Results Of Dissolution Tests Research Articles

The effect of the drug/polymer ratio on the properties of the verapamil HCl loaded microspheres

In this study, the microspheres containing verapamil hydrochloride (VRP) were prepared with Eudragit RS 100 by solvent evaporation method. In the solvent evaporation method one of the parameters which affect to the formation and properties of the microspheres is the variations of drug/polymer ratios. The aim of our study is to examine the effects of this parameter on the VRP loaded microspheres. To achieve this purpose, only drug/polymer ratio was altered while the other formulation parameters were kept constant and percentage yield value, incorporation efficiency, particle size and distribution of the microspheres were analyzed and micrographs of the microspheres were taken to determine the effects of the increase in the polymer amount of formulations. All the dispersed phase viscosities were evaluated by comparing them with the variations in particle size and distribution of the microspheres. In vitro dissolution tests were done by using dissolution media with three different pH in sequence as half-change method with flow through cell and the effect of the variation in polymer ratio on drug dissolution was evaluated according to dissolution test results. As a result of our study, it is thought that the variation in drug/polymer ratios might have an influence on the physical characteristics of the microspheres and the increasing amount of polymer might be result in decreased drug dissolve.

Physicochemical properties and bioavailability of carbamazepine polymorphs and dihydrate

The dissolution behaviors of carbamazepine (CZP) polymorphs and pseudopolymorphs (form I, form III and dihydrate) and the bioavailabilities (BA) of each form in dogs after oral administration were investigated. Bioavailability tests were carried out at a dose of either 40 mg/body or 200 mg/body. The results of dissolution tests in JP13 first fluid (pH 1.2) at 37°C indicated that the initial dissolution rate was in the order of form III>form I>dihydrate, while form III was transformed to dihydrate more rapidly than form I, resulting in decrease of the dissolution rate. The solubilities of both anhydrates (form I and form III), calculated from the initial dissolution rate of each anhydrate, were 1.5–1.6 times that of the dihydrate. At the dose of 40 mg/body, there were no significant differences in the area under the curve (AUC) between forms; their AUCs were nearly equal to that of CZP solution using polyethyleneglycol 400. These findings suggested that most crystalline powder of each form administered at the low dose was rapidly dissolved in gastrointestinal (GI) fluid. On the other hand, for the dose of 200 mg/body, significant differences in plasma concentration–time curves of CZP among polymorphic forms and dihydrate were observed. The order of AUC values was form I>form III>dihydrate. The inconsistency between the order of initial dissolution rates and that of AUC values at the high dose may have been due to rapid transformation from form III to dihydrate in GI fluids.

Quantitative determination of acrylate-based copolymer retarding layers on drug granules using pyrolysis–gas chromatography

A pyrolysis–GC (Py–GC) method for the quantitative determination of poly(ethylacrylate-methylmethacrylate) (PEAMMA) layers on granules for pharmaceutical use is described. The PEAMMA copolymer layer ensures a sustained release of the active agent after oral intake of the granules by the patient. Because of the substantial influence of the copolymer content on the kinetics of the drug release, a reliable method for the PEAMMA quantification had to be developed. The method includes a pre-treatment step, separating the PEAMMA layer from the granule matrix by its selective dissolution in acetone. Employing the pyrolytically formed monomers ethylacrylate and methylmethacrylate as the target compounds and by means of external calibration, the PEAMMA content of the drug granules was determined with a relative standard deviation of less than 5%. Finally, the Py–GC data obtained from different batches of granule material were compared with the corresponding results of kinetic dissolution tests. For one of six samples investigated a too fast drug release was found to correlate with a too low PEAMMA content.

Collaborative study on the development of a standard for evaluation of vibration levels for dissolution apparatus

This collaborative study in which seven laboratories participated was carried out in order to develop a dissolution standard for evaluating vibration levels for dissolution apparatus using enteric-coated granules of cefalexin (EG). Vibration levels for the dissolution apparatus were not dependent on whether the rotating basket (50 rpm) or paddle (50 rpm) methods were used. However, dissolution rates of cefalexin from EG were significantly increased by dissolution apparatus at high levels of vibration in the rotating basket method, while they were not affected by the variation in vibration levels in the paddle method. Dissolution apparatus could be divided into two groups according to their vibration levels and the dissolution test results by the rotating basket method at 50 rpm. The critical value of acceleration was about 0.05 m/s 2. The upper limit of normal dissolution rates of EG was calculated from the results of the rotating basket method at 50 rpm obtained from low vibration apparatus. All high vibration apparatus used in this study were distinguished by the confidence limit of the EG dissolution rate determined from low vibration apparatus. These results suggest that EG would be useful as a calibrator for detection of apparatus at high vibration levels.

Controlled-release coevaporates of dipyridamole prepared with acrylic polymers

The objective of this study was to obtain Controlled-release dosage forms of dipyridamole chosen as a model drug practically insoluble above pH 5. The coevaporates were prepared by the solvent method using enteric and insoluble acrylic polymers as well as their mixtures in different proportions. The in vitro dissolution test results were determined by the USP XXII paddle method at different pH values during a period of 8 h. These results showed that the progressive pH-dependent release of dipyridamole could only be achieved by blending enteric and insoluble polymers. To overcome the difficulty in maintaining sink conditions with the paddle method, the dissolution profiles of some of the formulations were investigated using the open flow-through cell method.

In VitroDissolution VersusIn VivoEvaluation of Four Different Aspirin Products

The single dose pharmacokinetic characteristics of four aspirin formulations in humans were compared with their in vitro dissolution properties. The pharmacokinetic parameters were determined by measuring salicylate concentrations in the plasma. Dissolution was measured by using the USP XX single time point dissolution test. The four aspirin products were a commercial tablet, a commercial capsule, a capsule filled with a commercial granulation, and a slow dissolving capsule formulation that failed the USP dissolution specification. It was found that there was a poor correlation between the in vitro dissolution results and the in vivo computed pharmacokinetic parameter statistics. In vivo testing in humans showed that all of the formulations were bioequivalent in terms of half-life and AUC, and the capsule that failed to pass the dissolution specification was bioequivalent to two of the three products that did pass the specification with respect to the maximum plasma concentration. None of the products could be demonstrated to be bioequivalent with regard to the time to maximum plasma concentration. However, none of the in vivo differences between the four aspirin formulations were judged to be clinically significant. Therefore, while there was a poor relationship between the in vitro USP XX dissolution test results and the bioequivalence test results, from a practical viewpoint the dissolution test is a satisfactory manufacturing quality control test, since it can detect differences in in vitro dissolution prior to their having a significant clinical impact.

Consumer vinegar test for determining calcium disintegration

A consumer test and standardized methods were compared for measuring the disintegration of calcium tablets, and the disintegration results were compared with results of dissolution testing to determine the ability of the consumer test of disintegration to predict bioavailability of calcium. Disintegration of 17 calcium supplement products, in tablet form, was studied in Simulated Gastric Fluid Test Solution, USP, without pepsin (GF), in distilled water, and in white distilled vinegar. For disintegration testing with GF and with distilled water, six tablets of each product were placed in an apparatus and immersed in the solution at 37 degrees C for 60 minutes. Six tablets of each product were tested in 200 mL of vinegar at room temperature for 30 minutes. Disintegration was determined by visual observation. Seven products were tested for dissolution in GF or water. Three samples of each product were tested at intervals over 120 minutes for calcium content. Results of testing with an ion-selective electrode were converted to milligrams and compared with the calcium content of the tablets (as claimed on the package label). The mean disintegration times of various calcium products in vinegar ranged from 1.8 to greater than 30 minutes. The mean time in distilled water and GF ranged from 1.6 to greater than 60 minutes and from 1.0 to greater than 60 minutes, respectively. Results were in agreement in 87% to 93% of cases between the consumer vinegar test and the standardized disintegration test methods, a significant correlation. No correlation was found between disintegration time and the extent of dissolution. The disintegration and dissolution of commercially available calcium tablets was highly variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of post treatment on nickel fluoride cold sealed finishes

SUMMARYThe performance of accelerated aged (post-treatment) nickel fluoride cold sealed finishes is compared with those of room temperature aged and conventional hydrothermal sealed finishes. It was found that accelerated ageing at temperatures of 60 and 80°C for 5–30 minutes in deionized water will improve the results of sealing quality tests of cold sealed anodized finishes, however it does not satisfy all the sealing quality tests applied to conventional hydrothermal sealed films. The results of acid dissolution and dye spot tests are acceptable for post-treated cold sealed films, and in general even better results than conventional hydrothermal sealing can be obtained with various metal salts used as post-treatment. Nevertheless, the admittance test was found to be difficult to satisfy and further ageing of 1–14 days was necessary to pass it. Such a problem was overcome by dual sealing, in which the cold sealed film was treated for a very short time (0.5min/μm) in boiling deionized water, resulting in...

The Release of Mercury from Dental Amalgam: The Mechanism and in vitro Testing

Dissolution of mercury from the Ag-Hg matrix phase of dental amalgam is distilled water and synthetic saliva, and the mercury evaporation from the solutions, were studied in vitro. The main objectives of the study were to evaluate the factors that affect the results of the mercury release tests, and to consider the possible mechanisms of the release in vivo. Specimens were exposed to the liquids in open or closed bottles, and the changes in the mercury concentration were determined by cold-vapor Atomic Absorption Spectrophotometry. Concentration vs. time tests showed the dissolution rate decreasing with time. Tests involving sequences of short and long exposures with solution changes showed higher average rates for short-term dissolution into the fresh solution than for the longer preceding exposures. The differences were attributed to a stifling effect of the concentration of elemental mercury on the dissolution. It is believed that mercury dissolved mainly in the elemental form and that a continuous increase in the concentration was made possible by oxidation in the solution. In open cells, some of the mercury was lost by evaporation. The analysis showed that the results of mercury dissolution tests depend on many test variables, such as time, solution volume, oxidation and evaporation conditions, etc. Evaporation, dissolution, and evaporation/dissolution mechanisms of the mercury release in vivo were considered. It was concluded that the dissolution/evaporation model best described the mercury release from dental amalgam restorations.

Gastric acidity dependent bioavailability of cinnarizine from two commercial capsules in healthy volunteers

Two commercially available capsules of 25 mg cinnarizine, which were chosen from the results of dissolution tests as the extreme cases out of 32 such capsules available in Japan, were examined in detail to determine their dissolution properties and bioavailabilities. The two capsules had similar dissolution rates at pH 1.2 and at pH 6.0 even though the rate at pH 1.2 was much faster than at pH 6.0. The serum levels of cinnarizine, which were determined by a GC-MS technique after administration of a single cinnarizine capsule, showed a wide variation in human volunteers, and this was ascribable to differences in the gastric acidity of the subjects. The AUC 0–8h values of the two capsules in the subjects having low gastric acidity were only 27 and 14% of those in the high acidity group, and the C max values of the two capsules were also depressed to 32 and 14% of those in the high acidity subject group, respectively. Bioavailability of cinnarizine appears to be determined mainly by the amount dissolved in the stomach.

Studies on Sustained Release II: in Vivo Performance of the Inert Matrix Sulfamethizole Tablet, Employing Polymethylmethacrylate

AbstractThe in vivo performance of the developed sustained release preparation was assessed on eight subjects. Based upon urinary excretion rates, in vivo data supported previous in vitro dissolution test results. An overall release/excretion rate of 32.6 mg/hr was obtained. The blood levels were assayed for intact drug and were fit to a three exponential equation employing the program AUTOAN. First order release rate constant of 1.33 hr was calculated, but the fits were not very satisfactory Although the blood levels were in an acceptable range, it is concluded that a faster releasing dosage form would be more appropriate This might require however, switching to another dosage form.

In vitro--in vivo correlation of dissolution, a time scaling problem? Transformation of in vitro results to the in vivo situation, using theophylline as a practical example.

Two principal approaches to demonstrating the continuous in vivo relevance of an in vitro dissolution test are outlined. The first uses the convolution technique to predict the concentration-time course in vivo; the second uses deconvolution as a mathematical tool to estimate the in vivo dissolution profile. The weighting function must be known to utilise either technique. Defined by the aim of the analysis the dose-normalized response to the oral solution is regarded as the weighting function (Impulse Response). In both cases the essential step is continuous comparison of the predicted time dependent data with actual readings of the same class. To permit the prediction of concentration-time data from in vitro dissolution data the basic equations for the transformation of the time base from in vitro to in vivo conditions are developed. The transformation is essential, since one cannot assume that the time scales for the in vitro and the in vivo experiment are definitely the same. The estimated in vivo dissolution profile using the deconvolution technique gives a hypothetical image of the true in vivo dissolution curve. Comparison with in vitro dissolution test results, using one of the equivalence testing procedures, reveals how closely and for how long the in vitro dissolution test simulates the in vivo dissolution process. For the formulation of theophylline studied, equivalence of the in vitro and the estimated in vivo dissolution profiles was not confirmed for the entire period of observation, but it was demonstrated for approximately the first 5 h. The later inequivalence is not due to possible non-linear or time-dependent kinetics of theophylline. There is a discussion of whether a change in pH, agitation of the formulation, diffusion conditions or the absorption rate constant along the gastrointestinal tract might explain the biphasic linear correlation of the in vitro and in vivo data observed.

Bioavailability of Commercial Ubidecarenone Tablets

In the previous paper (Jap. J. Hosp. Pharm., 9 (1), 14, 1983) it was reported that the commercially available ubidecarenone tablets showed various dissolution rates in the newly devised dissolution test, though they met the disintegration and content uniformity tests in J. P. X. In order to investigate the relationship between the results of such dissolution test and bioavailability of the tablets, 3 kinds of 10 mg ubidecarenone tablets, A-10-T1, A-10-T2, and B-10-SCT1 of which dissolution rates (min for T50) were high (0.5), medium (1.0) and low (10), respectively, were administered to healthy male subjects in dose of 2 tablets 3 times daily after meals for 8 to 14 days. Bioavailability of the tablets was evaluated on the basis of plasma levels of ubidecarenone (Ubiquinone-10, CoQ10).When compared by a cross-over experiment using 14 subjects, A-10-T1 and B-10-SCT1 increased plasma levels of CoQ10 to 1.87 and 1.13 times after 4 days, and to 2.20 and 1.20 times after 8 days as high as the control level. On the other hand, when A-10-T2 was administered to 9 subjects, plasma levels of CoQ10 were 1.44 times after 4 days, 1.70 times after 7 days, and 1.61 times after 14 days higher than those of the control. Thus, the increase of plasma levels of CoQ10 by these three tablets corresponded with their dissolution rates. Consequently, it was suggested that the dissolution test described in the previous report is useful for estimation of bioavailability as well as quality control of ubidecarenone tablets.