Dissolution at porous interfaces V. Pore effects in a parallel-plate dissolution cell

Grijseels, H.; Blaey, C. J. De

doi:10.1016/0378-5173(83)90148-5

Cited by 5 publications

(3 citation statements)

References 8 publications

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“…However, the dissolution rate of crystalline indomethacin also decreases with time even though no solid phase change is observed. This phenomenon has been described previously and has been attributed to surface smoothing and disruption of fluid flow at the boundary surface due to surface roughness . Other groups have circumvented this anomaly by using the same drug compact for successive dissolution experiments .…”

Section: Resultsmentioning

confidence: 64%

Crystallization of Amorphous Indomethacin during Dissolution: Effect of Processing and Annealing

Greco

Bogner

2010

Mol. Pharmaceutics

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The crystallization of amorphous drugs during dissolution is a type of solution mediated phase transformation that can reduce the bioavailability enhancement one hoped to gain from the amorphous state. The goal of this study was to explore the effects of processing on the dissolution performance of amorphous indomethacin. The amorphous solids were prepared by four techniques, quench cooling the melted solid, cryogrinding γ indomethacin amorphous for 1 or 3 h and quench cooling the solid followed by 1 h of cryogrinding. Dissolution results assessed in a flow-through intrinsic dissolution apparatus reveal decreases in the dissolution rate of amorphous indomethacin during the experimental time frame indicating that a solution mediated phase transformation has occurred. The amorphous solids prepared by melt quenching and melt quenching followed by cryogrinding showed a significant dissolution rate advantage over the γ form of indomethacin. In contrast, indomethacin that was cryoground amorphous for 1 or 3 h did not show any dissolution rate advantage over the crystalline material. Transformation was confirmed by in situ Raman microscopy and polarized light microscopy with differences seen in the nature of the crystals apparent on the surface of the dissolving solid. A portion of the melt quenched amorphous sample was annealed at 25 °C and 0% relative humidity to induce partial crystallization of γ indomethacin. As crystallinity increased, the dissolution rate decreased. The transformation time of partially amorphous indomethacin was not dependent on the level of crystallinity present, indicating only a small fraction of crystalline material needs to be present to affect the kinetics of crystallization. The solution mediated phase transformation of amorphous indomethacin is affected by the processing method even though all solids were confirmed amorphous by polarized light microscopy and X-ray diffraction. Dissolution may distinguish differences in amorphous solids that other methods cannot discern.

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Section: Resultsmentioning

confidence: 64%

Crystallization of Amorphous Indomethacin during Dissolution: Effect of Processing and Annealing

Greco

Bogner

2010

Mol. Pharmaceutics

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“…Dabei werden die auf den Sieben verbleibenden Rückstandsmassen einzelnen Korngrößenklassen zugeordnet. "Rauhigkeiten" beeinflussen können (Levich 1962, § 29;Grijseels et al 1983). Die sich ausbildende Grenzschicht erleidet infolgedessen gravierende Veränderungen (Perry et al 1969).…”

Section: Materials Und Methodikunclassified

“…Das Konzept der hydrodynamischen Reibungsgrenzschicht findet seine einfachste Ausprägung am Beispiel der stationär angeströmten ebenen Platte. An diesem Modell wurden auch die meisten Messungen und Berechnungen zu Grenzschichtprofil und Grenzschichtaufbau ausgeführt (Blasius 1908, Perry et al 1969, Levich 1962, oder aber es wurde für die Deutung verschiedenster Experimente zugrundegelegt (Grijseels et al 1983, Opdyke 27 et al 1987 Re x,krit (Grenzschicht)~1160 (Millikan 1932;Bircumshaw et al 1952).…”

Section: Grenzschichtprofil An Der "Ebenen Platte"unclassified

Hydrodynamik und Lösungsgeschwindigkeit - Untersuchungen zum Einfluss der Hydrodynamik auf die Lösungsgeschwindigkeit schwer wasserlöslicher Arzneistoffe (rev. Fassung 2022) : Hydrodynamics and Dissolution - Influence of Hydrodynamics on Dissolution Rate of Poorly Soluble Drugs (rev. version 2022)

Diebold

2023

Preprint

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The objectives of the present study were to (1) examine both the hydrodynamics of compendial in vitro dissolution test apparatus as well as the respective in vivo gastrointestinal hydrodynamics in dogs, (2) describe the influence of hydrodynamics on the dissolution rates of poorly soluble drugs and (3) to develop a hydrodynamic based model to a priori predict dissolution rates of poorly soluble compounds. Hydrodynamics of compendial dissolution test apparatus (paddle and basket) were directly characterized by means of an ultrasound pulse echo method. Fluid velocities within the dissolution vessels correlated well and in a linear manner with the rotational speed (rpm) of both the paddle and basket test apparatus, respectively. Thus, based on this correlation, it was possible to calculate velocities of the dissolution media at any rotational speed. Fluid velocities were determined using the basket method to range between 0.3 and 5 cm/s (25 to 200 rpm) and for the paddle method to range between 1.8 and 37 cm/s. These fluid velocity data, determined empirically here for the first time in compendial dissolution vessels, are a prerequisite to forecast drug substance dissolution rates in vitro. In order to calculate such mass transfer rates the so called "Kombinations-Modell" was developed. This model is based on the convective diffusion theory by V.G. Levich. Here, we applied it on coarse and micronized felodipine powders as drug substance models as well as on oxygen as a model / vector to study hydrodynamics independent of chemical nature or state of aggregation. As a result, predicted dissolution rate data, calculated by means of the combination model, were found to correspond well with the respective dissolution rates determined by experiment. As expected, hydrodynamics did not discriminate between different states of aggregation of the two model compounds oxygen (gas) and felodipine (solid). Using the paddle method Reynolds numbers from Re=2292 to Re=31025 were calculated. In contrast, Reynolds numbers determined using the basket apparatus ranged from Re=231 to Re=4541. With respect to changes in hydrodynamic conditions particles of coarse grade felodipine were found to be more sensitive than micronized material of the same chemical species. A scintigraphic method was established to modulate intestinal hydrodynamics and to subsequently study gastric emptying and intestinal transit of caloric and non-caloric fluids in labradors. For orally administered solutions time needed for total gastric emptying (GE>95%) was found to depend on both volume and caloric content. GE>95% for 200 ml of 20 % aqueous glucose solution differed significantly (278 min.) from GE>95% for the same volume of 0.9 % sodium chloride solution (97 min.). After administration of 20 % glucose solution the mean duodeno-jejunal transit rate (MTR) was determined to be 2.7 cm/min. This was significantly different from measured MTR after administration of the same volume of 0.9 % sodium chloride solution (1.1 cm/min.). However, duodeno-jejunal transit itself was found not to correlate with gastric emptying. Gastro-intestinal flow rates (= flow influenced also by gastric emptying) were determined using an aspiration method. After administration of 200 ml of 20 % glucose solution gastro-intestinal flow rates reached (short time) maxima from 20 to 60 ml/min. (median: 8.3 ml/min.). In contrast, gastro-intestinal flow rates were found to be significantly higher following administration of 200 ml of 0.9 % sodium chloride solution, exhibiting (short lasting) maxima of up to 100 ml/min. (median: 35.0 ml/min.). Luminal dissolution rate of felodipine was found to be greater following coadministration of hypertonic (!) glucose than following coadministration of 0.9 % saline. This result correlated well with an increased intestinal fluid volume (collected 76 cm distal to the pylorus) following oral administration of 20 % glucose solution.

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