影响肝胃气痛片崩解时限的诸因素

我省1987年下半年把肝胃气痛片,按中药片剂崩解时限30s改为按西药片剂崩解时限15s。这样崩解时限超限成了肝胃气痛片合格出厂的一个障碍。下文就打片过程中的压力、崩解剂选择及用量对肝胃气片崩解时限的影响做一对比,实验如下。 1 材料与方法:主药相同,除崩解剂外其它赋型剂(润滑剂、粘合剂)相同,颗     

混料均匀设计法优化辛伐他汀口腔崩解片处方

目的优化辛伐他汀口腔崩解片处方。方法利用混料均匀设计法设计试验方案，对辛伐他汀口腔崩解片处方中的填充剂和崩解剂等主要辅料的用量进行优化。结果按照优化处方进行压片试验，辛伐他汀口腔崩解片崩解时间和脆碎度的实测值与预测值的符合性较好，且均符合要求。结论用混料均匀设计法优化后的辛伐他汀口腔崩解片的处方是可行的。     

泻粉崩解剂三种加入法对蛋氨酸片崩解时限的影响

以淀粉作崩解剂,在规格、片重、组成恒定的条件下,研究了崩解剂的内加法、外加法及内外加法对蛋氨酸片的崩解时限的影响,并以不加崩解剂作为对照。最后综合片剂的其它质量控制指标,筛选出符合新蛋氨酸片质量标准的两种制备工艺。     

淀粉崩解剂三种加入法对蛋氨酸片崩解时限的影响

以淀粉作崩解剂,在规格、片重、组成恒定的条件下,研究了崩解剂的内加法、外加法及内外加法对蛋氨酸片崩解时限的影响,并以不加崩解剂者作为对照.最后综合片剂的其它质量控制指标,筛选出符合新蛋氨酸片质量标准的两种制备工艺.     

连栀消炎片崩解剂处方筛选

目的筛选连栀消炎片崩解剂处方工艺。方法以片芯外观和崩解时限为指标,考察连栀消炎片中崩解剂种类、用量和加入方式,优选出最佳处方工艺。结果选择交联聚维酮（PVPP）作崩解剂,采用内加和外加两种方式联合使用,所得片芯外观、崩解时限均符合要求。结论筛选出的处方工艺能有效降低片芯崩解时间,符合2005年版《中华人民共和国药典》要求。     

羧甲基纤维素钙对提高中药脉络通片质量的研究

目的：采用加入崩解剂的方法，缩短脉络通片的崩解时间，提高素片硬度。方法：采取加入不同种类和浓度的崩解剂，就其硬度和崩解时限做对比性试验。结果：加入羧甲基纤维素钙5％，缩短了脉络通片崩解时限并提高了素片的硬度。结论：此方法简单，质量稳定，值得推广应用。     

红景天口腔崩解片的制备及质量控制

目的:研究红景天口腔崩解片的制备工艺,并评价其质量。方法:用直接压片法制备口腔崩解片,以崩解时限、口感等为指标采用正交设计法对崩解片中崩解剂含量、矫味剂比例进行筛选并进行处方优化;高效液相色谱法(HPLC)测定红景天苷的含量。结果:成功制备红景天口腔崩解片;根据崩解时限选用的崩解剂方案为2%低取代羟丙基纤维素(L-HPC)、10%羧甲基淀粉钠(CMS-Na)、10%交联聚维酮(PVPP);红景天与矫味剂阿斯帕坦、柠檬酸的最佳比例为41∶1∶1;口腔崩解片处方优化的结果为含35%微晶纤维素(MCC)、8%PVPP、0.5%微粉硅胶;口腔崩解片中红景天苷含量为(99.8±0.5)%。结论:红景天口腔崩解片崩解快、分布均匀、口感好、刺激小,有利于中药成分的快速溶出和方便患者服用。     

氯氮平HP-β-环糊精包合物及其口腔崩解片的制备与评价

目的制备氯氮平环糊精包合物口腔崩解片,确定其处方并进行质量评价。方法将氯氮平制成HP-β-CD包合物,正交设计法选择崩解剂、填充剂后制成口腔崩解片,考察崩解片的崩解时间、溶出度等指标,优选片剂辅料。结果氯氮平包合物包封率和载药量分别为71.12%、18.52%,以甘露醇、微晶纤维素、羧甲基淀粉钠为辅料制备的氯氮平口腔崩解片崩解时间<1 min,累积溶出度101.5%。结论选定辅料可用于制备氯氮平HP-β-CD包合物口腔崩解片,质量符合要求。     

右佐匹克隆口腔崩解片的制备及处方优化

目的:制备右佐匹克隆口腔崩解片,并优化其处方。方法:采用粉末直接压片法制备右佐匹克隆口腔崩解片,以物料休止角、崩解时限、口感评价为指标,单因素试验筛选处方中填充剂、崩解剂、润滑剂、矫味剂种类或用量;以崩解时限为指标,正交试验优化处方中填充剂比例、崩解剂用量、润滑剂用量、矫味剂用量,并考察最优处方所制右佐匹克隆口腔崩解片的硬度和主成分含量。结果:最优处方中填充剂甘露醇-微晶纤维素质量比为1∶4、崩解剂交联聚维酮用量为15%、润滑剂硬脂酸镁用量为1.0%、矫味剂甜菊苷用量为3.0%。所制3批右佐匹克隆口腔崩解片的表面光滑、口感微甜,崩解时限分别为(26.7±1.2)、(26.7±0.6)、(27.6±0.9)s,硬度分别为(3.59±0.19)、(3.49±0.18)、(3.27±0.16)kg,右佐匹克隆含量分别为(99.47±0.15)%、(99.53±0.05)%、(99.46±0.20)%,RSD均≤0.87%(n=3)。结论:所制右佐匹克隆口腔崩解片各项质量指标均符合口腔崩解片的要求。     

枸橼酸西地那非速崩舌下片的制备及质量评价

目的制备枸橼酸西地那非速崩舌下片,并评价其质量。方法采用升华剂为致孔剂,采用外加致孔刺法压制舌下片,并以真空干燥除去升华剂获得快速崩解的舌下片,对速崩舌下片以崩解时间、润湿时间、吸水比、体外溶出度等指标评价处方。结果以升华剂为致孔剂制备的枸橼酸西地那非速崩舌下片,均在30 s内崩解,且各样品均在6 min内即可达到全部溶出,其他各检测指标均符合速崩舌下片的指标。结论采用升华剂为致孔剂制备枸橼酸西地那非速崩舌下片工艺可行,制备的速崩舌下片崩解时间短,溶出速率快。     

吗啡依赖大鼠海马长时程增强改变及归元片的干预效应

目的:在体观察吗啡条件性位置偏爱(conditioned place preference,CPP)大鼠海马齿状回(dentate gyrus,DG)长时程增强(long-term potentiation,LTP)的变化,评价归元片自身有无依赖性以及对吗啡CPP和LTP的干预效应。方法:(1)连续给予吗啡(5mg·kg-1)7d,使大鼠产生明显的吗啡CPP,观察吗啡CPP的自然消退;(2)归元片(25mg·kg-1及50mg·kg-1)训练7d,d8测定大鼠对伴药箱的偏爱效应;(3)在归元片干预实验中,干预组在每次给予吗啡前15min分别给予不同剂量归元片(25、37.5mg·kg-1),观察归元片对吗啡CPP形成的影响。在以上模型的基础上,应用在体脑立体定位胞外记录技术测量海马齿状回LTP的变化。结果:(1)5mg·kg-1吗啡诱导大鼠对伴药侧产生显著性CPP;(2)归元片不能诱导大鼠形成CPP,同时也不影响DG-LTP;(3)吗啡CPP大鼠在高频刺激(high frequency stimulation,HFS)后,各时间点所记录的群体峰电位(population spikes,PS)相对幅值较对照组显著增高;(4)归元片25和37.5mg·kg-1均可拮抗吗啡CPP的获得,并能抑制吗啡对PS相对幅值的影响;(5)吗啡CPP在停用吗啡后12d消退,此时海马PS相对幅值与对照组比较无差异。结论:吗啡可诱导CPP,海马LTP在CPP形成时增强,在CPP消退后恢复正常,提示LTP参与药物成瘾过程。归元片自身不能诱导CPP,但可抑制吗啡CPP的获得与LTP的增强。     

难溶性药物新型速崩片的研究进展

摘 要难溶性药物由于其溶解度低,导致吸收差,生物利用度低,临床应用受到很大局限。运用各种增溶技术,增加难溶性药物的溶解度,进而提高其生物利用度十分必要。然而现有的增溶技术常常会造成增溶后含药量低、粘度高等问题,容易造成服用量的增大以及制剂困难。速崩片可通过局部快速释放达到提高患者顺应性以及增溶的目的。本文针对近年来出现的难溶性药物速崩片增溶技术,综述了固体分散体速崩片、包合物速崩片、乳剂冻干片、自微乳分散片、纳米混悬剂冻干片、微丸速崩片、水分散体冻干片等制剂新技术在增加难溶性药物溶解度、改善生物利用度、提高患者用药依从性等方面的应用。     

Application of some polymers in the physiocochemical design of tablet formulation.

Polyethylene glycol 4000 did not apprecialbly affect the rate of drug release from tablets. The use of sodium alginate the a tablet binder showed variable effects on the rate of drug release from the tablet i.e. The incorporation of only 2.5% of sodium alginate caused enhancement in the release rate of the drug based on its action as disintegration inducer. On the other hand, the incorporation of 20, 35 and 50% of sodium alginate showed a pronounced retardation in the rate of drug release from the tablets. This retardation was more pronounced in acid than in alkaline media. Accordingly, sodium alginate could be favourably suggested as tablet binder when retarded gastric absorption is the therapeutic aim required. Carbopol 940 when used as a tablet binder in a concentration of 2.5%, showed a marked enhancement of the release rate of the drug. On the contrary, it exerted a remarkable retardation in the rate of drug release from the tablets when incorporated in the relatively large proportions of 20, 35 and 50%. This retardation was more pronounced in alkaline than in acid media. Accordingly, Carbopol 940 would be favourably suggested in the physiocohemical design of prolonged-release tablet formulations.     

Enhancement of ibuprofen dissolution via wet granulation with beta-cyclodextrin

The purpose was to investigate the effect of wet granulation with beta-cyclodextrin (betaCD) on the enhancement of ibuprofen (IBU) dissolution. The effect of the granulation variables on the physical properties as well as the dissolution of tablets prepared from these granules was also examined. Granulation was performed using three granulating solvents: water, ethanol (95 vol%), and isopropanol. Granules were either oven-dried for 2 h or air-dried for 3 days. The granules or respective physical mixtures were compressed into tablets. Powder X-ray diffraction showed that oven-dried granulation resulted in less amorphous entities thatfacilitated IBU-betaCD complexation in solution and enhanced the dissolution of the corresponding tablets compared to the physical mixture with or without oven drying. In contrast, air-dried granulation did not cause any differences in the X-ray diffraction pattern (crystallinity) or the dissolution compared to the physical mixture without drying. Isopropanol and water, as granulating solvents, enhanced the dissolution of the oven-dried batches more than ethanol. The Differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA) data showed that tablets prepared from oven-dried granules, but not air-dried granules, had lower AH values and percent loss in weight, respectively, than those prepared from the physical mixture as a result of the expulsion of the water molecules from the betaCD cavity and enhancement of the complexation in solution. These results showed that oven-dried granulation of IBU and betaCD provided faster IBU dissolution than the physical mixture; air-dried granulation did not substantially affect the dissolution of IBU.     

Formation of simvastatin nanoparticles from microemulsion

The present study evaluates a new method to prepare nanoparticles of a poorly water-soluble drug, simvastatin, by evaporation of all solvents from spontaneously formed oil-in-water microemulsions. By this method, microemulsions containing a volatile solvent as an oil phase are converted into nanoparticles in the form of dry non-oily flakes by freeze-drying. The presence of simvastatin in nanoparticles was determined by dispersing the flakes in water and subsequent filtering through a 0.1-μm filter, followed by measuring the simvastatin concentration in the filtrate. It was found that after freeze-drying more than 95% of the drug was present in amorphous particles, smaller than 100 nm. It was found that tablets containing the flakes of simvastatin nanoparticles showed tremendous enhancement in dissolution profile compared with conventional tablets. X-ray diffraction revealed that in the resulting flakes simvastatin nanoparticles were initially amorphous, but a slow crystallization process took place when the product was stored at room temperature.From the Clinical EditorThis paper describes a new method to prepare nanoparticles of a poorly water-soluble drug, simvastatin, by evaporation of all solvents from spontaneously formed oil-in-water microemulsions. Tablets containing the flakes of simvastatin nanoparticles showed tremendous enhancement in dissolution profile compared with conventional tablets.     

Bioavailibility of paracetamol after oral administration to healthy volunteers

The absorption rate and the bioavailability of two commercially available paracetamol tablets were investigated in a panel of seven volunteers; one of these tablets contained a combination of 50 mg caffeine and paracetamol. Considering the urinary excretion data, it is concluded that the tablets release their contents completely; the absolute bioavailability, however, calculated from plasma concentrations, is lower than 100%, indicating a first-pass effect. A marked interindividual variation in first-pass effect was noticed. No general influence of caffeine on the extent of absorption of paracetamol could be established; there is, however, a slightly positive influence of caffeine on the absorption rate of paracetamol in six out of seven volunteers. It was concluded that this positive influence on absorption rate is not responsible for the established enhancement of paracetamol analgesia by caffeine.     

Effect of processing and formulation variables on the stability of a salt of a weakly basic drug candidate

The effect of some processing and formulation variables on the stability of tablets containing a crystalline salt of a triazine derivative was studied. The salt has a relatively low melting point and a low microenvironmental pH due to the weakly basic nature of the parent compound (pKa = 4.0). This compound decomposes through acid-catalyzed hydrolysis. A full factorial design was used to study the effect of three variables on tablet stability: aqueous wet granulation, ball milling of the salt and filler prior to manufacturing, and the inclusion of sodium carbonate in the formulation as a pH modifier. In addition to the factorial design experiments, a batch of tablets was prepared by wet granulation, using sodium bicarbonate as the pH modifier. Stability of the drug in tablets was evaluated at 40 degrees C/75% relative humidity (RH) and at 40 degrees C/ambient humidity. Stability of tablets was adversely affected by wet granulation. However, stability was greatly improved by wet granulation in the presence of sodium carbonate. While sodium carbonate enhanced drug stability in the tablets, regardless of the manufacturing process, wet granulated tablets were more stable than tablets containing sodium carbonate and prepared without wet granulation. Similarly prepared tablets by using sodium bicarbonate were remarkably less stable compared with those containing sodium carbonate. The use of sodium bicarbonate as a pH modifier resulted in only marginal enhancement of tablet stability, suggesting that a higher microenvironmental pH than that provided by sodium bicarbonate is needed to maximize stability. Despite the low lattice energy of the salt and the potential for disruption of salt crystallinity by mechanical stress, milling did not appear to have an adverse effect on tablet stability under the current experimental conditions. This study shows that selection of the proper manufacturing process, in conjunction with the appropriate pH modifier, could be critical to dosage form stability.     

Enhanced bioavailability of digoxin by gamma-cyclodextrin complexation: evaluation for sublingual and oral administrations in humans

The inclusion complex of digoxin with gamma-cyclodextrin was prepared in a molar ratio of 1:4, and evaluated for sublingual and oral administrations in humans. In the dissolution tests of digoxin tablets, the increase in dissolution rate and decrease in acid hydrolysis were attained by gamma-cyclodextrin complexation. The serum levels of digoxin after sublingual and oral administrations to human healthy volunteers in the form of complex tablets were higher than the digoxin alone, particularly in the case of the sublingual form of gamma-cyclodextrin complex. The present data suggested that the sublingual administration of the rapid dissolving form of gamma-cyclodextrin complex may be useful for improving the bioavailability of digoxin due to the prevention of acid hydrolysis in stomach and the enhancement of drug absorption rate.     

Particle agglomeration of chitosan–magnesium aluminum silicate nanocomposites for direct compression tablets

Exfoliated nanocomposites of chitosan-magnesium aluminum silicate (CS-MAS) particles are characterized by good compressibility but poor flowability. Thus, the aims of this study were to investigate agglomerates of CS-MAS nanocomposites prepared using the agglomerating agents water, ethanol, or polyvinylpyrrolidone (PVP) for flowability enhancement and to evaluate the agglomerates obtained as direct compression fillers for tablets. The results showed that the addition of agglomerating agents did not affect crystallinity, but slightly influenced thermal behavior of the CS-MAS nanocomposites. The agglomerates prepared using water were larger than those prepared using 95% ethanol because high swelling of the layer of chitosonium acetate occurred, allowing formation of solid bridges and capillary force between particles, leading to higher flowability and particle strength. Incorporation of PVP resulted in larger agglomerates with good flowability and high strength due to the binder hardening mechanism. The tablets prepared from agglomerates using water showed lower hardness, shorter disintegration times and faster drug release than those using 95% ethanol. In contrast, greater hardness and more prolonged drug release were obtained from the tablets prepared from agglomerates using PVP. Additionally, the agglomerates of CS-MAS nanocomposites showed good carrying capacity and provided desirable characteristics of direct compression tablets.     

Enhanced Permeation of an Antiemetic Drug from Buccoadhesive Tablets by Using Bile Salts as Permeation Enhancers: Formulation Characterization,In Vitro,and Ex Vivo Studies

Buccal bioadhesive bilayer tablets of prochlorperazine maleate were designed and formulated by using buccoadhesive polymers such as hydroxypropylmethyl cellulose, Carbopol 934P, and sodium alginate. Physicochemical characteristics like the uniformity of weight, hardness, thickness, surface pH, drug content, swelling index, microenvironment pH, in vitro drug release, and in vivo buccoadhesion time of the prepared tablets were found to be dependent on the type and composition of the buccoadhesive materials used. The effect of bile salts on the permeation was studied through porcine buccal mucosa and it was found that out of three bile salts incorporated (sodium glycholate, sodium taurocholate, and sodium deoxycholate), sodium glycholate enhanced the permeation rate of prochlorperazine maleate by an enhancement factor of 1.37.