尼莫地平控释片释放度试验研究

本文研究了尼莫地平控释片的释放度试验方法——转篮法，释放介质为含有２２％异丙醇的０．１ｍｏｌ·Ｌ－１盐酸液；磷酸盐缓冲液（ｐＨ５．８）和ｐＨ７．２的溶液。含量测定方法：紫外分光光度法，在三种介质中尼莫地平分别在１～３０μｇ·ｍｌ－１，１０～５０μｇ·ｍｌ－１和１０～５０μｇ·ｍｌ－１的范围内，浓度与吸收度有较好的线性关系。回归方程分别为Ａ＝０．６１５Ｃ＋０．０２３（ｒ＝０．９９９９）；Ａ＝０．０６１４Ｃ＋０．０１２（ｒ＝０．９９９５）；Ａ＝０．０６１２Ｃ＋０．００８８（ｒ＝０．９９９９）。平均回收率分别为９９．６３％，９９．９８％及１００．７７％，ＲＳＤ（％）分别为１．３４％，１．５９％及１．４１％。本方法的体外释放百分率与体内吸收分数有较好的相关性（ｒ＝０．９９１）。     

应用光纤药物溶出仪对硝苯地平缓释片释放度的考察

目的:对硝苯地平缓释片进行全程的实时、原位在线释放度测定,并与该品种已有国标[1]释放度测定结果进行比较.方法:运用FODT-601光纤药物溶出仪,选择237/550 nm双波长法,消除赋形剂干扰,按该品种已有国标释放度检查项溶出条件,测试该药物溶出曲线,并与按国标方法测得的溶出曲线进行比较.结果:在3.37μg·mL-1～17.83μg·mL-1范围内,浓度(C)与吸光度(A)呈良好的线性关系,浓度对应的溶出量(Q)% 与吸光度(A)也呈良好的线性关系,相关系数均在0.9990以上;3个浓度各3份样在6个通道的平均回收率分别为98.52%、99.22%、98.78%;对应的RSD(n=18)分别为1.1%、0.7%、0.7%,溶出曲线与国标方法测定的溶出曲线无显著性差异(P>0.05).结论:硝苯地平缓释片光纤药物溶出仪测定结果与按常规国标方法测定结果基本一致,而且该法具有操作简便,测定快速,获取信息量更大的优点.     

维体舒肠溶衣片释放度检查研究

目的：研究采用适当方法增加维体舒肠溶衣片释放度检查。方法：采用紫外分光光度法测定维体舒肠溶衣片酸及磷酸盐缓冲液中乙酰水杨酸释放量。结果：乙酰水杨酸释放量测定在3．55μg／ml～35．5μg／ml有良好的线性关系,回收率可达99．7％。结论：增加了该制剂释放度检查,释放量测定方法简便、灵敏、具有实用性。     

反相高效液相色谱法测定达美康缓释片中格列齐特的含量

目的：建立以反相高效液相色谱法（HPLC）测定格列齐特缓释片含量的方法。方法：色谱柱为HypersilODSC18色谱柱,流动相为甲醇-水（60∶40）,以格列吡嗪为内标物,检测波长为228nm,流速为1.0ml/min。结果：格列齐特在4～64μg/ml浓度范围内线性关系良好（r=0.9998）,平均加样回收率为99.83%（RSD=1.04%）。结论：本方法简便、准确、灵敏度高、重现性好,可用于测定格列齐特制剂的含量测定。     

影响石杉碱甲骨架片体外释放因素的研究

目的自制石杉碱甲骨架缓释片（HA-MT），考察石杉碱甲骨架片中释放的体外释放特性。方法考察通过释放度实验研究不同制片工艺、测定方法、释放介质的pH值、搅拌转速对骨架片释药的影响，并考察其释药机制。结果制片方法、测定方法对释药行为影响不明显，但转速和溶出介质有明显影响。药物释放曲线符合HIGUCHI方程。结论制备的HA-MT工艺简易，释药达到缓控释要求，释药机制为扩散和溶蚀机制协同作用。     

Teratological evaluation of FD&C Red No. 2-a collaborative government -industry study. IV. NCTR's study.

Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, an ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA),Industrial Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.     

Automated in vitro dissolution rate analysis of potassium in plastic matrix slow release tablets.

A fully automated system for dissolution rate analysis of potassium in slow release tablets is described. Aliquots are removed after 1, 2, and 4 hr from six samples, and potassium is analyzed in a flame photometer at 768 nm. A complete study of six samples takes 5.5 hr. The system may be run overnight. During the time intervals between the removal of aliquots, the system can be used for the determination of the total assay of tablets.     

两种国产盐酸西替利嗪片溶出度比较

目的考察盐酸西替利嗪片的体外溶出度,为评价其质量提供参考。方法 采用转篮法测定溶出度,用威布尔(Wcibull)分布模型拟合溶出曲线,并对溶出参数m、T50、Td等采用t检验进行统计分析。结果 两厂家盐酸西替利嗪片的溶出参数无显著性差异(P>0.05)。结论 两国产厂家制剂的溶出度均符合规定。     

Correlation of absorption of sulfamethazine boluses with dissolution using a new dissolution apparatus for veterinary tablets.

A rotating-basket apparatus for dissolution testing of veterinary bolus tablets was designed and constructed. Sulfamethazine boluses containing different disintegrating agents were evaluated in vitro and by blood level data following administration to cattle. The dissolution t50 and various pharmacokinetic parameters showed directly compressible starch and carboxymethylstarch to be the most effective disintegrants in the concentrations employed while magnesium aluminum silicate and microcrystalline cellulose were about equal but less effective than the previous disintegrants. A bolus formulation containing no disintegrant gave even less satisfactory results. A correlation was established between the dissolution t50 and the time to peak plasma level and also between the t50 and the area under the plasma-time curve for the first 36 hr.     

洛汀烟酸缓释片中洛伐他汀溶出度的测定

目的建立了洛汀烟酸缓释片中洛伐他汀溶出度测定方法。方法采用转蓝法,以2%十二烷基硫酸钠溶液1 000 m l(内含1.38 g磷酸二氢钠,并用1 mol.L-1氢氧化钠溶液调pH至7.0)为溶出介质,转速为75 r.m in-1,采用HPLC法检测。结果洛伐他汀在2.5~25 mg.L-1范围内峰面积与浓度呈良好的线性关系,r=0.9998,平均回收率为97.39%,RSD=1.68%(n=9),与国外同品种AdvicorTM中洛伐他汀溶出度一致。结论方法准确可靠,可用于洛汀烟酸缓释片的质量控制。     

Collaborative study of the USP dissolution test for prednisone tablets with Apparatus 2

Five lots of prednisone tablets that disintegrate within 5 min were collaboratively studied by 11 laboratories using USP Apparatus 2 under carefully controlled conditions. One lot gave complete dissolution. The reproducibility and repeatability of Apparatus 2 for the four lots still dissolving at the end of the test were 2.6 and 1.6% of label claim, respectively, for the 11 laboratories.     

The effect of formulation composition and dissolution parameters on the gel strength of controlled release hydrogel tablets.

The impact of hydrogel polymers and dissolution media on tablet gel strength, Gamma, of controlled release (CR) hydrogel tablets was investigated. CR tablets containing either hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), or carbomer were formulated with theophylline and Fast Flo lactose, to produce tablets with a polymer content of 8, 15, and 30% w/w. Gamma was measured using a previously reported method. The drug dissolution profiles were similar, irrespective of polymer type or dissolution media (DI water, 0.1 N HCl, and pH 6.8 phosphate buffer), at the same % w/w level of polymer. Gamma, however, showed large and significant differences (p < or = 0.05) between tablets containing different polymers and between different dissolution media. Gamma values were HPMC KI00MP > HPC HXF > carbomer 971P (same % w/w) with absolute Gamma values at 30% w/w in DI water of 6600, 4600, and 1600 ergs/cm3, respectively. Gamma for HPMC based tablets was independent of changes in dissolution media, while the Gamma values for HPC tablets were 18% lower in acid and buffer than in DI water. Of the polymers tested, carbomer based tablets had the lowest Gamma values in all dissolution media and an unexpected 58% lower Gamma in buffer compared with DI water or acid. Gamma provides a quantitative measure of the effect of formulation and dissolution parameter changes on tablet gel layer strength, under in vitro stress conditions that may parallel in vivo tablet performance, but which cannot be deduced from a comparison of dissolution profiles or polymer viscosity.     

In vitro/in vivo correlations of dissolution data of carbamazepine immediate release tablets with pharmacokinetic data obtained in healthy volunteers.

The aim of the study was to select a dissolution test method for carbamazepine (CBZ) immediate release tablets, giving the best in vitro/in vivo correlations (IVIVC) and to determine the potential of this method as an estimate for bioequivalence testing. Four 200 mg CBZ products which are sold on the Dutch market, covering the innovator and three generic products, were selected. They had been tested in a randomised, fourway cross-over bioavailability study in healthy volunteers. Their dissolution rate behaviour in vitro was investigated in two dissolution media: (1) 1% sodium lauryl sulphate in water (SLS), in accordance with the United States Pharmacopeia (USP); (2) 0.1 mol/l Hydrochloric acid in water (HC). In the bioavailability study these products had shown no large differences in the extent of absorption (AUC(0-infinity);) but large differences in absorption rate. The products now also showed large differences in dissolution rate in vitro in both dissolution media, the rank order being the same as for the absorption rate. It was concluded that the absorption rate in vivo depends on the dissolution rate in vivo. 'Level C' IVIVC according to the USP were optimised by plotting percentages dissolved on selected time points (D values) or their reciprocals (1/D values), against several pharmacokinetic parameters primarily related to the absorption phase and against AUC(0-infinity). In this way for each IVIVC the optimum D or 1/D value, was calculated. For both media no meaningful IVIVC were obtained with AUC(0-infinity), but favourable IVIVC were obtained with the parameters primarily related to the absorption phase. In the bioavailability study indicated above it was found that, among the pharmacokinetic characteristics primarily related to the absorption phase, C(max) is the most promising in expressing rate of absorption in bioequivalence testing in single dose studies with CBZ immediate release tablets. Consequently, C(max) was selected for expressing rate of absorption. The most favourable IVIVC were obtained with D(20) in SLS versus C(max). From this IVIVC and the requirements for bioequivalence (AUC(0-infinity): 0.8-1.25 and C(max) : 0.75-1.35; 90% confidence interval), a specification for dissolution testing in SLS was calculated as follows: 'after 20 minutes, 34-99% dissolved'. Owing to the fact that the rate of absorption in vivo depends on i.a. the dissolution rate in vivo, it can be concluded that with this specification bioequivalence with respect to both rate of absorption and extent of absorption is ensured. As this specification is comparable with the USP specification: 'not less than 75% dissolved after 1 h', it is concluded that the USP specification is suitable to ensure bioequivalence of CBZ immediate release tablets.     

Development and in-vitro evaluation of modified release tablets including ethylcellulose microspheres loaded with diltiazem hydrochloride

In this study, development of modified release tablet formulations containing diltiazem hydrochloride-loaded microspheres to be taken once rather than two or three times a day was attempted. For this purpose, ethylcellulose microspheres were prepared by emulsion-solvent evaporation technique. The influence of emulsifier type and drug/polymer ratio on production yield, encapsulation efficiency, particle size, surface morphology and in-vitro release characteristics of the microspheres was evaluated. Suitable microspheres were selected and tabletted using different tabletting agents, Ludipress, Cellactose80, Flow-Lac100 and excipients Compritol888 ATO, KollidonSR. Tablets were evaluated from the perspective of physical and in-vitro drug release characteristics. It was seen that type and ratio of the excipients played an important role in the tabletting of the microspheres. As a result, two tablet formulations containing 180 mg diltiazem hydrochloride and using either Compritol888 ATO or KollidonSR were designed successfully and maintained drug release for 24 h with zero order and Higuchi kinetics, respectively.