Evaluation of the Performance of Prednisone and Salicylic Acid Usp Dissolution Calibrators

Achanta, A. S.; Gray, Vivian A.; Cecil, Todd L.; Grady, Lee T.

doi:10.3109/03639049509026666

Cited by 16 publications

(13 citation statements)

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“…The same authors suggested that the round bottom of a dissolution vessel, in combination with stirring devices (eg, paddle), results in varied flow dynamics within the vessel, which appears to be the cause of observed high variability in the testing. [20][21][22] The CFD-predicted fluid velocities above provide substantial support for such speculation.…”

Section: Velocity Contours Directly Below the Paddlementioning

confidence: 85%

Simulating the hydrodynamic conditions in the united states pharmacopeia paddle dissolution apparatus

et al. 2003

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KEYWORDS: computational fluid dynamics (CFD), USP paddle apparatus, dissolution, hydrodynamics, modeling The objective of this work was to examine the feasibility of developing a high-performance computing software system to simulate the United States Pharmacopeia (USP) dissolution apparatus 2 (paddle apparatus) and thus aid in characterizing the fluid hydrodynamics in the method. The USP apparatus was modeled using the hydrodynamic package Fluent. The Gambit program was used to create a "wireframe" of the apparatus and generate the 3-dimensional grids for the computational fluid dynamics solver. The Fluent solver was run on an IBM RS/6000 SP distributed memory parallel processor system, using 8 processors.Configurations with and without a tablet present were developed and examined. Simulations for a liquidfilled vessel at a paddle speed of 50 rpm were generated. Large variations in fluid velocity magnitudes with position in the vessel were evident. Fluid velocity predictions were in good agreement with those previously published, using laser Doppler velocity measurements. A low-velocity domain was evident directly below the center of the rotating paddle. The model was extended to simulate the impact of the presence of a cylindrical tablet in the base of the dissolution vessel. The presence of the tablet complicated the local fluid flow, and large fluid shear rates were evident at the base of the compact. Fluid shear rates varied depending on the tablet surface and the location on the surface and were consistent with the reported asymmetrical dissolution of model tablets. The approach has the potential to explain the variable dissolution results reported and to aid in the design/prediction of optimal dissolution conditions for in vitro-in vivo correlations.

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Section: Velocity Contours Directly Below the Paddlementioning

confidence: 85%

Simulating the hydrodynamic conditions in the united states pharmacopeia paddle dissolution apparatus

et al. 2003

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“…Parameters in this group are incidental vibration, the extent of degassing, inconsistent tablet placement in vessels, and inconsistent use of clips or sinkers (3,(11)(12)(13). The third class of variability comes indirectly from performance differences in calibrator tablets that are real (8,16,17), operator induced, or from excipient deposition (18). As the name implies, calibrator tablets are used to verify overall system precision to qualify apparatus and control system variability.…”

Section: Challengesmentioning

confidence: 99%

The Science of USP 1 and 2 Dissolution: Present Challenges and Future Relevance

Gray¹,

et al. 2009

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Since its inception, the dissolution test has come under increasing levels of scrutiny regarding its relevance, especially to the correlation of results to levels of drug in blood. The technique is discussed, limited to solid oral dosage forms, beginning with the scientific origins of the dissolution test, followed by a discussion of the roles of dissolution in product development, consistent batch manufacture (QC release), and stability testing. The ultimate role of dissolution testing, "to have the results correlated to in vivo results or in vivo in vitro correlation," is reviewed. The recent debate on mechanical calibration versus performance testing using USP calibrator tablets is presented, followed by a discussion of variability and hydrodynamics of USP Apparatus 1 and Apparatus 2. Finally, the future of dissolution testing is discussed in terms of new initiatives in the industry such as quality by design (QbD), process analytical technology (PAT), and design of experiments (DOE).

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“…Several reports in the literature have suggested that there is considerable variability, unpredictability and randomness in dissolution profiles using the paddle dissolution apparatus, even for dissolution apparatus calibrator tablets. [1][2][3][4][5][6] Dissolution of most drugs is diffusion controlled 7 and, consequently, the mass transfer of such drugs in a stirred vessel is dependent on fluid flow, ie, forced convection. [8][9][10] Many solid dosage forms disintegrate into smaller fragments and particles during the course of the dissolution test, and the particles decrease in size as dissolution proceeds.…”

Section: Introductionmentioning

confidence: 99%

Computational fluid dynamics modeling of the paddle dissolution apparatus: Agitation rate, mixing patterns, and fluid velocities

et al. 2004

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The purpose of this research was to further investigate the hydrodynamics of the United States Pharmacopeia (USP) paddle dissolution apparatus using a previously generated computational fluid dynamics (CFD) model. The influence of paddle rotational speed on the hydrodynamics in the dissolution vessel was simulated. The maximum velocity magnitude for axial and tangential velocities at different locations in the vessel was found to increase linearly with the paddle rotational speed. Path-lines of fluid mixing, which were examined from a central region at the base of the vessel, did not reveal a region of poor mixing between the upper cylindrical and lower hemispherical volumes, as previously speculated. Considerable differences in the resulting flow patterns were observed for paddle rotational speeds between 25 and 150 rpm. The approximate time required to achieve complete mixing varied between 2 to 5 seconds at 150 rpm and 40 to 60 seconds at 25 rpm, although complete mixing was achievable for each speed examined. An analysis of CFDgenerated velocities above the top surface of a cylindrical compact positioned at the base of the vessel, below the center of the rotating paddle, revealed that the fluid in this region was undergoing solid body rotation. An examination of the velocity boundary layers adjacent to the curved surface of the compact revealed large peaks in the shear rates for a region within ~3 mm from the base of the compact, consistent with a 'grooving' effect, which had been previously seen on the surface of compacts following dissolution, associated with a higher dissolution rate in this region.

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Evaluation of the Performance of Prednisone and Salicylic Acid Usp Dissolution Calibrators

Cited by 16 publications

References 0 publications

Simulating the hydrodynamic conditions in the united states pharmacopeia paddle dissolution apparatus

Simulating the hydrodynamic conditions in the united states pharmacopeia paddle dissolution apparatus

The Science of USP 1 and 2 Dissolution: Present Challenges and Future Relevance

Computational fluid dynamics modeling of the paddle dissolution apparatus: Agitation rate, mixing patterns, and fluid velocities

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