Design and characterization of a laminar flow-through dissolution apparatus: Comparison of hydrodynamic conditions to those of common dissolution techniques

Abstract

A flow-through dissolution apparatus was designed and evaluated to screen small quantities of pharmaceutical drug compounds early in development. The apparatus was designed to mount on a microscope slide such that a compacted solid drug was positioned flush along one wall and the fluid flow in the apparatus was laminar flow in a rectangular duct. Stereomicroscopic digital images and Raman spectra of the solid were taken during dissolution and the effluent dissolution medium was collected in fractions to determine the dissolution rate by fluorescence or HPLC/UV. Three compounds, triamterene, ketoprofen, and β-naphthoic acid were investigated in the dissolution flow cell at various hydrodynamic conditions. In conditions where no solvent-mediated conversion was expected, there was a decrease in dissolution rate with time in the flow through cell that was associated with surface smoothing. This phenomenon also occurred in rotating disk experiments. In either case, the magnitude and time course of the decrease in dissolution rate with time is generally different enough to distinguish from the decrease in dissolution rate due to solvent-mediated conversion.

Keywords::

• Dissolution apparatus
• solution-mediated phase transformation
• flow-through
• rotating disk
• Raman
• salt form

Acknowledgments

The authors would like to acknowledge Szymon Chawarski for his involvement in the design and fabrication of the dissolution apparatus. The authors would also like to thank Dr Manish Gupta and Dr Richard Winnike for their input in this project. T. Bergman wishes to acknowledge and thank the U.S. National Science Foundation for support of this activity.

Appendix I

Shear rate and shear stress analysis: Rotating disk

Shear stresses in cylindrical coordinates are defined as:^[7]

where, τ, is the shear stress in the radial, r, tangential, φ, and axial, y, directions and μ is the viscosity. For rotating disk the velocity, v, for each direction:^[14]

where, r, is the radius, ω is the rotation speed, y is the axial location and ν is the kinematic viscosity. The derivatives of the velocity components (Equations 13–15) are substituted into the shear stresses in Equations 10–12 to yield the shear stress at the surface y = 0:

The magnitude of the tensor is:^[7]

Equations 16–18 are substituted into Equation 19 to find the average shear stress as a function of r on the disk surface at y = 0:

The average stress along the surface of the entire compact is the average of the stress over the entire range, r.

resulting in:

The average shear rate at the disk surface, is the average stress divided by –μ.

Appendix II

Derivation of relationship between rotation speed in a rotating disk apparatus and volumetric flow rate in the dissolution flow cell

Flux of a drug from a rotating disk is described as:^[14]

The dissolution rate for a drug compact in a rectangular channel is:^[26]

To convert this into a flux, divide by area.

When we equate the fluxes in Equation 1 and Equation 3, solve for ω1/2 we obtain the relationship:

The flow cell tablet area, A, used in this study was 6.8 × 10⁻⁶ m².