Dissolution Kinetics of Phenylbutazone

Mooney, K.G.; Rodriguez‐gaxiola, M.; Mintun, Mark A.; Himmelstein, Kenneth J.; Stella, V.J.

doi:10.1002/jps.2600701218

Cited by 32 publications

(27 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18,24 However, dissolution of Hf‚HCl cannot be completely accounted for by the convection-diffusion model as the intercepts of both plots were significantly greater than zero. Similar observations of a nonzero intercept have been reported for indomethacin 25 and phenylbutazone 26 where natural convection (which may occur at low rotational speeds) was suggested as an additional mechanism contributing to the dissolution process, although the basis for the non-zero intercept was not addressed. For indomethacin, 25 there was good agreement between the diffusivity calculated from the slope of the Levich plot and theoretical estimates, suggesting that any additional mechanisms contributing to dissolution were reflected in the intercept of the Levich plot, and not the slope.…”

Section: Intrinsic Dissolution Studiessthesupporting

confidence: 71%

A physicochemical Basis for the Effect of Food on the Absolute Oral Bioavailability of Halofantrine

Humberstone

Porter

Charman

1996

Journal of Pharmaceutical Sciences

122

134

View full text Add to dashboard Cite

Halofantrine hydrochloride (Hf.HCl) is a highly lipophilic phenanthrenemethanol antimalarial. The poor and erratic absorption of Hf after oral administration has been implicated in some treatment failures. Food increases the oral bioavailability of Hf in humans approximately 3-5-fold, although neither the absolute bioavailability nor the basis for the food effect has been fully defined. In this study, the mean (+/-SD, n = 3) absolute oral bioavailability of 250 mg Hf.HCl tablets in beagles was 8.6 +/- 5.3% in the fasted state, which increased approximately 12-fold when administered postprandially. These data indicate that Hf.HCl is efficiently absorbed from the postprandial intestinal environment. The solubility and intrinsic dissolution rate of Hf.HCl were investigated as a function of bile salt concentration (sodium taurocholate, NaTC, 0-30 mM) and micellar composition (4:1 NaTC:lecithin). At premicellar (fasted) concentrations of NaTC (< 5 mM), the solubility and intrinsic dissolution rate were very low (< 15 micrograms/mL; < 0.01 microgram s-1 cm-2). At NaTC concentrations typical of the postprandial state, the solubility and dissolution rate improved dramatically. For example, solubility in 30 mM NaTC increased approximately 1000-fold relative to buffer control, with even greater enhancement (3000-fold) associated with mixed micellar systems. These data suggest that the improved absorption of Hf.HCl in the fed state is most likely due to the increased solubilization and dissolution of the drug in the presence of bile salt mixed micelles.

show abstract

Section: Intrinsic Dissolution Studiessthesupporting

confidence: 71%

A physicochemical Basis for the Effect of Food on the Absolute Oral Bioavailability of Halofantrine

Humberstone

Porter

Charman

1996

Journal of Pharmaceutical Sciences

122

134

View full text Add to dashboard Cite

show abstract

“…However, as has been shown by Mooney et nl. (19) this is generally not the case and may give erroneous results. The use of the extension of the Higuchi model for dissolution behavior in buffer solutions, as has been proposed by Mooney et af.…”

Section: Resultsmentioning

confidence: 90%

“…The use of the extension of the Higuchi model for dissolution behavior in buffer solutions, as has been proposed by Mooney et af. (19) may, however, form a suitable basis for the determination of pK, values in such media.…”

Section: Resultsmentioning

confidence: 97%

Determination of the Dissociation Constant of a Weak Acid Using a Dissolution Rate Method

Hansen

Häfliger

1983

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

“…In the case of a dissociable compound, S surface is different from S dissolv due to the self-buffering effect of dissolving drugs [2] [25]. V GI is the volume of the GI fluid.…”

Section: Overview Of Computational Oral Absorptionmentioning

confidence: 99%

Computational Oral Absorption Simulation for Low‐Solubility Compounds

Sugano

2009

Chemistry & Biodiversity

View full text Add to dashboard Cite

Bile micelles play an important role in oral absorption of low-solubility compounds. Bile micelles can affect solubility, dissolution rate, and permeability. For the pH-solubility profile in bile micelles, the Henderson-Hasselbalch equation should be modified to take bile-micelle partition into account. For the dissolution rate, in the Nernst-Brunner equation, the effective diffusion coefficient in bile-micelle media should be used instead of the monomer diffusion coefficient. The diffusion coefficient of bile micelles is 8- to 18-fold smaller than that of monomer molecules. For permeability, the effective diffusion coefficient in the unstirred water layer adjacent to the epithelial membrane, and the free fraction at the epithelial membrane surface should be taken into account. The importance of these aspects is demonstrated here using several in vivo and clinical oral-absorption data of low-solubility model compounds. Using the theoretical equations, the food effect on oral absorption is further discussed.

show abstract

Dissolution Kinetics of Phenylbutazone

Cited by 32 publications

References 8 publications

A physicochemical Basis for the Effect of Food on the Absolute Oral Bioavailability of Halofantrine

A physicochemical Basis for the Effect of Food on the Absolute Oral Bioavailability of Halofantrine

Determination of the Dissociation Constant of a Weak Acid Using a Dissolution Rate Method

Computational Oral Absorption Simulation for Low‐Solubility Compounds

Contact Info

Product

Resources

About