Dissolution Rate Constants Research Articles

Understanding agglomeration of indomethacin during the dissolution of micronised indomethacin mixtures through dissolution and de-agglomeration modeling approaches

The purpose of this research was to correlate the state of agglomeration determined by the modeling of dissolution and de-agglomeration profiles, using mixtures of micronised indomethacin designed to have different dissolution rates and extents of particle agglomeration in dissolution media. Dissolution profiles were determined using the USP paddle method. De-agglomeration profiles were obtained from laser diffraction particle sizing of mixtures of indomethacin in dissolution media under non-sink conditions. Data were modeled and key parameters estimated using a non-linear least squares estimation algorithm. The key parameters of initial apparent volume concentrations as dispersed and agglomerated particles, and dissolution rate constants (for dissolution modeling), and the apparent volume concentrations of dispersible and non-dispersible agglomerates and the de-agglomeration rate constant (for de-agglomeration modeling) were related to indomethacin and sodium lauryl sulphate concentrations in the lactose–povidone mixtures. Micronised sodium lauryl sulphate added to the mixture was more effective in de-agglomeration than equivalent concentrations in the dissolution media. An excellent correlation existed between the total initial apparent volume concentration of agglomerates determined by dissolution and de-agglomeration ( P=0.98). The use of key parameters estimated from the modeling of dissolution and de-agglomeration profiles provides a useful tool in dosage form development of formulations of poorly water soluble drugs.

Leaching of borosilicate glasses. II. Model and Monte-Carlo simulations

A model for the corrosion of sodium borosilicate glasses is developed. Numerical simulations based on this model are worked out and compared with the results of the experimental companion paper. The glass structure is represented by a diamond lattice on the vertices of which the silicon and boron atoms are randomly distributed. The sodium cations are put in interstitial position and cause lattice depolymerization. Sodium and boron are assumed to be immediately dissolved when they stand at the solid–solution interface. The reaction of glass with water is described by three dissolution rate constants corresponding to silicon with one, two or three siloxane bonds. Dissolved silicon atoms (but not boron neither sodium) are allowed to condense again on the surface. The simulations show that the silicon concentration in solution saturates to a value which is controlled by the ratio of the dissolution to condensation rate constants. The silicon dissolution–condensation dynamics leads to a restructuring of the surface altered layer, which, in most cases, causes a corrosion blocking and limits the release of boron and sodium in solution. Since boron and sodium are thoroughly removed from the surface altered layer, the corrosion can be characterized by the final equivalent leached thickness in boron or sodium. The variation of this quantity is studied as a function of the glass composition and of the model parameters. This study put in evidence two regimes of corrosion, which are controlled by silica dissolution at low boron oxide content, and by boron leaching at high boron oxide content. With an appropriate choice of the silicon reactivity parameters, it is possible to reproduce quantitatively the variation of the equivalent leached thicknesses with the glass composition in two series of experiments at two different S/ V ratios ( S/ V is the ratio of the initial glass surface area exposed to leaching to the volume of the solution). The corrosion blocking is explained in terms of percolation.

Kinetics of Gold Dissolution in Thiosemicarbazide Solutions

The kinetics of gold dissolution in thiosemicarbazide solutions was studied relative to the ratio of ferric ion and thiosemicarbazide concentrations as well as pH. The composition of the complex formed was found to be [Au(NH2)2NHC=S3]+. The rate constants for gold dissolution were determined at 278-298 K along with the stability, dissociation, and equilibrium constants at 288 K. The activation energy at 288 K was also found.

Analytical derivation of time required for dissolution of monodisperse drug particles

whereM is the mass of solid material at time t, k is the dissolution rate constant, A is the area available for mass transfer, D is the diffusion coefficient of the dissolving material, and h is the diffusion boundary layer thickness. Dosage forms rarely contain solid drug-containing particles that maintain constant surface area for mass transfer however, and the following considerations are required to model dissolution of monodisperse powders:

Numerical simulation of controlled nifedipine release from chitosan microgels

AbstractThe numerical simulating investigation of drug delivery can provide deeper insight into drug release mechanisms and elucidate efficiently the influences of various physical parameters. Controlled nifedipine release from nonswellable chitosan sphere‐based microgels is investigated numerically with a mathematical model in this article. The mathematical model takes into account both drug dissolution and drug diffusion through the continuous matrices of the spherical microgels. Meshless Hermite‐cloud method is employed to solve the formulated partial differential equations. It is seen that the model well describes the nifedipine release process from the spherical chitosan microgels. The effect of several important physical parameters on drug release is evaluated, which include microsphere radius, equivalent drug saturation concentration, drug diffusion coefficient, and drug dissolution rate constant. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1928–1937, 2004

Solubility of airborne radioactive fuel particles from the Chernobyl reactor and implication to dose.

Airborne particles of nuclear fuel from the Chernobyl reactor that had been collected on air filters and stored, were characterised using in vitro dissolution tests to assess effective doses after their inhalation. As solvent, the Gamble biological fluid was used to simulate lung fluid. The solubility of the measured radionuclides decreased in the order (137)Cs>(90)Sr>>(241)Am>or=(239+240)Pu in the simulated lung fluid. The dissolution rate constant of e.g. (239+249)Pu ranged from 0.72 to 5.4 x 10(-6) g x cm(-2) d(-1) and decreased (for all nuclides) with increasing particle size as predicted from theoretical considerations. Considering the inhalation dose, decreasing dose with size and increasing doses with lower solubility may partly counterbalance each other for (137)Cs and (90)Sr. On the other hand, for (239)Pu and (241)Am larger particles and associated lower solubility both change the resulting dose in the same direction towards lower values. The comparison of the experimentally determined dose coefficients with ICRP values indicates that nuclear fuel particles closely resemble type M material characteristics for (137)Cs and (90)Sr and type S material characteristics for (239)Pu and (241)Am.

Modelling the interaction of hyperalkaline fluids with simplified rock mineral assemblages

Designs for geological disposal facilities for radioactive wastes often envisage the extensive use of cementitious materials. After closure, the repository will saturate with groundwater and cement porewater will migrate into the geosphere to form an alkaline (pH 12.5–13) plume. This plume will react with the components of the surrounding host rock leading to mineralogical, chemical and physical changes which will be complex in nature. Coupled computer models of geochemistry and hydrogeological transport will be needed to scope these changes. In the recent past, a series of laboratory column experiments were carried out by the British Geological Survey in order to test the capabilities of coupled models to predict the evolution of outflow fluid compositions and product solids. These experiments reacted single minerals (i.e., quartz, albite, calcite and muscovite/quartz) and potential host rock lithologies (i.e., Borrowdale Volcanic Group fault rock, Äspö granite and Wellenberg marl) with cement pore fluids. The objectives of the present work were to develop the understanding of these experiments and to improve simulations of the data by computer models. To this end, a systematic approach was adopted in which dissolution rates for individual minerals were calibrated to the results of the single mineral columns and the resulting parameter values applied to the more complex columns. It was found that for the systems studied, reasonable agreement between the experimental data and the calculated results could be obtained. However, the calibrated dissolution rate constants used in the models first vary between experiments by up to half an order of magnitude and secondly differ from literature values by up to one order of magnitude, with the calibrated values being generally slower than those found in the literature.

A novel channel flow method in determination of solubility properties and dissolution profiles of theophylline tablets

A recently developed channel flow dissolution method was applied in the determination of compound solubility and the dissolution profiles of theophylline tablet formulations. As reference methods were used the USP basket and intrinsic dissolution methods. The four tablet compositions studied contained various proportions of lactose, microcrystalline cellulose (MCC), talc and magnesium stearate as pharmaceutical ingredients. The equilibrium constants of the dissolution reaction of theophylline (describing the relation between the dissolution and precipitation rate constants) in the individual tablet formulations, determined by the channel flow method, were similar at pH values of 1.2 and 6.8. The intrinsic dissolution rate of theophylline was slightly increased (from 0.9 to 1.1mg/(cm2min)) as the pH of the medium was decreased. There were clear differences between the results of channel flow and USP basket methods. In the channel flow apparatus the two formulations including the highest amounts of MCC liberated the drug substance the slowest, while with the USP basket method the compositions including either MCC alone or the highest amount of lactose liberated the drug substance the slowest. These release profiles were caused by the different disintegration behaviour of the tablets in the two methods. The advantages of the channel flow method include the analysis of solubility properties of the drug substance and, in particular, when compared to the USP basket method, the study of the early stages of the dissolution process.

Gypsum solubility in seawater, and its application to bauxite residue amelioration

The solubilities and dissolution rates of 3 gypsum sources [analytical grade reagent (AR), phosphogypsum (PG), mined gypsum (MG)] with 6 MG size fractions (>2.0, 1.0–2.0, 0.5–1.0, 0.25–0.5, 0.125–0.25, <0.125 mm) were investigated in triple-deionised water (TDI) and seawater to examine their suitability for bauxite residue amelioration. Gypsum solubility was greater in seawater (3.8 g/L) than TDI (2.9 g/L) due to the ionic strength effect, with dissolution in both TDI and seawater following first-order kinetics. Dissolution rate constants varied with gypsum source (AR > PG > MG) due to reactivity and surface area differences, with 1 : 20 gypsum : solution suspensions reaching saturation within 15 s (AR) to 30 min (MG >2.0 mm). The ability of bauxite residue to adsorb Ca from solution was also examined. The quantity of the total solution Ca adsorbed was found to be small (5%). These low rates of solution Ca adsorption, combined with the comparatively rapid dissolution rates, preclude the application of gypsum to the residue sand/seawater slurry as a method for residue amelioration. Instead, direct field application to the residue would ensure more efficient gypsum use. In addition, the formation of a sparingly soluble CaCO3 coating around the gypsum particles after mixing in a highly alkaline seawater/supernatant liquor solution greatly reduced the rate of gypsum dissolution.

Experimental study of brucite dissolution and precipitation in aqueous solutions: surface speciation and chemical affinity control

Dissolution and precipitation rates of brucite (Mg(OH) 2) were measured at 25°C in a mixed-flow reactor as a function of pH (2.5 to 12), ionic strength (10 −4 to 3 M), saturation index (−12 < log Ω < 0.4) and aqueous magnesium concentrations (10 −6 to 5·10 −4 M). Brucite surface charge and isoelectric point (pH IEP) were determined by surface titrations in a limited residence time reactor and electrophoretic measurements, respectively. The pH of zero charge and pH IEP were close to 11. A two-pK, one site surface speciation model which assumes a constant capacitance of the electric double layer (5 F/m 2) and lack of dependence on ionic strength predicts the dominance of >MgOH 2 + species at pH < 8 and their progressive replacement by >MgOH° and >MgO − as pH increases to 10–12. Rates are proportional to the square of >MgOH 2 + surface concentration at pH from 2.5 to 12. In accord with surface speciation predictions, dissolution rates do not depend on ionic strength at pH 6.5 to 11. Brucite dissolution and precipitation rates at close to equilibrium conditions obeyed TST-derived rate laws. At constant saturation indices, brucite precipitation rates were proportional to the square of >MgOH 2 + concentration. The following rate equation, consistent with transition state theory, describes brucite dissolution and precipitation kinetics over a wide range of solution composition and chemical affinity: R=k Mg + · {>MgOH 2 +} 2 · (1−Ω 2) where k Mg + is the dissolution rate constant, {> i} is surface species concentration (mol/m 2), and Ω is the solution saturation index with respect to brucite. Measurements of nonsteady state brucite dissolution rates, in response to cycling the pH from 12 to 2 (pH-jump experiments), indicate the important role of surface hydroxylation — that leads to the formation of Mg oxo or –hydroxo complexes — in the formation of dissolution-active sites. Replacement of water molecules by these oxygen donor complexes in the Mg coordination sphere has a labilizing effect on the dynamics of the remaining water molecules and thus increases reaction rates.

Respiration, dissolution, and the lysocline

Here I synthesize the results of several types of measurements of organic carbon respiration and calcium carbonate dissolution rates in pelagic seafloor sediments. Measurements of pore water oxygen demonstrate that most of the respiration takes place very near the sediment‐water interface, with a scale depth of a few millimeters. The remainder of the oxic respiration occurs much deeper in the sediments, with a scale depth of several centimeters. All measures of respiration from locations as disparate as the tropical Pacific and Atlantic, and the subtropical North Atlantic agree that pelagic seafloor rates of oxic respiration of organic carbon are relatively independent of depth and location, with the exception of sediments beneath the Pacific eastern equatorial upwelling zone. Calcite dissolution in seafloor sediments requires forcing by respiration‐produced CO2, and rates are consistent with a first‐order dependence on pore water undersaturation, solubility as determined by Mucci [1983] at atmospheric pressure, and locally variable mass‐specific dissolution rate constants. Respiration‐driven calcite dissolution fluxes predicted by this combination of respiration and dissolution rate expressions are significantly lower than many previous estimates. Comparison of dissolution fluxes in the oligotrophic open ocean measured by other researchers with benthic chamber incubation techniques with those predicted by this combination of rate expressions is, within stated uncertainties, in agreement in all but one case, questioning the need for complicated mechanisms such as surface buffering or authigenic precipitation to explain seafloor calcite diagenesis. Applying these kinetics to a simple one‐dimensional, steady state model of the bulk calcite content and sediment accumulation rates of the sediment mixed layer yields results consistent with observations of the seafloor lysocline, the region of transition from high calcite to low‐calcite sediments, on the Ceara Rise in the western tropical North Atlantic and the Ontong‐Java Plateau in the western equatorial Pacific. Scenarios ignoring dissolution driven by respiration‐produced CO2 in pore waters and using the high‐order dependence on undersaturation and very large dissolution rate constants implied by some earlier laboratory studies do not simulate these observations. While the scheme represented here does, in fact, imply a strong shift in the locus of carbonate dissolution toward the sediment water interface as bottom‐water saturation decreases, as implied by the observations of Martin et al. [2000], no simple combination of sediment transport coefficients and reaction kinetics can reproduce the observation of increasing 14C age as dissolution progresses. These results emphasize the importance of accurate knowledge of the kinetics of respiration and dissolution to interpretation of either the present‐day or paleolysocline.

Electrochemical dissolution of simulated "white inclusions". Kinetics and material balance for Mo, Re, Ru metals and their alloys during electrochemical dissolution in nitric acid

Abstract The kinetics of pure Mo, Re and Ru metals, as well as their alloys 52.5at. Mo – 47.5at. Re and 90at. Mo – 10at. Ru electrochemical dissolution during potential controlled electrolysis at a temperature T=25 °C in 0.5–6.0M HNO3 solutions were studied. The dissolution kinetics for all metal and alloy electrodes under study were found to be of zero order vs. metal concentration in the electrolyte. Rate constants for Mo electrochemical dissolution increased from 1.68×10-3 to 5.99×10-3mol cm-2h-1 with the growth of HNO3 concentration in the electrolyte from 0.5 to 4.0M. Further increase of the acid concentration in the solution to 6.0M did not result in the acceleration of Mo electrochemical dissolution. Rate constants of Re and Ru metals electrochemical dissolution increased monotonously from 4.27×10-4 to 1.7×10-3mol cm-2 h-1 for Re and from 1.28×10-4 to 1.61×10-3mol cm-2 h-1 for Ru with the rise of HNO3 concentration from 0.5 to 6.0M. Dissolution of Mo-Re and Mo-Ru alloys was congruent. With the increase of HNO3 concentration in the electrolyte from 0.5 to 6.0M, the dissolution rate constant of Mo-Re alloy was increasing from 1.33 to 7.60×10-3mol(Mo+Re)cm-2h-1. Maximum rates of Mo-Ru alloy electrochemical dissolution from 2.21×10-3 to 3.28×10-3mol(Mo+Ru)cm-2 h-1 were observed in 2.0–4.0M HNO3 at the electrolysis potential E=1.6V/SCE. The main electrochemical and chemical processes occurring at the metal and alloy electrodes and resulting in the metals dissolution are pointed out.

Predicting benthic fluxes of silicic acid from deep‐sea sediments

Benthic fluxes of silicic acid are driven by the dissolution of biogenic opal deposited at the seafloor. The fluxes vary over several orders of magnitude and correlate inversely with the mass ratio of lithogenic matter to biogenic opal of the sediments. The role of the lithogenic, or detrital, sediment fraction was studied in batch reactors, by monitoring the release of silicic acid from mixtures of a well‐characterized biosiliceous ooze from the Southern Ocean and model lithogenic materials (kaolinite or basalt). The rate constant of silicic acid production and the saturation silicic acid concentration decreased systematically with increasing detrital to opal mass ratio of the mixtures. Both effects, which are attributed to the release of soluble aluminum from lithogenic mineral phases, were incorporated into an early diagenetic model to calculate diffusive benthic silicic acid fluxes from deep‐sea sediments. The apparent silica dissolution rate constant, the saturation (or asymptotic) pore water silicic acid concentration, and the concentration of biogenic opal were the critical parameters determining the model‐derived benthic fluxes. Predicted benthic fluxes of silicic acid were compared to values reported for deep‐sea sediments with known detrital to opal ratio and asymptotic pore water concentration. When taking into account the dependence of pore water silicic acid build up on the detrital sediment fraction, good agreement was found between predicted and measured benthic fluxes, over a wide range of oceanic areas and sediment composition, from opal rich to opal poor sediments. The model provides a means to estimate the benthic flux of silicic acid for deep‐sea sediments for which the asymptotic silicic acid concentration and the composition of the uppermost sediment are known.

Analysis of pore‐scale nonaqueous phase liquid dissolution in etched silicon pore networks

Predicting the dissolution rate of nonaqueous phase liquids (NAPLs) in groundwater is difficult, as the effects of variable pore and NAPL blob geometry are poorly understood. To elucidate these effects, fluorescence microscopy and digital image analysis were used to quantify the size and location of variably distributed NAPL blobs during dissolution in homogeneous and heterogeneous pore networks etched into silicon wafers. Results show that the dissolution rate constant (expressed as the Sherwood number, Sh) is relatively constant regardless of pore and NAPL blob geometry when the average mass transfer length scale remains constant during dissolution. Results also show that Sh increases with Peclet (Pe) between 2 and 26 and then levels off. The limiting value of Sh reached depends on the average diffusion length scale; this length scale was directly calculated and found to vary depending on the pore and NAPL blob geometry. For example, the average diffusion length scale decreases (and Sh increases) as the pore throat width to grain diameter increases. Last, results show that the volumetric NAPL content (θn) is linearly related to the specific NAPL‐water interfacial area (ait) over much of the dissolution process. However, this relationship depends on the pore and blob size distribution. For example, when multipore blobs control dissolution, the relationship between these parameters will change as smaller blobs dominate dissolution at low θn. These results are important because existing mass transfer correlations do not account for limiting values of Sh that can be obtained at high Pe for the effect of blob or pore geometry on the average diffusion length scale (and therefore on Sh) or for the effect of pore geometry and transient blob size distribution on the relationship between ait and θn.

Electrochemical dissolution of simulated "white inclusions" in nitric acid. Linear voltammetry study with Mo, Re, Ru metals and their alloys electrodes

Summary The process of electrochemical dissolution of pure Mo, Re and Ru metals, as well as their alloys 52.5 at. Mo – 47.5 at. Re and 90 at. Mo – 10 at. Ru in 0.5-6.0M HNO3 was studied using the linear voltammetry technique. The dissolution potentials of the pure metals were found to increase from 0.39 to 0.48V/SCE (Mo), from 0.7 to 0.81V/SCE (Re) and from 1.15 to 1.25V/SCE (Ru) with the augmentation of HNO3 concentration in the electrolyte. The dissolution potentials of the alloys 52.5 at. Mo + 47.5 at. Re and 90 at. Mo + 10 at. Ru were found to change from 0.49 to 0.58 (Mo-Re) and from 0.92 to 1.09 (Mo-Ru) when HNO3 concentration in the electrolyte increased from 0.5 to 6.0M. The secondary passivation of Mo-containing electrodes was observed in the solutions 2.0-6.0M HNO3 at the potentials from 1.4 to 1.9V/SCE, decreasing their dissolution rate in this range of potentials. The maximum electrochemical dissolution rate constants of pure Mo, Re, Ru metals and Mo-Re, Mo-Ru alloys have been estimated using the data of linear voltammetry. The obtained values (1.85-2.20g/cm2 h for Mo-Re and 0.58-0.64g/cm2 h for Mo-Ru alloys electrochemical dissolution) are found to be thousand times greater, than reported for the process of chemical dissolution of corresponding alloys in boiling HNO3.

Dissolution of model coal minerals (gypsum and pyrite) in RuCl3 solution—a demineralisation approach

Abstract Gypsum accounts for sulfate sulfur and pyrite for pyritic sulfur, are occurring in coal; dissolution of their model samples were carried out using RuCl 3 solution. The extent of soluble calcium from gypsum at 25 °C was 97.67–98.26% in 15–60 min while the extent of soluble iron from pyrite was 0.35–0.65% at 25 °C and 3.90–6.31% at 80 °C in the same time period. The rate constants for gypsum dissolution are exceedingly higher (1.12–4.23)10 −3 s −1 , than those observed for pyrite, (1.58–3.92)10 −6 s −1 . It is observed that RuCl 3 is a suitable reagent for the removal of gypsum by dissolution process.

Surface alteration of dolomite in dedolomitization reaction in alkaline media

The phases precipitated on the dolomite surface and the influence of alkalis on the properties of this surface were characterized. Experiments consisted of the immersion of single crystals of dolomite in saturated portlandite solutions with different alkalinity, temperature, and silica content. Most calcite forms in the solution as {104} rhombohedra. Brucite crystallizes as platelets, piles of platelets, sponge-like and {001} truncated ditrigonal pyramids attached to the dolomite surface. The morphology of brucite crystals depends on the pH of the solution. Apparent dissolution rate constants for dolomite at 75 °C are one order of magnitude higher than at room temperature. Initially, calcite grows on the dolomite surface with the same structural orientation {104}. In a second stage, when calcite has reached equilibrium with the solution, the new-formed {104} calcite surface starts playing an important role on the precipitation of brucite, while calcite continues crystallizing in the bulk solution. The calcite surface, negatively charged, can adsorb specifically metal cations. Mg 2+, liberated by the dissolution of dolomite, would move attached to the surface, until they are trapped on these negatively charged surfaces, while OH − supplied by the alkaline solution favors the nucleation and growth of brucite. The attachment of Mg 2+ to the surface controls the place where brucite grows.

Effect of surface modification on hydration kinetics of carbamazepine anhydrate using isothermal microcalorimetry.

The purpose of this research was to improve the stability of carbamazepine (CBZ) bulk powder under high humidity by surface modification. The surface-modified anhydrates of CBZ were obtained in a specially designed surface modification apparatus at 60 degrees C via the adsorption of n-butanol, and powder x-ray diffraction, Fourier-Transformed Infrared spectra, and differential scanning calorimetry were used to determine the crystalline characteristics of the samples. The hydration process of intact and surface-modified CBZ anhydrate at 97% relative humidity (RH) and 40 +/-C 1 degrees C was automatically monitored by using isothermal microcalorimetry (IMC). The dissolution test for surface-modified samples (20 mg) was performed in 900 mL of distilled water at 37 +/-C 0.5 degrees C with stirring by a paddle at 100 rpm as in the Japanese Pharmacopoeia XIII. The heat flow profiles of hydration of intact and surface-modified CBZ anhydrates at 97% RH by using IMC profiles showed a maximum peak at around 10 hours and 45 hours after 0 and 10 hours of induction, respectively. The result indicated that hydration of CBZ anhydrate was completely inhibited at the initial stage by surface modification of n-butanol and thereafter transformed into dihydrate. The hydration of surface-modified samples followed a 2-dimensional phase boundary process with an induction period (IP). The IP of intact and surface-modified samples decreased with increase of the reaction temperature, and the hydration rate constant (k) increased with increase of the temperature. The crystal growth rate constants of nuclei of the intact sample were significantly larger than the surface-modified sample's at each temperature. The activation energy (E) of nuclei formation and crystal growth process for hydration of surface-modified CBZ anhydrate were evaluated to be 20.1 and 32.5 kJ/mol, respectively, from Arrhenius plots, but the Es of intact anhydrate were 56.3 and 26.8 kJ/mol, respectively. The dissolution profiles showed that the surface-modified sample dissolved faster than the intact sample at the initial stage. The dissolution kinetics were analyzed based on the Hixon-Crowell equation, and the dissolution rate constants for intact and surface-modified anhydrates were found to be 0.0102 +/-C 0.008 mg(1/3) x min(-1) and 0.1442 +/-C 0.0482 mg(1/3) x min(-1). The surface-modified anhydrate powders were more stable than the nonmodified samples under high humidity and showed resistance against moisture. However, surface modification induced rapid dissolution in water compared to the control.

The mean dissolution time depends on the dose/solubility ratio.

To investigate the relationship between mean dissolution time (MDT) and dose/solubility ratio (q) using the diffusion layer model. Using the classic Noyes-Whitney equation and considering a finite dose, we derived an expression for MDT as a function of q under various conditions. q was expressed as a dimensionless quantity by taking into account the volume of the dissolution medium. Our results were applied to in vitro and in vivo data taken from literature. We found that MDT depends on q when q < 1 and is infinite when q > 1 and that the classic expression of MDT = 1/k. where k is the dissolution rate constant, holds only in the special case of q = 1. For the case of perfect sink conditions, MDT was found to be proportional to dose. Using dissolution data from literature with q < 1, we found better estimates of MDT when dependency on dose/ solubility ratio was considered than with the classic approach. Prediction of dissolution limited absorption was achieved for some of the in vivo drug examples examined. The mean dissolution time of a drug depends on dose/ solubility ratio, even when the model considered is the simplest possible. This fact plays an important role in drug absorption when absorption is dissolution limited.

Physicochemical Characterization and Drug Release Studies of Nilvadipine Solid Dispersions Using Water-Insoluble Polymer as a Carrier

Nilvadipine solid dispersions were prepared by the solvent method using water-insoluble polymers, including low-substituted hydroxypropylcellulose, croscarmellose sodium, carmellose calcium, carmellose, and crospovidone. Differential scanning calorimetry and powder x-ray diffraction analysis showed that nilvadipine was present in an amorphous state in the solid dispersion obtained using crospovidone as a carrier. The degree of crystallinity of nilvadipine was dependent on the ratio of nilvadipine to crospovidone, and nilvadipine was present in an amorphous state when the ratio of nilvadipine to crospovidone was below one-half. Fourier transform infrared studies suggested the presence of hydrogen bonding between nilvadipine and crospovidone in the solid dispersion. Dissolution studies indicated that the maximum percentage of dissolution and dissolution rate constants were markedly increased in nilvadipine with crospovidone solid dispersion, compared with those of pure nilvadipine and physical mixtures. The dissolution rate of nilvadipine solid dispersion with crospovidone could be calculated by the Higuchi square root time equation.