Rotating Basket Method Research Articles

Dissolution Testing of Norethindrone:Ethinyl Estradiol, Norethindrone: Mestranol, and Norethindrone Acetate: EthinyI Estradiol Cornbination Tablets

Dissolution of oral contraceptive combination products from six manufacturing firms was studied utilizing the rotating basket method at 100rpm in 600mL of 0.1M HCl and 0.02% sodium lauryl sulfate (SLS). Most of the combination products of norethindrone (NE):ethinyl estradiol (EE) dissolved satisfactorily in water using the paddle method which was first proposed by U.S.P., whereas three of 18 tested products showed better dissolution in acidic aqueous medium containing SLS. Acidic medium with surfactant was also found to be suitable for combination products of norethindrone (NE):mestranol (ME) and norethindrone acetate (NEAc):ethinyl estradiol (EE). A modified U.S.P. assay procedure, a reversed-phase high-performance liquid chromatographic (HPLC) method with a mobile phase of acetonitrile and phosphate buffer, was used to analyze NE and EE concurrently. The NEAc and ME were analyzed separately in these combination products. The NEAc was found to hydrolyze to some extent (~20% in 8 h) in acidic dissolution medium at room temperature, but less so at 4°C. The NE was identified as the sole degradation product of NEAc hydrolysis and was also measured to account for the total amount of NEAc dissolved. A simple dissoluting testing method which utilizes a single dissolution medium was applicable for all oral contraceptive combination tablets surveyed.

A Study on the Manufacture and in Vitro Dissolution of Terbutaline Sulfate Microcapsules and their Tablets

AbstractMicrocapsules of terbutaline sulfate with cellulose acetate butyrate and ethylcellulose were prepared using an emulsion-solvent evaporation technique. The in vitro dissolution of terbutaline sulfate was studied using the USP rotating basket method. As the polymer to drug ratio increased, the microcapsule size distribution shifted to the smaller size and the release of terbutaline sulfate decreased. The release of terbutaline sulfate was independent of the dissolution medium pH for both polymers. The release kinetics from the microcapsules was dependent on the polymer type and polymer to drug ratio. The release of terbutaline sulfate from cellulose acetate butyrate and ethylcellulose microcapsules formulated with a 1:1 polymer to drug ratio was complex and could not be differentiated between the square-root of time and first-order release models. However, the square-root of time model was followed by microcapsules formulated with a 2:1 or a 3:1 cellulose acetate butyrate to drug ratio. When the eth...

Influence of Sodium Lauryl Sulphate on Indomethacin Release Pattern from Zinc-Indcmethacin Complex and Indomethacin Capsules

AbstractA study was carried out to investigate the drug release pattern from zinc-indomethacin capsules with sodium lauryl sulphate (0. 25-1. 0% by weight of indomethacin) using the rotating basket method (USP XXI). The Drug release data failed to follow commonly used kinetic models that could explain the release pattern. Hence, the results were interpreted on the basis of bi-exponential, first-order kinetic model and found a good correlation between calculated and observed values. It showed that sodium lauryl sulphate enhanced both the faster and slower rate constants of the bi-exponential, first-order kinetic model and the percentage of the drug dissolved according to the faster process was increased. Indomethacin capsules with sodium lauryl sulphate showed also a similar release pattern.

Controlled Release Kinetics of Captopril From Tableted Microcapsules

AbstractDifferent viscosity grades ethylcellulose coated captopril microcapsules were prepared using temperature induced coacervation method from cyclohexane containing 2% Tween 80. Microcapsules were compressed directly into tablets. In vitro dissolution was carried out in 0.1 N HCl at 37°C using the rotating basket method. Release from tablets of all the batches was extensively prolonged in comparison to the respective microcapsules. The longest time for 70% drug release was shown by microcapsules (55min) and tablets (378 min) of the batch E-2. Release rate constants, correlation, determination and regression coefficients were calculated for the first-order, zero-order and Higuchi's equations. The best fit of release kinetics with the highest correlation and determination coefficients was achieved with the first-order followed by Higuchi's plot.

In vitro dissolution rates of six 8-methoxypsoralen formulations.

Dissolution rates in water of six oral 8-methoxypsoralen formulations were determined with both the rotating basket method and a column type flow-through method. Comparable and reproducible results were obtained with both methods. In view of the necessity in psoralen-UVA (PUVA) therapy that effective tissue concentrations of the drug be present in the skin during the irradiation period, we propose a requirement for a dissolution rate of 8-MOP tablets or capsules of at least 80% within 25 min. None of the three preparations registered in The Netherlands met this requirement. However, two preparations from abroad and a new capsule formulated in our pharmacy department with solid 8-MOP dispersed in polyethylene glycol 6000 showed satisfactory dissolution profiles.

Bioavailability Studies of Theophylline Ethylcellulose Microcapsules Prepared by Using Ethylene-Vinyl Acetate Copolymer as a Coacervation-Inducing Agent

The bioavailability of theophylline microcapsules prepared by using ethylene-vinyl acetate (EVA) copolymer as a coacervation-inducing agent was studied in rats. The dissolution rate of the microcapsules was determined by the rotating-basket and rotating-bottle methods. The higher the concentration of EVA copolymer used, the more sustained was the release of theophylline from the microcapsules. The mean maximum serum levels (Cmax) and time to maximum serum levels (tmax) were not significantly different for theophylline microcapsules prepared by a lower concentration of EVA copolymer (0 and 0.83%, respectively), compared with those for theophylline powder; whereas a significant difference was found when the higher concentration of EVA copolymer was used (> 1.7%). With regards to the area-under-the-curve (AUC) value, there was no significant difference between the theophylline powder and theophylline microcapsules. The elimination kinetics and the corresponding half-life (t1/2) were significantly different when the concentration of EVA copolymer was >3.3%. From the above results, it is evident that theophylline microcapsules prepared by using 3.3 and 5.0% EVA copolymer as the coacervation-inducing agent may act as sustained-release dosage forms. The correlation between the dissolution rate in vitro and the bioavailability in rats for theophylline microcapsules was investigated. The mean Cmax and tmax correlated well with the time taken to release 75% of the drug in vitro (t75%); however, the mean AUC showed no valid correlation with t75%. This implies that the dissolution rate correlated better with the rate of absorption (Cmaxtmax) than with the extent of absorption (AUC). Moreover, a linear relationship was also found between the time taken to release 50% of the microcapsules in vitro (t50%) and the time taken to absorb 50% of drug in vivo (Fab75%), indicating the presence of an in vitrocin vivo correlation. The Weibull function (td) was also used to evaluate the in vitrocin vivo correlation. It obviously indicates that td (in vitro) significantly correlated with td (in vivo) (rotating-basket method: r=0.9922; rotating-bottle method: r=0.9929). Thus, the results suggest that the theophylline microcapsules prepared by using EVA copolymer as a coacervation-inducing agent not only possess a sustained-release behavior, but also give a good correlation between in vitro dissolution rates and in vivo absorption.

ケトプロフェン坐剤の品質試験

The qualities of 2 suppositories (A and B) containing 75mg of Ketoprofen on the market were evaluated in the points of weight variation, content uniformity, and release from suppository bases. Release tests were made by the modified method of the rotating basket and the paddle method of J. P. X. In the paddle method, the suppository was put in the cellulose tube (the cellulose tube method) or in the net (the net method). The release fluid was phosphate buffer solution at pH 7.2.Following results were obtained: 1) The weight variations of both preparations were very small. 2) The content uniformities of both preparations were sufficient. 3) In the rotating basket method, the release of preparation A at 8 hours was about 50%, but that of B was about 20%. 4) In the cellulose tube method, the releases of both preparations at 8 hours were about 40%. 5) In the net method, the release of preparation A at 2 hours was about 100%, that of B at 4 hours was about 75%.

Release of Theophylline from Ethyl Cellulose Mecrocapsues Alone and in Conjuction with Fat Embedded (Precirol®) Granules and Hydroxypropyl Methycellulose

AbstractMicrocapsules of theophylline with ethyl cellulose were prepared by coacervation technique using cabosil® (silicon dioxide) as separant. Tablets were prepared from microcapsules, microcapsules + theophylline fat embedded granules, and microcapsules and hydroxypropyl methylcellulose 4000 (HPMC). Release was studied in vitro by the rotating basket method. Prolonged release of theophylline was observed from microcapsules with no drug dumping. The release from microcapsules was of first-order whereas that from all the tablet formulation was diffusion controlled according to the Higuchi model. Good correlation was found between release rate and core:wall ratio for all the systems. Decrease in hardness of tablets made from microcapsules alone decreased the release rate, indicating damage of microcapsules during compression. The tablets compressed from fat embedded granules, microcapsules with fat embedded granules, and microcapsules with HPMC gave a desired release for a 74 hour sustained release prepar...

Studies on Furosemide Tablets I Dissolutions of Commercial Products and Different Formulations

AbstractTablet properties of 3 different commercial brands of furosemide tablets from different marufacturers have been investigated. Their dissolution characteristics were determined by using USP rotating basket method and two different pH degrees as the test medium. At pH 4.6 a large variation in the dissolution rate of these brands was observed. The release rate differed from one lot to another.The effect of methods of tablet processing on furosemide release was also studied. A poor dissolution profile was observed with the tablet prepared by direct compression. The best result was obtained with the wet-granulation and the further study is extended on this process.

Bioavailability of sugar-coated tablets of thiamine disulfide in humans. II. Correlation with bioavailability in beagle dogs.

The bioavailabilities of six brands of thiamine disulfide (TDS) sugar-coated tablets were investigated in male beagle dogs and the correlations with the bioavailabilities in humans and the in vitro dissolution rates were investigated. the volume of water coadministered with the drug did not affect the bioavailability. The bioavailabilities of slow-dissolving products at pH 3-7.2 under the weakly destructive conditions of the paddle and rotating basket methods were relatively higher in dogs than in humans, which suggested a stronger disintegration force in dogs. Gastric fluid pH seemed to affect the in vivo dissolution of TDS itself. The in vivo parameters in dogs correlated significantly with the dissolution rate, disintegration time and in vivo parameters in high gastric acidity humans, with the exception of one product.

Studies on the Delivery Mechanisms of Theophylline from a Sustained Release Tablet

The in-vitro and in-vivo release of theophylline from an oral sustained release tablet (TheogradR) was studied.The in-vitro release profiles were determined by means of the rotating basket method, the paddle method and the modified disintegration method, described in the USP XX as apparatus 1, 2 and 3 respectively. Besides a stationary basket-rotating paddle method was used.It was demonstrated that in the stationary basket-rotating paddle apparatus and in the paddle apparatus at low rotational speeds of the paddle, mild agitation conditions were created. Under these conditions the release of theophylline from the sustained release tablet appeared to be matrix controlled. The leached matrix was found to be structurally very weak. For a matrix type of sustained release tablet this is probably beneficial as it would be less likely to cause accumulation and gastro-intestinal obstruction. In contrast the conditions of agitation in the rotating basket apparatus and in the disintegration apparatus were found to be rather severe. This was partly due to mechanical abrasion of the dosage form caused by the gauze of the basket and the basket-rack respectively, and partly the result of high solvent agitation, especially in the disintegration apparatus. Under these conditions it appeared that the empty matrix of the sustained release tablet eroded during the release process. This was confirmed by the results of studies under non-dissolving circumstances of the drug which showed that in this case only the leached matrix of the sustained release dosage form eroded and not that part of the dosage form from which the drug had not yet been dissolved. The in-vivo absorption appears to relate to the in-vitro release. When the Theograd tablet was taken on an empty stomach, it appeared that the absorption rate could succesfully be simulated by means of the stationary basket-rotating paddle method and the paddle method, both at low rotational speeds of the paddle. It was very likely that in this case the in-vivo release from the sustained release tablet was matrix controlled too. Under these conditions the bioavailability was found to be 65% compared with an oral solution of the drug. In contrast, when the Theograd tablet was taken after a meal, a relative bioavailability of 90% was observed. It was made plausible, that the greatly enhanced bioavailability, observed on postprandial administration of the tablet, was due to partial erosion of the leached matrix. This erosion was caused by the food induced increased motility of the gastro-intestinal tract. Based on the results of this study it is recommended to take TheogradR tablets after a meal.

Comparative Evaluation of Four Dissolution Apparatus

AbstractFour dissolution methods, the rotating basket, the rotating paddle, the rotating basket with paddle and the stationary basket-rotating paddle, were evaluated using capsules and non-disintegrating pellets of salicylic acid. The agitation intensity produced by the rotating basket method was very low and differed significantly throughout the vessel. However, it did not differ significantly at different positions in the stationary basket-rotating paddle method. This method offered considerable advantages and hence appears to be a suitable alternative to the existing compendial methods which have limitations for evaluation of dosage forms which tend to float on the dissolution medium.

The comparison of a novel continuous-flow dissolution apparatus for suppositories with the rotating basket technique

The dissolution rate of a drug from a solid dosage unit is an important parameter affecting drug bioavailability. Whjile dissolution testing has received much attention in the cases of tablets and capsules, it has received much less attention with suppositories. It was for this reason that the performance of a novel flow-through bead-bed apparatus was assessed in our laboratories. A flow-through dissolution chamber based on a published American design was constructed. It was tested in two ways: firstly using fatty based benzocaine suppositories, dissolution rates were determined at different temperatures. The data obtained agreed well with original published data indicating that the apparatus can be easily fashioned from standard laboratory equipaient and can give reproducible results in different laboratories. For comparison the benzocaine suppositories were also tested using a rotating basket method. Similar dissolution profiles Were obtained using the two methods at 37°C. Secondly the dissolution profiles of two commercially available indomethacin suppositories were measured using both the flow-through bead-bed apparatus and the more established rotating basket method. Although both products contained the same dose of indomethacin in a polyethylene glycol base, clear differences were noted between the dissolution profiles of the two products. The difference, however, was much more marked when using the flow-through bead-bed apparatus. These data therefore indicate that the latter technique may be a more precise tool for monitoring the effects of subtle formulation changes on dissolution profiles. In the case of indomethacin, from a pharmacological standpoint, a slower release rate is advantageous as such a product is likely to be more effective at relieving early morning stiffness after an evening dose.

Dissolution Rates of Commercial Phenylbutazone Tablets: Inter-And Intra-Brand Effects

A study has been carried out to investigate the dissolution rate profiles of twelve batches of sugar-coated phenylbutazone tablets belonging to four commercial brands. Using the rotating basket method, significant inter-brand and inter-batch variations in dissolution rates were found. Only two batches of one brand passed the B.P. dissolution limit whilst other batches had percentages dissolution between 0.3 and 58 after 45 min. Batches with poor dissolution characteristics exhibited significant tablet-to-tablet variations in dissolution rates; a finding which was not observed in the relatively fast-dissolving batches. When the paddle method was substituted for the B.P. basket method, the dissolution rates were relatively faster but similar dissolution failure was found. However, the tablet-to-tablet dissolution variability was decreased in some of the batches. The observed differences in dissolution rates of the batches examined were unrelated to their disintegration times. Inspite of the poor dissolution characteristics of most of the batches studied, no apparent chemical degradation was found. It is recommended that when evaluating the dissolution rates of brands of phenylbutazone tablets, a number of batches from each brand should be tested.

Dissolution of Commercial Phenytoin Products

The in vitro dissolution rate of 3 commercial phenytoin (PHT) products with different particle sizes (PHT A-1, A-2 from manufacturer A, and PHT B from manufacturer B) was examined by USP rotating basket method. The difference of the dissolution rate was due to the difference in particle sizes. Particularly in the 1st fluid, 2nd fluid and borate buffer with 0.1% Polysorbate 80, the dissolution rate was significantly enhanced in the order of PHT A-l<PHT A-2< PHT B. The quantity of Polysorbate 80 was related to the dissolution rate of PHT B, but not of PHT A-1 and PHT A-2. These findings should have resulted from the difference in the pharmaceutical factors.

Sustained Absorption does not Necessarily Reduce the Systemic Availability of Propranolol

The in vitro dissolution and in vivo pharmacokinetics of two marketed long-acting propranolol formulations, Duranol (D) and Inderal LA (LA) were examined. Dissolution rates were obtained using the USP rotating basket method, while the relative bioavailabilities of the products were evaluated in normal volunteers under single-dose (6 subjects) and steady-state (11 subjects) conditions in two separate crossover studies. Both LA and D demonstrated pH-independent dissolution profiles with T50 values of 4 and 6 hours, respectively. While the dissolution profile for D was sigmoidal and complete in 12 hours, data for LA suggested a log-linear profile and indicated only 85% dissolution at 12 hours. In pharmacokinetic studies the tmax was achieved in 7 to 8 hours for both products; however, Cmax values for D vs LA were 80.4 vs 49.9 ng/ml (p < 0.05) after a single dose and 76.6 vs 52.6 ng/ml (p < 0.01) at steady-state drug administration. The bioavailability of D was 55% and 44% greater than that of LA during single-dose and steady-state studies, respectively. Intersubject variability was lower for D than for LA during both studies. The data indicate that sustained absorption does not necessarily reduce the systemic availability of propranolol, and suggest that formulation-related factors may contribute to the low bioavailability of LA. The superior bioavailability and lower intersubject variability achieved with D compared to LA suggest that D should be at least as effective as LA in the treatment of cardiovascular disorders.

Quality Test of Medazepam Tablets

The quality of five brands (A to E) of sugar-coated tablets containing 5 or 10 mg of medazepam was studied in terms of pharmaceutical properties. Although all the products tested met the requirements for the disintegration test according to J.P. IX, the disintegration time of Product D was 3 to 4 times longer than those of the other products. In the dissolution test, the results obtained by the rotating basket method were similar to those by the paddle method. A good correlation was noted between the dissolution rate and the disintegration time. The dissolution rates of four brands reached about 100% within 30 minutes, except the rate of Product D which was only 7% even after 60 minutes, possibly due to obstruction of the dissolution by the layer of sugar coating.

Crystal defects and dissolution

Potassium perchlorate crystals were grown in silica gel by reaction between perchloric acid in the gel and potassium chloride diffusing into the gel from a layer of solution on the gel surface. The crystals were harvested at depths from the surface of 0–1, 2–3, 4–6 cm. X-Ray diffraction and DSC thermograms showed that the crystals were identical and no impurities were detected by X-ray energy analysis. Octahedral crystals were selected, cleaved to expose the (001) plane and etched with a mixture of sodium sulfite and sulfuric acid. The dislocation etch pits were counted under surface illumination using a differential interference contrast microscope. Dislocation densities were approximately normally distributed with the mean densities being greatest at the 0–1 cm level where the growth rate was fastest and lowest at the 4–6 cm growth level where the growth rate was slowest. Bulk dissolution measurements, carried out under sink conditions in 95% ethanol using the USP rotating basket method, showed a positive correlation between the observed dissolution rate constant, K' obs, and the dislocation density. Dissolution rates increased with the number of dislocations such that an approximately 3-fold increase in mean dislocation density produced a 21% increase in K' obs.

Quality Test of Commercial Spironolactone Tablets

The quality of 5 kinds of commercial spironolactone tablets was evaluated by several tests, such as dissolution, weight variation, content, content uniformity, disintegration and hardness. 2 kinds of apparatus were used in dissolution test: one described in U. S. P. XIX (rotating basket method) and the other in U. S. P. XX (paddle method). 50% dissolution time (T50) differed amo ng samples tested, where the times by rotating basket method were from 3.9 to 120 min or longer and those by paddle method were from 3.6 to 28.2 min., The difference of the apparatus on the dissolution test has an influence on the dissolution rate and T50, whereas T50 of the high dissolution rate samples was nearly equal by either method, but of the low rate samples it was smaller by paddle method than by rotating basket method. Weight variation was 0.6-2.0%, while the disintegration time was less than 7.9 min. Those tests met the requirements in J. P. IX. The content was 98-101% which was within the U. S. P. limits (95-105%), while the content uniformity also satisfied the U. S. P. limits. The hardness was 2.1-7.7kg/cm2.

Pharmaceutical Tests and Plasma Theophylline Level of Slow-Release Preparation

Plasma theophylline concentration of a slow-release theophylline preparation (SRT: Theona P) was measured by high-pressure liquid chromatography. SRT was administered to 6 healthy adults orally in dose of 100mg. Dissolution test of SRT by the rotating basket method made in accordance with U. S. P. XVIII revealed that the drug tended to dissolve slowly, dissolution rate being about 50% 6 hours after initiation of the experiment. The experiment also demonstrated that plasma concentration of theophylline reached peak about 5 hours after oral administration of SRT on the average, and about 2 hours after use of Aminophylline Tablet (immediate-release preparation).Average maximal plasma theophylline level was 1.32μg/ml for SRT as compared with 1.92μg/ml for Aminophylline. In clinical trial, the plasma concentration of theophylline was not maintained at 10μg/ml after oral administration of SRT and Aminophylline Tablet in dose of 100mg 4 times a day, respectively. The 10-μg/ml level was maintained when SRT single dose was increased to 200mg.