produced by direct compression.     

A Comparative Study of Controlled Release Matrix Tablets of Diclofenac Sodium,Ciprofloxacin Hydrochloride,and Theophylline

The need for controlled release formulations for diclofenac sodium, ciprofloxacin, and theophylline is well recognized. In our study, controlled release tablets of the three drugs were formulated by the matrix-embedding technique using ethyl cellulose as retardant. Tablets of all the drugs were of good physical quality with respect to appearance, drug content uniformity, hardness, weight variation, and friability. In vitro release rate studies showed that ethyl cellulose extended the release of the three drugs to 12 hr or more. Release patterns from formulations of the three drugs followed Higuchi's square root kinetics. At pH 6.8, the release rate was higher in all three drugs, probably due to increased solubility of the drugs and/or increased swelling of ethyl cellulose at the higher pH. The formulations were highly stable and possessed reproducible release kinetics across batches.     

A comparative study of controlled release matrix tablets of diclofenac sodium, ciprofloxacin hydrochloride, and theophylline

The need for controlled release formulations for diclofenac sodium, ciprofloxacin, and theophylline is well recognized. In our study, controlled release tablets of the three drugs were formulated by the matrix-embedding technique using ethyl cellulose as retardant. Tablets of all the drugs were of good physical quality with respect to appearance, drug content uniformity, hardness, weight variation, and friability. In vitro release rate studies showed that ethyl cellulose extended the release of the three drugs to 12 hr or more. Release patterns from formulations of the three drugs followed Higuchi's square root kinetics. At pH 6.8, the release rate was higher in all three drugs, probably due to increased solubility of the drugs and/or increased swelling of ethyl cellulose at the higher pH. The formulations were highly stable and possessed reproducible release kinetics across batches.     

Formulation and Evaluation of Cefixime Trihydrate Matrix Tablets Using HPMC,Sodium CMC,Ethyl Cellulose

The objective of the present work is to design sustained release matrix tablets of cefixime trihydrate by incorporating drug in a matrix made up of release retardant polymers, which prolong drug release leading to minimization of the peak and valley effect in the plasma and provide patient convenience. The effect of combination of polymers on parameters like release pattern, release mechanism of the drug were studied. Total nine formulations each containing 200 mg of drug were prepared by direct compression method. The formulations F-1, F-2, F-3 were prepared with a 1:1 drug to polymer ratio using hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose. F-4 was prepared with a 1:1 ratio of hydroxypropyl methylcellulose, carboxymethyl cellulose sodium, F-5 as prepared with a 1:1 ratio of hydroxypropyl methylcellulose and ethyl cellulose, F-6 was prepared with a 1:1 ratio of carboxymethyl cellulose sodium and ethyl cellulose, F-7, F-8, F-9 were prepared by using polymers hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose in the ratios of 0.5:0.5:1, 0.5:1:0.5, and 1:0.5:0.5. Designed matrix tablets were evaluated for various pre-compression and post-compression parameters. Formulation F-5 showed 102.15 % release at the end of 12 h and it is selected as the best formulation. All Formulations followed zero order with non-Fickian diffusion method.     

氯氮平口腔崩解片的制备及质量控制

目的制备氯氮平口腔崩解片并探讨其质量控制。方法考察填充剂微晶纤维素、甘露醇及崩解剂交联羧甲基纤维素钠的用量,以外观、口感及体外崩解时间为指标,通过正交试验优化处方,采用直接压片法制备口腔崩解片,并对其崩解时间、溶出度、含量进行检测。结果氯氮平口腔崩解片在30s内可完全崩解,2min溶出达90％以上,含量符合规定。结论处方设计合理,制备工艺可行,产品质量可控。     

尼群地平固体分散片的制备及体外评价

目的 制备尼群地平固体分散片.方法 采用溶剂法、熔融法制备尼群地平固体分散体,再与适当辅料混合压片制备分散片.结果 采用固体分散法制备的分散片较原料药直接制备的分散片溶出更快,且聚乙二醇(PEG)为载体制备的分散片较聚乙烯吡咯烷酮(PVP)溶出更快.结论 先制备固体分散体再制备分散片,有助于提高难溶性药物的溶出速度和程度.     

Exploration of melt granulation technique for the development of coprocessed directly compressible adjuvant containing lactose and microcrystalline cellulose

The objective of the present investigation was to prepare and evaluate lactose and microcrystalline cellulose based, directly compressible adjuvant using melt granulation technique. The percentage of polymer blend (PVP K 30 and PEG 4000; 5, 10, or 15%) and the polymer blend ratio (9:1, 1:1, or 1:9) were selected as independent variables in a 3(2) full factorial design. The lactose and microcrystalline cellulose blend (3:1) was mixed with the meltable binder on a water bath at 90 degrees C. The agglomerates were cooled to 35 degrees C and subsequently passed through 30 mesh. A batch containing 12.5% of the polymer blend containing 1:9 ratio of PVP:PEG was used for further studies. In an another 3(2) full factorial design, disintegrant (crospovidone, croscarmellose sodium, or sodium starch glycolate) and mode of addition of disintegrant (intragranular, extragranular, or combination of intragranular and extragranular) were used as independent variables. The agglomerates were evaluated for percentage fines and Carr's index. Tablets were prepared on a single-punch tablet machine, and they were evaluated for tensile strength, friability, and disintegration time. Regression analysis was carried out to evolve full and refined models. Contour plots are presented for graphical expression of the results. The use of composite index is demonstrated for the selection of an appropriate batch. The disintegration time of tablets reduced from 18 min to 6 min when 6% crospovidone was included in the product. The optimized adjuvant was characterized for particle size distribution, granular friability, Kawakita's and Kuno's equation, and dilution potential study. Turmeric, glycyrrhiza, acetaminophen, and metformin HCl were used as model drugs for the preparation of tablets. The present study underlines the fact that melt granulation technique may be adopted for the development of multifunctional directly compressible adjuvant for use in pharmaceuticals. The advantages of melt granulation technique over the classical wet granulation and spray-drying are presented.