Dissolution rate agitation

These mixing motions will tend to improve drug absorption for two reasons. Any factor that increases rate of dissolution will increase the rate (and possibly the extent) of absorption, especially for poorly water-soluble drugs (BCS Classes II and IV). Since rate of dissolution depends on agitation intensity, mixing movements will tend to increase dissolution rate and thereby influence absorption. As rate of absorption depends directly on membrane surface area, and since mixing increases the contact area between drug and... 

M Bisrat, C Nystrom. Physicochemical aspects of drug release. VIII. The relation between particle size and surface specific dissolution rate in agitated suspensions. Int J Pharm 47 223-231, 1988. 

P. J. Niebergall, G. Milsovich, J. E. Goyan. Dissolution rate studies. II. Dissolution of particles under conditions of rapid agitation. J. Pharm. Sci. 1963, 52, 236-241. 

The drug dissolution rate could be determined by dispersing the powder in a test medium under suitable agitation or by studying the dissolution for a constant surface area by using the rotating-disc method (Fig. 21.6). The latter method should be the technique of choice, except when studies of the effect of particle size are of... 

The rate of agitation, stirring, or flow of solvent, if the dissolution is transport-controlled, but not when the dissolution is reaction-con-trolled. Increasing the agitation rate corresponds to an increased hydrodynamic flow rate and to an increased Reynolds number [104, 117] and results in a reduction in the thickness of the diffusion layer in Eqs. (43), (45), (46), (49), and (50) for transport control. Therefore, an increased agitation rate will increase the dissolution rate, if the dissolution is transport-controlled (Eqs. (41 16,49,51,52), but will have no effect if the dissolution is reaction-controlled. Turbulent flow (which occurs at Reynolds numbers exceeding 1000 to 2000 and which is a chaotic phenomenon) may cause irreproducible and/or unpredictable dissolution rates [104,117] and should therefore be avoided. 

The intrinsic dissolution rate was determined after compressing powder under 2000 p.s.i.g. pressure using 3/8" diameter disc-shaped dies. In one liter of O.lAf hydrochloric acid at 37°, agitated at a rate of 50 r.p.m., the intrinsic dissolution rate of halcinonide is 8.33 x 10 ... 

Ramtoola Z, Corrigan 01. Effect of agitation intensity on the dissolution rate of indomethacin and indomethacin-citric acid compressed discs. Drug Dev Ind Pharm 1988 14(15-17) 2241-2253. 

McCarthy LG, Kosiol C, Healy AM, Bradley G, Sexton JC, Corrigan OI. Simulating the hydrodynamic conditions in the United States Pharmacopeia paddle dissolution apparatus. AAPS Pharm Sci Tech 2003 4(2) Article 22. McCarthy LG, Bradley G, Sexton JC, Corrigan OI, Healy AM. Computational fluid dynamics modeling of the paddle dissolution apparatus agitation rate, mixing patterns, and fluid velocities. AAPS Pharm Sci Tech 2004 5(2) Article 31. 

It is clear that under conditions of decomposition control the rate of dissolution of a solid in a liquid is independent of the thickness of the diffusion boundary layer and hence of the intensity of agitation of the liquid. By contrast, in the case of diffusion control the intensity of agitation of a liquid has a strong effect on the thickness of the diffusion boundary layer, thus influencing the value of the dissolution-rate constant, k. 

A number of experimental and theoretical studies of mass transfer in solution processes have been published. Since this literature is fairly well known, it will be mentioned briefly, but not analyzed in detail. Most of the earlier work in agitation employed dissolution rates as performance criteria (H6, H8, W5). Experimental studies of dissolution itself have employed suspended solute plates (B7, Wl), single crystals (M12, P5), revolving crystals (D2), and packed beds (Gl, L3, M5, V4). Recently, several theoretical analyses of literature data have appeared (El, HI, R3). A number of Russian investigators have also studied dissolution (N6, Zl) they prefer to correlate data in terms of individual variables rather than the dimensionless groups customary in English and American literature. 

The simple dissolution rate results were obtained using a laser interferometer with a 15 mw/cm He-Ne laser at normal incidence to the wafer surface in the agitated developer bath. The reflected beam was directed by a beam splitter onto a photocell. The photocell output was fed through a Keithly series 500 interface into an IBM-PC. The more complex dissolution data were collected on a Perkin-Elmer dissolution rate monitor using 934 developer at a 1 1 dilution with deionized water at a temperature of 21 C. The stepped exposures were obtained using a calibrated multidensity chrome stepwedge. 

Mackay and Wadsworth (M3) reported the dissolution kinetics of pure UO2 in sulfuric acid imder oxygen pressure of as high as 900 psi and 270°C. It was observed that the rate of dissolution follows a linear rate with time, that by proper agitation the reaction rate may be limited to a surface reaction alone, that the dissolution rate is directly proportional to the partial pressure of oxygen above the solution up to 900 psi, and that a single UO2 surface site adsorbs a water molecule to form 2 hydroxyls and act as a weak acid. 

Figure 4 Log (dissolution rate) versus pH for quartz at 25 °C measured in various pH buffers in agitated batch reactors. The slope of the log rate — pH curve equals 0.3 above the pristine point of zero charge (Brady and Walther, 1992) (source Brady and Walther, 1990).

Agitation usually enhances diffusion, reduces mass transfer limitation, and, therefore, increase dissolution rate. Vigorous agitation of solid is applied only to leaching of fine particles. 

The dissolution rate, rather than the saturation solubility, is most often the primary determinant in the absorption process of a sparingly soluble drug. Experimental determinations of the dissolution rate are therefore of great importance. The main area for dissolution rate studies is evaluation of different solid forms of a drug (e.g., salts, solvates, polymorphs, amorphous, stereoisomers) or effects of particle size. The dissolution rate can either be determined for a constant surface area of the drug in a rotating disc apparatus or as a dispersed powder in a beaker with agitation. 

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