Design and Evaluation of a Rotating Basket-Paddle Dissolution Apparatus

Abstract

The rotating basket-paddle dissolution apparatus is a combination of the USP/NF rotating basket and rotating paddle. A comparative dissolution study was performed utilizing this new apparatus and the two USP/NF apparatus at various stirring speeds using non-disintegrating oxalic acid tablets and disintegrating aspirin tablets. The amount of drug released using the new apparatus was significantly higher than the rotating basket but significantly lower than the rotating paddle at each of the stirring speeds studied. The results obtained using this new apparatus were highly reproducible compared to the USP/NF apparatus.     

Evaluation of In Vitro/In Vivo Correlation Utilizing a Rotating Basket-Paddle Dissolution Apparatus

Abstract

The desirability of good correlations of parameters derived from in vitro dissolution study with parameters derived from in vivo bioavailability study is well established in biopharmaceutics. Reports on several in vitro dissolution apparatus, including the two official USP/NF methods, have appeared in the literature over the years. However, none have been accepted as universal because each apparatus is useful only for the dissolution testing of a specific group of drugs or dosage forms. Comparative dissolution testing was performed using the rotating basket-paddle apparatus and the two official USP/NF apparatus.

A comparative bioavailability study was carried out on four batches of rapidly disintegrating tablets (Formulations A to D) of nitrofurantoin and perphenazine using rabbit as an animal model. Excellent rank order (qualitative) correlations were observed among all combinations of in vitro and in vivo parameters. With the drug nitrofurantoin, an excellent quantitative correlation was found between the dissolution halftime and Cmax or Tmax or AUC. Yet, a repeated run with perphenazine yielded excellent correlation between dissolution halftime and Cmax or Tmax, but poor correlation between dissolution halftime and AUC.     

Evaluation of In Vitro/In Vivo Correlation Utilizing a Rotating Basket-Paddle Dissolution Apparatus

The desirability of good correlations of parameters derived from in vitro dissolution study with parameters derived from in vivo bioavailability study is well established in biopharmaceutics. Reports on several in vitro dissolution apparatus, including the two official USP/NF methods, have appeared in the literature over the years. However, none have been accepted as universal because each apparatus is useful only for the dissolution testing of a specific group of drugs or dosage forms. Comparative dissolution testing was performed using the rotating basket-paddle apparatus and the two official USP/NF apparatus.

A comparative bioavailability study was carried out on four batches of rapidly disintegrating tablets (Formulations A to D) of nitrofurantoin and perphenazine using rabbit as an animal model. Excellent rank order (qualitative) correlations were observed among all combinations of in vitro and in vivo parameters. With the drug nitrofurantoin, an excellent quantitative correlation was found between the dissolution halftime and Cmax or Tmax or AUC. Yet, a repeated run with perphenazine yielded excellent correlation between dissolution halftime and Cmax or Tmax, but poor correlation between dissolution halftime and AUC.     

Comparative Evaluation of Four Dissolution Apparatus

Four 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.     

Comparative Evaluation of Four Dissolution Apparatus

Abstract

Four 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.     

Suppository Dissolution Testing: Apparatus Design and Release of Aspirin

Present methods of in vitro dissolution testing for suppositories were found to be lacking in universal acceptance, reproducibility, and difficult to perform. Initially a USP basket for tablet dissolution with one-hundred milliliters of phosphate buffer of pH 8 to approximate rectal pH was used. A slow constant stirring speed was maintained by means of a Hanson dissolution drive control and hollow spindle-stirrer apparatus as well as a constant temperature of 37.5±0.1° Aspirin in polyethylene glycol bases gave plausible, reproducible results with this apparatus. However, oil bases (i.e. cocoa butter) gave unacceptable, irreproducible results since the base blocked the openings of the basket mesh. This report describes a modified basket method where the basket is polyurethane of the same size and configuration as the USP basket. The basket described has twelve linear vertical slots of 0.25 mm width allowing for a porosity of 52%. Results of aspirin release from four PEG bases prepared in this laboratory are presented and discussed. The results were reproducible. Five commercially available suppositories were also tested in the above described manner.

Dissolution, or drug release has been extensively studied and reported for only a few selected tablets and other oral solid dosage forms. Dissolution has been shown to be the best in vitro parameter to correlate release of drug to bioavailability. Dissolution of drug from non-oral dose forms however, has not been extensively investigated. Past research into drug release from suppository bases has taken a number of approaches, some of which are not very scientifically sound or reproducible. Gibaldi and Gundhofer in 1975 studied bioavailability of aspirin from commercially available suppositories (1). These researchers reported “the rate of absorption of aspirin was sufficiently slow to raise considerable doubt as to whether efficaceous body levels of aspirin or salicylate are obtained after a single dose” (1). Other reports also question the absorption of aspirin from suppositories (2, 3).

Because present methods of in vitro dissolution testing appeared lacking in universal acceptance and reproducibility or were difficult to perform, this study was undertaken to develop an apparatus for suppository dissolution. To test the reproducibility of the devised method, four PEG base blends were used as vehicle for aspirin. Several commercially available products were also tested to determine their release patterns.     

Evaluation of an in Vitro Dissolution and Permeation Apparatus for Oral Solid Pharmaceutical Dosage Forms

An apparatus based in the USP dissolution test, the F-C-SL apparatus (Ferreira-Costa-Sousa Lobo), was developed that allowed the simultaneous evaluation of the in vitro release and permeation of oral solid pharmaceutical dosage forms. The release rate in both dissolution devices (USP and F-C-SL apparatus) was evaluated with acetaminophen tablets. Different test conditions (stirring rate and solvent volume ratio) were investigated and no significant differences in acetaminophen release rate were found between these apparatuses. In the F-C-SL apparatus, the in vitro permeation kinetics of acetaminophen were evaluated using synthetic membranes and followed a zero-order kinetic.     

Evaluation of a Modified Paddle Method for Dissolution Testing

A modification of the U.S.P. paddle method for dissolution was evaluated. A 10-mesh size circular stainless steel screen was placed at the bottom of the dissolution vessel establishing an elevated platform for the tablet. The modified method was compared with the U.S.P. paddle and basket methods utilizing three different tablet formulations of the nondisintigratiny type. Two tablet formulations contained a gel forming material hydroxypro-pylmethylcellulose K-4000 and the third tablet formulation has tricalcium phosphate as the major filler. The active ingredients were either dyphylline or melperone HCl. The data were evaluated by a one-way analysis of variance combined with Ryan-Einot-Gabriel-Welsch multiple F-test for comparison between methods. The results suggest that the proposed modified paddle method for dissolution may provide the formulator with an alternative for evaluating release of drugs from solid dosage forms containing swell able gums. This method offers the advantages of continuous visual monitoring of the dosage form to ascertain its integrity and full exposure of the total surface area of the tablet without sticking to the walls of the dissolution vessel     

Evaluation of a Modified Paddle Method for Dissolution Testing

Abstract

A modification of the U.S.P. paddle method for dissolution was evaluated. A 10-mesh size circular stainless steel screen was placed at the bottom of the dissolution vessel establishing an elevated platform for the tablet. The modified method was compared with the U.S.P. paddle and basket methods utilizing three different tablet formulations of the nondisintigratiny type. Two tablet formulations contained a gel forming material hydroxypro-pylmethylcellulose K-4000 and the third tablet formulation has tricalcium phosphate as the major filler. The active ingredients were either dyphylline or melperone HCl. The data were evaluated by a one-way analysis of variance combined with Ryan-Einot-Gabriel-Welsch multiple F-test for comparison between methods. The results suggest that the proposed modified paddle method for dissolution may provide the formulator with an alternative for evaluating release of drugs from solid dosage forms containing swell able gums. This method offers the advantages of continuous visual monitoring of the dosage form to ascertain its integrity and full exposure of the total surface area of the tablet without sticking to the walls of the dissolution vessel     

A Critical Assessment of the Usp Dissolution Apparatus Suitability Test Criteria

This report describes results of a survey conducted to assess the variability in drug release from the USP calibrators and its dependence on various deaeration methods. The calibrator data submitted by 33 laboratories, involved tests of 1659 sets (6 or 12 tablets/set) from four lots of prednisone and salicylic acid each, using apparatuses 1 & 2 run at 50 and 100 rpm. Overall variabilityranges for the individual sets, which met the USP dissolution apparatus Suitability Criteria, were 0.5-31.3% for prednisone/apparatus 1, 0-13.2% for salicylic acid/apparatus 1, 0.3-10.2% for prednisone/apparatus 2 and 0.7-20.2% for salicylic acid/apparatus 2. The results of this survey suggest that variability levels are dependent on apparatus/calibrator combination. Although deaeration of dissolution media tends to reduce the failures i.e. not meeting the Suitability Criteria, its effect on reducing the variability appears to be minimal. Among the various deaeration methods reported, degassing the media by a combination of heating with helium sparging or with filtering under vacuum tend to give the lowest failure rate. From our findings, a variability of up to 31% CV (coefficient of variation) in percent drug release for the calibrator can occur with the samples still meeting the USP criteria. However, if the apparatus/calibrator combination is taken into consideration with appropriate deaeration method, the maximum expected variability can be reduced to 10% or less. The results of this survey show that rather than an eight point dissolution calibration test criteria, a four point evaluation system i.e. testing non-disintegrating tablets with apparatus 1 and disintegrating tablets with apparatus 2 may provide sufficient information for system suitability. It is also recommended that a similar formulation/apparatus combination should be considered for drug products evaluation which might yield less variable results with an improved potentials of in vitro/in vivo correlations particularly for modifieddrug release products.     

An Evaluation of Smecta as a Tablet Disintegrant and Dissolution Aid

Smecta is a nonfibrous Attapulgite (NFA), mostly composed of smectite. It was evaluated as a disintegrant in tablets made by direct compression as well as by wet granulation and using lactose and dicalcium phosphate as water soluble and water insoluble fillers, respectively. An inorganic clay, magnesium aluminum silicate (Veegum), a modified starch (Starch 1500), a cross-linked carboxymethyl cellulose (Ac-Di-Sol), and a cross-linked polyvinylpyrrolidone (Polyplasdone XL) were used for comparative evaluation. Smecta performed well as a disintegrant in tablets made by either method. It was superior to Veegum and Starch 1500, but inferior to Ac-Di-Sol and Polyplasdone XL. In tablets with Smecta, dissolution of hydrochlorothiazide (HCTZ) was superior to those with Ac-Di-Sol.     

An Evaluation of Smecta as a Tablet Disintegrant and Dissolution Aid

Abstract

Smecta is a nonfibrous Attapulgite (NFA), mostly composed of smectite. It was evaluated as a disintegrant in tablets made by direct compression as well as by wet granulation and using lactose and dicalcium phosphate as water soluble and water insoluble fillers, respectively. An inorganic clay, magnesium aluminum silicate (Veegum), a modified starch (Starch 1500), a cross-linked carboxymethyl cellulose (Ac-Di-Sol), and a cross-linked polyvinylpyrrolidone (Polyplasdone XL) were used for comparative evaluation. Smecta performed well as a disintegrant in tablets made by either method. It was superior to Veegum and Starch 1500, but inferior to Ac-Di-Sol and Polyplasdone XL. In tablets with Smecta, dissolution of hydrochlorothiazide (HCTZ) was superior to those with Ac-Di-Sol.     

Design of a Rotating Cryostat to Minimise Vibrational Heating

One of the challenges facing physicists wishing to experiment at temperatures of 1 rnK or below is to reduce vibrational heating in their cryostat. Vibrational heating limits cold time and reduces temperature stability. Many techniques are employed, however, one of the more effective is to isolate the cryostat using air springs. We describe the resugts of fitting air springs to the Manchester rotating cryostat, to our knowledge the first such fitting on any rotating cryostat. The modification has enabled an experiment to be carried out that required long periods of time with a constant temperature. The experiment could be held at 2 mK for up to 4 weeks with 30% of its time spent rotating. We describe other modifications to our rotation system that have reduced the required maintenance and improved the smoothness of the rotation and present data showing how vibrational and heating effects vary with rotation speeds up to 0.24 Hz.     

Experimental Design in Dissolution Testing

Abstract

Comparison of dissolution profiles may be facilitated by blocking the individual units of a given batch, thus greatly reducing the possibility of error from variation between experimental runs. Experimental designs are described which allow valid comparisons to be made between batches, as well as allowing the between run variation to he assessed and identifying any systematic errors resulting from differences between vessels. The number of tests reguired may freguently be reduced, and the need for replicate testing eliminated. The limitation of 6 vessels per run imposes certain restrictions in the experimental designs possible. Applications of these experimental designs in characterisation of dosage forms by their pH-dissolution topography and their use in factorial formulation experiments are described.     

Experimental Design in Dissolution Testing

Comparison of dissolution profiles may be facilitated by blocking the individual units of a given batch, thus greatly reducing the possibility of error from variation between experimental runs. Experimental designs are described which allow valid comparisons to be made between batches, as well as allowing the between run variation to he assessed and identifying any systematic errors resulting from differences between vessels. The number of tests reguired may freguently be reduced, and the need for replicate testing eliminated. The limitation of 6 vessels per run imposes certain restrictions in the experimental designs possible. Applications of these experimental designs in characterisation of dosage forms by their pH-dissolution topography and their use in factorial formulation experiments are described.     

Dissolution Behaviour of Indomethacin Capsule Formulations: Comparison of Two Types of Usp Apparatus

Abstract

The dissolution behaviour of indomethacin from six commercial brands of indomethacin capsules, using the USP rotating basket apparatus and the USP paddle apparatus have been studied. The products showed marked differences in their dissolution profiles. The dissolution rates have been different in different brands, and variation has also been observed depending on the method of testing used. The rotating basket apparatus showed superior discriminating capacity than the paddle method.     

射线数字成像检测仪的光电系统设计

设计了射线数字成像检测仪的光电系统,包括转换屏、光路、CCD相机以及计算机处理电 路等。采用CsI(Tl)单晶闪烁体将X射线图像转换为可见光图像,用科学级CCD将光图像转换为电信号,利用计算机并行口对图像进行采集. 实验结果证明图像质量优于像增强器组成的成像系统,适用于要求高质量成像检测的场合。     

The Evaluation of Pressure Under Heating in a High Pressure Apparatus

The possibility of high pressure evaluation at high temperature in the anvil type high pressure apparatus (HPA), is analyzed by a simple model. It is shown that at a certain moment after HPA loading the deformation of the compressible gasket may be described by equations for the elastic strains of matter, particularly by the Murnaghan equation. The latter can be used for high pressure evaluation by the measurement of gasket thickness. Some experimental data in the range of P-T parameters 3.5–4.5 GPa and 1300–1500 K are cited as examples of utilizing this high pressure evaluation method.     

微机电子衡器设计

本文介绍了微机电子衡器的组成,并对其软硬件设计进行了论述.