双氯芬酸钠甲基纤维素骨架片体外释药的影响因素研究

目的探讨影响甲基纤维素(MC)亲水凝胶骨架片体外释药的因素。方法以双氯芬酸钠(DS)为模型药物,选取MC为骨架材料,观察MC用量、黏合剂选择、压片压力大小对MC亲水凝胶骨架片体外释药的影响。结果 MC用量、压片压力对骨架片的体外释药有较大影响,而黏合剂性质对骨架片的体外释药影响不显著。结论 MC可作为DS骨架片的骨架材料;MC用量、压片压力均影响骨架片的体外释放。     

双氯芬酸钠肠溶片的制备及其处方优化

目的：制备更优质的双氯芬酸钠肠溶片。方法采用粉末直接压片及高效包衣机包衣法制备了双氯芬酸钠肠溶片,从片芯及包衣层两方面对处方进行筛选及优化。结果所制得的双氯芬酸钠肠溶片在人工胃液中耐酸力良好,在人工肠液中的溶出迅速且完全。结论研制了双氯芬酸钠肠溶片,解决了双氯芬酸钠对胃部刺激较大的问题,重现性好,工艺可行。     

Formulation and biopharmaceutical evaluation of osmotic matrix tablets of diclofenac sodium

The objective of our study was to prepare and evaluate osmotic matrix (OM) tablets of diclofenac sodium (DS). In vitro studies were done on USPXXIV dissolution apparatus II in different release medium. Surface characteristics of coating films and osmotic contribution of OM tablets also were studied. In vivo evaluation was carried out in 6 healthy human volunteers using HPLC method to assay plasma samples, and the results were compared with the performance of fabricated matrix and two commercial tablets of DS. Through in vitro drug release kinetics, using regression coefficient analysis and Peppas equation, different pharmacokinetic parameters and relative bioavailability were determined. OM tablets were found to provide more prolonged and controlled therapeutic plasma DS levels and also showed improved bioavailability in comparison to fabricated matrix and commercial tablets studied.     

Preparation and in vitro evaluation of sustained release tablet formulations of diclofenac sodium

The effects of formulation variables on the release profile of diclofenac sodium (DS) from hydroxypropylmethyl cellulose (HPMC) and chitosan matrix tablets were studied. DS tablets were prepared by wet granulation and direct compression methods and different ratios of HPMC and chitosan were used. Physical properties of the prepared tablets and targeted commercial sustained release (SR) tablet and the drug release were studied in tablets that were placed in 0.1 M HCl for 1 h and phosphate buffer solution was added to reach pH value of 7.5. In vitro studies showed that 20% HPMC contained SR formulation with direct (dry) compression method is the optimum formulation due to its better targeting profile in terms of release. This formulation also exhibited the best-fitted formulation into the zero order kinetics. The precision and accuracy of the analytical method were also checked. The repeatability and reproducibility of the method were also determined.     

HPLC法测定双氯芬酸钠凝胶中双氯芬酸钠的含量

目的采用HPLC法测定双氯芬酸钠凝胶中双氯芬酸钠的含量。方法以十八烷基键合硅胶为填充剂;用甲醇-0.005 mol/L磷酸二氢钾溶液(p H=3.8)(70∶30)为流动相;检测波长:280 nm;流速:1.0 m L/min;外标法测峰面积定量。结果双氯芬酸钠在15.90~55.41μg/m L(r=0.999 0)范围内线性关系良好,平均回收率为100.48%,RSD为1.28%。结论本方法简便、快速、准确,可用于双氯芬酸钠凝胶中双氯芬酸钠的含量测定。     

Calcium phosphates in pharmaceutical tableting

Ten commercially available calcium phosphates used for direct tableting were evaluated. The particle size distributions, powder properties, Sorption isotherms and pH values of aqueous slurries were compared. All samples showed good or at least sufficient flowability. Scanning electron micrographs illustrated the different kinds of manufacturing and gave hints on their expectable behaviour under compaction pressure. The sorption isotherms of identical chemical substances, which had been manufactured by different methods, differed strongly. This can be related to their specific surface areas. Most of the hydroxylapatites have large surface areas and can absorb up to more than 15% water at 93% relative humidity. Dibasic calcium phosphate dihydrate was non-hygroscopic and absorbed less than 1% water. With the exception of monobasic calcium phosphate monohydrate all calcium phosphates behaved quite neutral in water. Monobasic calcium phosphate monohydrate can be regarded as a solid acid. Although the calcium phosphates are usually stable substances, the role of crystal water in the case of dibasic calcium phosphate dihydrate and monobasic calcium phosphate monohydrate is problematic due to possible interactions with active ingredients.     

利巴韦林分散片的制备及稳定性评价

目的研究利巴韦林分散片的处方和制备工艺。方法对按笔者自我设计配方制备的4种利巴韦林分散片,采用高效液相色谱法测定溶出度及进行稳定性评价。结果以处方3工艺制成的片剂,质量可控,稳定性较好。结论处方3工艺成熟,质量稳定,是一种易于服用、奏效快的新制剂。     

双氯芬酸钠肠溶微丸型片剂的研制

本文制备了双氯芬酸钠肠溶微丸型片剂。以丙烯酸树脂EudragitNE30D和EudragitL30D-55不同比例的混合物作为衣膜材料，对不同粒径大小的双氯芬酸钠速释丸芯进行不同增重水平的包衣，并与不同压缩特性和用量比例的缓冲微丸混合，压片。所得的双氯芬酸钠肠溶微丸型片剂在人工胃液中2 h内累积释放百分数<10%，在人工肠液中1 h内累积释放百分数为(83±2.42)%。结果表明EudragitNE30D与EudragitL30D-55以一定比例混合制备得到适合压片的肠溶微丸，硬脂酸制备的缓冲微丸可用于微丸型片剂的制备。     

氟伐他汀钠分散片的制备

目的制备氟伐他汀钠分散片。方法以崩解时间为指标,采用正交设计试验,对氟伐他汀钠分散片处方进行筛选。结果乳糖、微晶纤维素(MCC)各40%为填充剂,MCC、羧甲基淀粉钠(CMS-Na)5%和低取代羟丙基纤维素(LS-HPC)10%为崩解剂,湿法制粒制备分散片。进行了溶出度实验。符合中国药典中有关分散片的要求。结论所制分散片处方合理,崩解快、溶出快而完全。     

双氯芬酸钠缓释片的制备和体外释放度研究

目的:研制双氯芬酸钠缓释片,并考察其释放度和稳定性.方法:释放介质选用经脱气处理的蒸馏水900 mL,用紫外分光光度法测定双氯芬酸钠缓释片0.5,2,4,8 h不同时间的累积释放量,测定波长276 nm,转速100 r·min-1.结果:该缓释片体外近零级释放,符合原设计要求,稳定性较好.结论:所研制的双氯芬酸钠缓释片工艺简单,稳定性好,能满足批量生产的要求.     

Pharmacokinetics of intravenous diclofenac sodium in children

Summary Diclofenac sodium 0.5 mg/kg i. v. was given preoperatively to small children (age 4–6 y). V_t and total plasma clearance were higher than in adults but the elimination half-life was similar.     

In vitro and in vivo evaluation of diclofenac sodium loaded album in microspheres

The use of polymeric carriers in formulations of therapeutic drug delivery systems has gained widespread application, due to their advantage of being biodegradable and biocompatible. Among the microparticulate systems, microspheres have a special importance since it is possible to target drugs and provide controlled release. Diclofenac sodium (DS), is a potent drug in the NSAID group having non-steroidal, anti-inflammatory properties, and is widely used in the treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. In this present study, it was aimed to prepare microsphere formulations of DS using a natural biodegradable polymer as a carrier for intraarticular administration to extend the duration period of the dosage form in the knee joint. Microsphere formulations of DS which were prepared were evaluated in vitro for particle size, yield value, encapsulation efficiency, surface morphology, and in vitro drug release. Two appropriate formulations were selected for in vivo trials. For the in vivo studies, Technetium-99m labelled polyclonal human immunogammaglobulin (99mTc-HIG) was used as the radiopharmaceutical to demonstrate arthritic lesions by gamma scintigraphy. After the induction of arthritis in knee joints of rabbits, the radio-labelled microspheres loaded with DS were injected directly into the articular cavity and at specific time points gamma scintigrams were obtained to find the residence time of the microspheres in knee joints in order to determine the most suitable formulation.     

双氯芬酸钠明胶微球的制备及体内外释药的研究

目的将双氯芬酸钠制备成明胶微球,考察其缓释效果。方法采用单凝聚法制备双氯芬酸钠明胶微球,并对微球的体内外释药进行考察。结果制备的微球粒径范围为48～100μm,平均粒径为70.70±11.29μm,载药量为35%。体内外释药实验结果表明双氯芬酸钠明胶微球有缓释作用。结论本法制备的双氯芬酸钠明胶微球能够起到明显缓释作用。     

盐酸洛美沙星胶囊和片剂的体外溶出度

目的　对盐酸洛美沙星胶囊和片剂进行溶出度测定 ,以考察其质量。方法　采用转篮法 ,以 0 1mol·L- 1 盐酸为溶出介质 ,检测波长 2 87nm ,研究洛美沙星胶囊和片剂的溶出度。结果　根据Weibull分布模型 ,计算出溶出参数T0 5、Td、T0 8和m。结论　各厂家的产品在 30min时 ,累积溶出量均大于 80 % ,符合规定。不同厂家的胶囊溶出度无显著性差异 (P >0 0 5 ) ,而不同厂家的片剂溶出度有极显著差异 (P <0 0 1)。建议对每批产品进行溶出度检查 ,控制其质量 ,保证临床疗效     

In vitro and in vivo evaluation of controlled-release and enteric-coated formulations of sodium salicylate

The bioavailability and pharmacokinetics of salicylic acid (SA) were studied after single and multiple doses of a new slow-release formulation, based on porous membrane diffusion of sodium salicylate (NaSA). A solution of NaSA and an enteric-coated tablet of NaSA were used for comparison. Dissolution rate studies were carried out at various pH values, and both solid formulations showed pH-dependent release rates. The entericcoated tablet released its content rapidly at intestinal pH but slowly and irregularly at gastric pH. The dissolution from the controlled-release formulation at intestinal pH was completed after 6 h and the drug was delivered at a constant rate. At gastric pH the release rate was lower but complete release was obtained within 24h. The novel formulation appeared to offer complete bioavailability of SA and an even and sustained release of SA, allowing twice-daily medication without increased fluctuations in SA concentrations.     

Effects of plasticizers and surfactants on the film forming properties of hydroxypropyl methylcellulose for the coating of diclofenac sodium tablets

Hydroxy propyl methyl cellulose (HPMC) 5cPs, an aqueous soluble polymer was employed for coating diclofenac sodium (DFS) tablets 25 mg for protecting the integrity of the drug yet rendering the drug to release at a faster rate on contact with the gastric environment. Proper optimization for the aqueous based film coating formulation was undertaken primarily employing plasticizers like polyethylene glycol (PEG) 400 and propylene glycol (PG). The defect free selected formulations were further subjected for studying the effects of surfactants like sodium lauryl sulphate (SLS) and Tween-80 along with the plasticizers. The quality of the aqueous film coats or the plasticizer efficiency in case of PEG-400 is in the order 1.5 > 0.5 > 1.0% and for PG 1 > 4 > 3% which can be stated on the basis of less incidence of major coat defects like chipping, cracking, orange peel, roughness, blistering, blooming, picking. The quality of aqueous film coat or the surfactant efficiency in case of SLS + PEG-400 is in the order 0.3 < 0.5 < 0.1% and SLS + PG is in the order 0.5 < 0.1 < 0.3%. In case of Tween-80 + PEG-400 the order is 0.3 < 0.5 < 0.1% and Tween-80 + PG is in the order 0.3 < 0.1 < 0.5%. Elegant film formation can be stated from fewer incidences of coat defects. The obtained coated tablets eventually satisfied all the normal physical parameters like thickness, weights, and weight gain, drug content, crushing strength, percent friability, disintegration time, dissolution profile and possible drug–polymer interactions. ANOVA was undertaken followed by Dunnet multiple comparison for the dissolution profile considering uncoated as the standard. The difference was considered significant at p ⩽ 0.01.     

乳化溶剂扩散法制备吲哒帕胺缓释微球

目的制备吲哒帕胺缓释微球。方法以乙基纤维素和水溶性高分子材料聚乙二醇6000为载体,采用乳化溶剂扩散法制备吲哒帕胺缓释微球,通过正交设计试验优选了处方和制备工艺,并对所制微球的形态、粒径分布、载药量和包封率等进行了考察。结果该法所制微球外观圆整、流动性好,粒度分布在80～200μm范围内的微球占总数的84.5%,载药量为36.8%,包封率为78.1%。结论该法可用于吲哒帕胺缓释微球的制备。     

Bioequivalence studies of a new valproic acid delayed-release capsule and divalproex sodium delayed-release tablet

ABSTRACT

Objective: The study examined relative bioavailability of a novel valproic acid (VPA) delayed-release (DR) soft gelatin capsule formulation to divalproex sodium DR tablet under fasting conditions and the effect of food on the bioavailability of the VPA DR soft gelatin capsule.

Method: This open-label, randomized three-way crossover study enrolled 36 healthy non-smoking adult volunteers. Treatments included a single 500 mg divalproex sodium DR tablet, fasting; a single 500 mg VPA DR soft gelatin capsule, fasting; and, a single 500 mg VPA DR soft gelatin capsule 500 mg, non-fasting. Analysis of variance was performed on the pharmacokinetic parameters. The ratio of geometric means and corresponding 90% confidence intervals (CI) were calculated on ln-transformed data for the area under the serum concentration-time curve (µg-hr/mL) from time zero to the time of the last quantifiable concentration (t) (AUC_0–t), AUC_0–∞ and maximum plasma concentration (C_max). Bioequivalence was shown when 90% CIs were within the 80–125% range.

Results: All subjects completed the study. The 90% CIs of VPA DR soft gelatin capsules compared to divalproex sodium DR tablets were within the 80–125% limits for AUC_0–t, AUC_0–∞, and C_max. The time of maximum or peak concentration (T_max) of VPA DR soft gelatin capsules was 2.3 hours versus 3.7 hours with divalproex sodium DR tablets. AUC_0–t and AUC_0–∞ of VPA soft gelatin capsules were not affected in the non-fasting condition, but T_max occurred at 6.1 hours compared to 2.3 hours fasting. Eight subjects experienced a total of 10 adverse events; none were serious.

Conclusion: The VPA DR soft gelatin capsule formulation was shown to be bioequivalent to divalproex sodium DR tablet and no serious adverse events occurred. Because this was not a multiple-dose study, however, direct comparisons in chronic dosing were not possible. Administration with food affected rate but not extent of absorption of the VPA DR soft gelatin capsules, but comparisons with the reference product were not conducted under non-fasting conditions.     

外用双氯芬酸钾凝胶治疗局部风湿性疼痛综合征

目的 比较研究双氯芬酸钾凝胶（ＤＰＧ）和双氯芬酸钠凝胶（ＤＳＧ）治疗局部风湿性疼痛综合征的疗效和安全性。方法 试验设计为多中心、随机对照、单盲、平行性的比较研究。试验组 ６０例,１％ＤＰＧ外用,每日３－４次,每次２－４ｇ,日总量不超过２０ｇ,疗程２周;对照组４５例,１％ＤＳＧ外用,使用方法同ＤＰＧ。结果 ２周时ＤＰＧ的总有效率为 ８８％,ＤＳＧ总有效率为８７％,ＤＰＧ组疗效明显高于 ＤＳＧ组（Ｐ＜０．０５）。两药均能显著改善病人的临床症状和体征（Ｐ＜０．０５～０．００１）,两组相比ＤＰＧ对关节肿胀数的改善优于ＤＳＧ组（Ｐ＜０．０５）,对其他各指标的改善两组间差异无显著性（Ｐ＞０．０５）． ＤＰＧ的耐受性良好,无１例病人发生不良反应;ＤＳＧ组的不良反应发生率为２％,两组间差异无显著性（Ｐ＞０．０５）．结论ＤＰＧ治疗局部风湿性疼痛综合征的疗效优于ＤＳＧ,且耐受性好,无明显不良反应。     

HPLC法测定盐酸马尼地平片的溶出度

目的采用HPLC法测定盐酸马尼地平片的溶出度。方法 Accurasil C18柱（4.6mm×250mm,5μm）;流动相为磷酸盐缓冲液-乙腈（45∶55）;检测波长为228nm。结果盐酸马尼地平在0.002-0.006mg.mL^-1浓度范围内,线性关系良好,r=0.9994。结论本方法准确,重现性好,可用于盐酸马尼地平片的溶出度测定。