In vitro and in vivo defoaming action of three antacid preparations

The defoaming activity of three tablet antacids (hydrotalcite, hydrotalcite/dimethicone and aluminium hydroxide/dimethicone) powdered to 60 mesh was measured in vitro using a new static/dynamic technique. Their antacid actions and that of aluminium hydroxide gel B.P.C. were also measured using a modified Fuch's test. Combination of dimethicone with hydrotalcite conferred good defoaming activity with little effect on pH profile whilst combination of aluminium hydroxide with dimethicone markedly altered both. Additionally, the defoaming actions of the three commercial antacids were assessed in vivo. Radiographs were taken after administration of antacid, a foaming mixture and a normal barium meal. The radiographs were then ranked blind by 5 radiologists. The rankings assigned the significantly greatest (Mann-Whitney U-test) defoaming effect to the hydrotalcite/dimethicone combination, there being no difference between the other two preparations. The in vitro results were thus confirmed.     

In vitro and in vivo bioequivalence of commercial prednisone tablets

The purpose of the study was to examine the bioequivalence of five commercially available oral prednisone products. The in vivo study utilized 18 healthy males, each of whom was administered 20 mg of prednisone as a reference solution or as a tablet in a 6-week, six-way crossover design. Blood was collected and serum was assayed, using an HPLC procedure specific for prednisone and prednisolone. Mean pharmacokinetic parameters (t 1/2, ke, Cmax, tmax, and AUC) were determined. ANOVA was performed on the prednisone and prednisolone data (F-test, p less than 0.05) as well as Duncan's multiple range analysis. Dissolution tests were also performed on each of the five products in order to test the relationship between dissolution and bioequivalence among prednisone products. The in vitro study consisted of a standard USP dissolution test which included tablets from the same lots as the tablets used in the in vivo study. The data showed no statistical difference in any of the pharmacokinetic parameters among tableted products, subjects, or dosing periods in the study. There was also no statistical difference in the dissolution study among the five commercial tablet forms.     

In vitro evaluation of three commercial sustained-release papaverine hydrochloride products.

Three commercial sustained-release papaverine hydrochloride products in the form of microencapsulated pellets were evaluated. Three different dissolution apparatuses were used: a continuous flow apparatus, the USP rotating basket apparatus, and a modified reciprocating basket apparatus. The frequency rate of the reciprocating basket apparatus could be varied from 0 to 31 strokes/min. Salicylic acid compacts were used as a standard to characterize each apparatus. A linear log--log correlation between dissolution rate and apparatus speed or flow rate was obtained. Release of papaverine hydrochloride from the commercial preparations was affected significantly by the pH of the dissolution media but not by the agitation intensity.     

In vitro and in vivo characteristics of some commercial phenobarbital tablets

Using an incompletely randomized crossover study design, the oral bioavailability characteristics of 7 different brands of phenobarbital tablets, USP, 100 mg was investigated in 5 adult, male volunteers. From plasma drug concentration-time data, best estimates for the bioavailability parameters of peak plasma phenobarbital concentration (Cmax) and time to peak concentration (tmax) were obtained by curve fitting and area under the plasma drug concentration-time curve (AUC) computed with the trapezoid rule. No significant difference in Cmax or normalized AUC was seen for the 7 products investigated. Additionally, a difference in tmax was observed between 2 preparations (A and E) only (p less than or equal to 0.05). All drug products met USP requirements for weight variation and tablet disintegration and all but one product (D) exhibited reasonably good and similar dissolution characteristics in simulated gastric fluid. No correlation between various in vitro dissolution parameters and in vivo bioavailability of phenobarbital could be found for the 7 phenobarbital products studied.     

In vitro evaluation of pectin-HPMC compression coated 5-aminosalicylic acid tablets for colonic delivery.

In this study, we report pectin-HPMC compression coated core tablets of 5-aminosalicylic acid (5-ASA) for colonic delivery. Each 100 mg core tablet contained 5-ASA and was compression coated at 20 kN or 30 kN using 100% pectin, 80% pectin-20% HPMC, or 60% pectin-40% HPMC, at two different coat weights as 400 or 500 mg. Drug dissolution/system erosion/degradation studies were carried out in pH 1.2 and 6.8 buffers using a pectinolytic enzyme. The system was designed based on the gastrointestinal transit time concept, under the assumption of colon arrival times of 6 h. It was found that pectin alone was not sufficient to protect the core tablets and HPMC addition was required to control the solubility of pectin. The optimum HPMC concentration was 20% and such system would protect the cores up to 6 h that corresponded to 25-35% erosion and after that under the influence of pectinase the system would degrade faster and delivering 5-ASA to the colon. The pectin-HPMC envelope was found to be a promising drug delivery system for those drugs to be delivered to the colon.     

秋水仙碱双层片体外释放研究

目的建立秋水仙碱双层片体外释放方法,并考察工艺、体外释放条件与缓速释比例对秋水仙碱双层片释药的影响。方法采用相似因子（f2）法评价释药曲线的相似性,并分别用零级、一级、Higuchi、Peppas方程拟合优化处方。结果工艺对秋水仙碱双层片影响较小,浆速对秋水仙碱双层片影响较大。依据最优处方制备的控释片在1～12h呈良好的缓释释放特征,12h累积释药率90％以上。结论建立了较为准确、可靠的秋水仙碱双层片体外释放度测定方法,体外释放度结果符合要求。     

格列齐特生物溶蚀性骨架片的制备及体外释放度研究

目的建立格列齐特缓释片的释放度测定方法。方法采用转蓝法,以pH 7.4磷酸盐缓冲液为溶出介质,转速为100 r.m in-1,照分光光度法检测,测定波长226 nm。结果格列齐特2.04~20.40 mg.L-1范围内吸收度与浓度呈良好的线性关系,r=0.999 9,平均回收率为100.9%,RSD=1.07%(n=12),与国外上市的同规格产品D iam icronMR一致。结论方法操作简便,准确可靠,可用于格列齐特缓释片的质量控制。     

雷诺嗪缓释片体外释放度的测定

目的建立雷诺嗪缓释片的体外释放度测定方法。方法以0.9%的盐酸水溶液为溶出介质,溶出方法为转篮法(100 r.min-1)。结果采用紫外分光光度法在272 nm测定雷诺嗪的浓度,其检测线性范围为10～200 mg.L-1(r=0.999 9),平均回收率为98.04%(RSD=1.26%);3批样品在2、6、12 h的释放量分别为标示量的30%、60%、70%以上。结论该方法准确、可靠,可用于该制剂的释放度测定。     

Formulation of intelligent tablets with an antacid effect

Matrix systems with a local antacid effect were produced in this study. Aluminium hydroxide and magnesium trisilicate in constant concentrations were used as active agents. Eudragit^® E PO was applied as a matrix former and sodium bicarbonate as a disintegrant (third antacid component), in different ratios. Their effects on the properties of the tablets were studied. Such formulated systems must be insoluble if the pH of the stomach is less acidic, but a rapid disintegration must occur if necessary. It can be concluded that Eudragit^® E PO in appropriate composition can ensure tablets with pH-dependent disintegration. Its binding effect allows tablet making from the elastic active component. The liberation of antacid materials from this system is controlled. If the pH reached 2.5, the erosion of the tablet was reduced. In contrast with expectations, the application of poorly compressible and effervescent sodium bicarbonate increased the time for disintegration of the tablets, because of its extended alkalizing effect around the tablet. This system with this acrylic component is appropriate to produce a controlled-release local antacid preparation.     

In Vitro andIn Vivo availability of some commercial prednisolone tablets

The in vitrodissolution rates of prednisolone from five commercially available 5- mg prednisolone tablets were determined in distilled water. The dissolution studies were repeated on the fastest- and slowest-dissolving brands using 0.01% polysorbate 80 in 0.1 NHCl as the dissolution medium. A two-way crossover bioavailability study was performed in 12 human male adult volunteers comparing the fastest- and slowest-dissolving brands. The plasma samples were assayed for prednisolone by a radioimmunoassay method. Statistical analysis of the data for the two brands showed no significant differences between average plasma levels of prednisolone at any sampling time. The results suggest that on the average the in vivorates of dissolution of the two brands were essentially the same, and in vitrodissolution in 0.01% polysorbate 80–0.1 NHCl medium was better correlated with these in vivoresults than dissolution in water.Supported by Contract CPF69-22, Food and Drug Administration, Washington, D.C., and in part by Public Health Service Grant 5-P11-GM15559.     

In vitro dissolution and in vivo bioavailability of commercial levothyroxine sodium tablets in the hypothyroid dog model

The objective of this study was to determine whether a correlation exists between the rate of in vitro dissolution and bioavailability of levothyroxine sodium (T4) tablets. Dissolution versus time profiles for Synthroid, the Flint brand of levothyroxine sodium, and two competitors' tablets (brands A and B) were generated using an official dissolution apparatus (USP), and 0.05 M phosphate buffer (pH 7.4) as the medium. These tablets were also utilized in single-dose crossover bioavailability studies in the hypothyroid dog model (n = 6). The average areas under the serum T4 concentration versus time curve from 0 to 8 h (AUC) for Synthroid, brand A, and brand B were 8.22, 6.32, and 8.70 ng-h/mL per dose (micrograms per kg body weight), respectively. Respective peak serum concentrations (Cmax) for each tablet formulation were 1.26, 1.07, and 1.36 ng/mL per dose. The corresponding dissolution rates, expressed as t50%, were 20.5, 3.06, and 14.1 min, respectively. Data analysis indicated no correlation between dissolution kinetic parameters and the bioavailability parameters AUC and Cmax. However, a linear relationship was observed between dissolution kinetics and both the time to reach maximal serum concentration (tmax) and the observed absorption rate constant (ka).     

Influence of in vitro test conditions on release of aspirin from commercial tablets.

The influence of in vitro test conditions on the release of aspirin from commercial tablets was assessed with a USP rotating-basket dissolution apparatus. Three types of aspirin tablets were evaluated: plain, buffered, and microencapsulated. The variables investigated were stirring speed, pH, and volume and temperature of the dissolution medium. Plain tablets gave the best dissolution profiles under all experimental conditions, except at pH 3. Microencapsulated tablets showed sustained release. For all three types of tablets, faster dissolution was observed at pH 4.5 compared with that in artificial gastric juices. Increasing the stirring rate increased the dissolution rate, an effect most pronounced for plain tablets. Very similar dissolution curves were obtained when the dissolution test was conducted in 500 and 900 mL of dissolution media regardless of the pH of the media. No significant difference in dissolution profiles was observed when the effect of temperature was investigated. The dissolution data were evaluated on the basis of theoretical dissolution equations and by linear transformation of dissolution curves. Highly significant linear correlation coefficients revealed that the cube root equation could be used to describe drug release in artificial gastric juices, regardless of tablet type. When pH 4.5 buffer solution was used as the dissolution medium, different kinetic models were applicable.     

In vitro genotoxic evaluation of three alpha-asarone analogues.

alpha-Asarone has shown a significant capacity to reduce the level of lipids, including cholesterol. However, several toxic and genotoxic studies have determined that its use may pose a risk to human health. Therefore, a series of compounds structurally analogous to alpha-asarone were prepared in order to maintain the same pharmacological properties but with low toxicity. In this study we evaluated the potential of three alpha-asarone analogues to induce mutagenicity using the Ames test (strains TA98 and TA100 in the presence of metabolic activation), as well as the induction of sister chromatid exchanges (SCE) in cultured human lymphocytes. The tested compounds were: 1-(2,4,5-trimethoxyphenyl)propan-1-one (D1), 1-(2-chloro-4,5-dimethoxyphenyl)propan-1-one (D2), and 1-(4,5-dimethoxy-2-nitrophenyl)propan-1-ol (D3). The results in the first assay showed no mutagenic effect for the three tested analogues; in the TA100 strain, certain cytotoxicity did appear in the case of D2 and D3 only at high concentrations. In regard to the SCE assay, compounds D1 and D2 presented no statistical differences in comparison with the control culture values; however, the high dose of D3 (300 microg/ml) produced a significant increment in SCE (68% above the control value). With respect to the mitotic index and the cellular proliferation kinetics, we observed a reduction when compounds D2 and D3 were used at the higher concentrations. Our results encourage further preclinical studies of these compounds in both in vitro and in vivo models (particularly for analogues D1 and D2), to determine their toxicological profile and establish the possibility of using them in humans.