Determination Of Dissolution Rate Research Articles

An investigation of the disintegration of tablets in biorelevant media

The purpose of the study was to examine the disintegration of tablets in media designed to simulate conditions pertaining in the stomach. Although many studies have been performed to determine dissolution rates in these media, little work has been undertaken on the preliminary step in dissolution, namely disintegration. Two tablet formulations were prepared. One disintegrated rapidly (under 25 s in water) and the other more slowly (8 min in water). The disintegration times were measured by the BP 2000 test using discs. For the rapidly disintegrating tablets, disintegration times were similar in all media except for whole milk. This media is used to simulate the fed stomach and disintegration times were over five times longer than in the other media ( P < 0.05). A similar effect was seen with the poorly disintegrating tablets in milk, and prolonged times were also observed in some of the other media. For these latter media, there was a good correlation between the penetration rate of the fluid into the tablet and the disintegration time. Penetration rates for milk were also slow which may be a reflection of its relatively high viscosity and low surface tension.

Measurement of Acid Reaction Rates of a Deep Dolomitic Gas Reservoir

Abstract A rotating disk instrument was used to measure acid reaction rates, reaction order, and activation energy of reservoir rock from a deep dolomitic gas reservoir in Saudi Arabia. These values are required to optimize acidizing simulations. Results of more than 50 experiments are reported in this paper. Measurements were made from room temperature to 85 ° C at rotational speeds of 100 to 1,000 r/min and acid concentrations of 0.05 to 5 M HCl (0.2 to 17 wt%). The results show how acid dissolution rates change as the reservoir rock varied from 3 to 100 wt% dolomite. Factors affecting the measured parameters are discussed in detail. It was found that the reactivity of the rock varied from values expected for pure calcite marble to those expected for pure dolomite marble. At grain densities near 2.72 kg/dm3 (expected for pure calcite), rock dissolution rates varied by more than an order of magnitude, due to rock mineralogy. At grain densities near 2.83 kg/dm3 (expected for pure dolomite), rock dissolution rates were igher than that observed with pure dolomitic marble. Reaction rates depended on mineralogy and the presence of trace components such as clays. Introduction An accurate knowledge of acid reaction rates of deep gas reservoirs can contribute to the success of matrix and acid fracture treatments. These parameters are used in simulation models to estimate the optimum acid concentration, pumping rate, and shut-in time of acid treatments. Many studies of acid stimulation treatments of formation K, a deep, dolomitic gas reservoir in Saudi Arabia, have been published(1–3). This is the first study of acid reaction rates and reaction coefficients of this important formation. The rotating disk instrument is widely used in the petroleum industry for kinetic studies of the reaction of acidic fluids and chelating agents with reactive rock(4–10). This system allows the determination of rock dissolution rate, reaction rate constants, reaction order, and diffusion coefficients(4,11). In the rotating disk instrument, a rock disk 3.81 cm (1.5 in.) in diameter is mounted on a spindle using heat-shrink Teflon ® tubing. The rock disk can be spun at rates up to 1,000 r/min in a Hastelloy? B2 reaction vessel. Acid solution is preheated in a Hastelloy? B2 acid reservoir and transferred under pressure into the reaction vessel(4). Small volumes (8 mL) are removed from the reaction vessel every 2 minutes for 20 minutes. Concentrations of calcium and magnesium in the samples are determined by inductively coupled argon plasma emission spectroscopy. From the calcium and magnesium concentrations, and accounting for the loss of acid volume from the reactor, the amount of acid that reacted with the rock can be calculated for each sample(8). A plot of calculated acid concentrationvs. time shows the rate of acid consumption with time. From the slope of this line, and the surface area of the rock disk, the dissolution rate (moles/s cm2) can be calculated(6, 8). Test pressure was set at 6.9 MPa so that carbon dioxide would remain in solution.

Direct Visualization of Calcium Oxalate Monohydrate Crystallization and Dissolution with Atomic Force Microscopy and the Role of Polymeric Additives

The growth and dissolution of calcium oxalate monohydrate (COM) were investigated by real-time in situ atomic force microscopy (AFM). The (100) surfaces of COM crystals were sufficiently rough that direct AFM imaging of terrace growth and step motion was not feasible. In undersaturated aqueous solutions, however, COM crystals dissolved, developing elongated hexagonal pits oriented along the [001] direction and having perimeters defined by {010} and {021} planes, which mimics the habit of the macroscopic crystals. Increasing the concentration of calcium oxalate to supersaturated levels reversed etching, resulting in gradual filling of the pits, which is tantamount to crystal growth. The confinement of growth within the pits permitted observation of crystal growth events, in real time and at the microscopic level, which could not be deduced by inspection of the rough surfaces of the COM crystals. This approach allowed determination of growth and dissolution rates along specific crystallographic directions, ...

Determination of Oxygen Dissolution Rate from Silica to Silicon Melt at Solid (Silica Glass)/Melt/Gas Triple Junction

In growth of single crystal silicon by the Czochralski technique, it is important to know the actual value of the oxygen dissolution rate from silica glass to silicon melt at the triple-junction point of solid (silica glass)/liquid (silicon melt)/gas (argon). For the purpose of determining this value, a numerical simulation model was developed for the sessile drop experiment. In order to satisfy the presence of oxygen concentration along the melt/gas interface, a new interface condition was introduced in the model. Numerical simulation results are in good agreement with experiments. The values of oxygen dissolution rate at the condition corresponding to the triple-junction point (a very small drop that is not possible to form experimentally) were computed. The computed value at this point is about two times larger than the experimentally measurable value by the sessile drop method. © 2002 The Electrochemical Society. All rights reserved.

Electrochemical determination of dissolution rates of lyophilized pharmaceutical formulations.

We present a method to measure dissolution times for rapidly dissolving lyophilized formulations. K4Fe(CN)6 was lyophilized in formulations containing sucrose, salts, and Tween 20. Dissolution of the lyophilized powders was measured by monitoring the time dependence of the oxidation of Fe(CN)6(4-) ion at the surface of a platinum rotating disk electrode. Reconstitution of lyophilized K4Fe(CN)6 formulations with aqueous solutions of 0.03% Tween 20 altered the time of dissolution for all cases. Salt and sucrose formulations without Tween 20 dissolved more slowly in a Tween 20 solution than in water alone. In contrast, formulations containing Tween 20 dissolved faster in the Tween 20 solution when compared to dissolution in water.

Determination of dissolution rates of spent fuel in carbonate solutions under different redox conditions with a flow-through experiment

Dissolution rates of spent UO 2 fuel have been investigated using flow-through experiments under oxidizing, anoxic and reducing conditions. For oxidizing conditions, approximately congruent dissolution rates were obtained in the pH range 3–9.3 for U, Np, Ba, Tc, Cs, Sr and Rb. For these elements, steady-state conditions were obtained in the flow rate range 0.02–0.3 ml min −1 . The dissolution rates were about 3 mg d −1 m −2 for pH>6. For pH<6, dissolution rates were strongly increasing for decreasing pH. Incongruent dissolution was found for Zr, Mo, Ru, Rh, Pd, Am and the lanthanides. The dissolution rates with H 2(g) saturated solutions dropped by up to four orders of magnitude as compared to oxidizing conditions. Because of the very low concentrations, only U, Pu, Am, Mo, Tc and Cs could be measured. For anoxic conditions, both the redox potential and dissolution rates increased approaching the same values as under oxidizing conditions.

Influence of Dissolution Medium Agitation on Release Profiles of Sustained-Release Tablets

Reaching nearly perfect sink conditions is very important in the determination of drug dissolution rates. Many times, the only factor that is taken into consideration in achieving sink conditions is the relation between the drug concentration and its solubility. The analytical conditions of the dissolution assay, as well as the dissolution apparatus, stirring speed, and nature and volume of the dissolution fluid may also influence the dissolution results. The main objective of this work was to study the influence of the stirring rate conditions and of the dissolution apparatus in the diltiazem hydrochloride release from tablets. Diltiazem hydrochloride sustained-release (SR) tablets were tested and the following dissolution parameters were evaluated: t10%, t25%, t50%, dissolution time, mean dissolution time (MDT), and dissolution efficiency (DE) at t120, and at t360. To analyze the release mechanism, several release models were tested, such as Higuchi, zero order, first order, Baker-Lonsdale, Hixson-Crowell, Weibull, and Korsmeyer-Peppas. The similarities between two in vitro dissolution profiles were assessed by the similarity factor f2. The in vitro release kinetics of diltiazem hydrochloride sustained-release tablets were evaluated using the USP 2 (paddle) and USP 4 (flow-through) apparatus.

The effect of experiment geometry on the mechanism and rate of dissolution of quartz in basanite at 0.5 GPa and 1350 °C

Mineral dissolution is an important factor in many magmatic processes such as melting, assimilation and magma mixing. Since it is not possible to determine dissolution rates or mechanisms from natural samples, experimental measurements are very useful. However, the geometry of the crystal–melt system can have a large effect on the measured rate, depending on whether the contaminated melt formed during dissolution is gravitationally stable or unstable. This study examines the effects of the crystal–melt geometry on the dissolution rate and mechanism. The experiments were performed using basanite melt and cylinders and spheres prepared from a single crystal of natural quartz. All of the experiments were performed in the piston cylinder apparatus at 0.5 GPa and 1350 °C. Four crystal–melt geometries were used: (1) quartz cylinders on top of a column of melt; (2) quartz cylinders beneath a column of basanite melt; (3) quartz cylinders in the middle of column of melt; (4) quartz spheres on top of a column of basanite melt. These geometries allow an examination of non-convective, convective and mixed non-convective/convective dissolution. Sphere experiments were included, as this has been the most commonly used geometry in previous experimental studies. In all of the experiments quartz dissolves directly into the basanite without formation of cristobalite or tridymite. Quartz on top of a column of melt dissolves at a rate almost proportional to the square root of time and forms a silica-rich compositional boundary layer that is gravitationally stable. All of the samples show well-defined compositional gradients in the boundary layer; however, the melt at the interface varies in composition with time and plots of concentration as a function of distance normalized to time show that the diffusion rate of SiO2 increases with time. These data suggest that the rate-controlling step during quartz dissolution is interface reaction rather than cation diffusion. Quartz on the bottom of a column of basanite dissolves much more quickly than in the quartz-on-top experiments and the dissolution rate is linear, due to the periodic gravitational instability and resultant convection of the boundary layer. Even though interface kinetics are the rate-controlling step in quartz dissolution, convection causes an increase in dissolution rate because it replenishes the boundary layer with new, silica-undersaturated melt, which dissolves the quartz more quickly than the contaminated melt. These data suggest that the interface reaction rate is controlled by the degree of undersaturation of the solvent melt in the dissolving component. Both quartz-in-middle and quartz sphere experiments dissolve at a rate intermediate between the two extremes and both show a power law rate. Both dissolve by a combination of convective and non-convective dissolution but the sphere experiments are affected by an additional factor. During the experiment the sphere can sink through the capsule causing forced convection which adds another complication to the interpretation of the dissolution rate data. The results of this study indicate that the choice of experiment geometry plays a major role in determining the observed dissolution rate. Mineral spheres, which have been widely used in the past, are not ideal for dissolution studies. Instead, dissolution rates and mechanisms are best determined in the absence of convection. These experiments have an additional advantage in that for diffusion-controlled dissolution, they allow determination of cation diffusivity.

First-derivative spectrophotometric and LC determination of cefuroxime and cefadroxil in urine

Two methods are presented for the determination of cefuroxime and cefadroxil in human urine using first ( 1D) derivative spectrophotometry and high-performance liquid chromatography. Cefuroxime and cefadroxil were determined by measurement of their first-derivative amplitude in 0.1 N sodium hydroxide at 292.5 and 267.3 nm, respectively in the concentration range of 2–10 μg ml −1 for each drug. The HPLC method depends upon using a LiChrospher 100 RP-18 (5 μm) column at ambient temperature for cefuroxime and 35°C for cefadroxil with mobile phases consisting of water–acetonitrile–acetic acid (85:15:0.1 v/v) at a flow rate of 1.5 ml min −1 for cefuroxime; and 0.02 M potassium dihydrogen phosphate–acetonitrile (95:5 v/v) containing 0.003% (w/v) hexanesulphonic acid sodium salt and adjusted to apparent pH 3 with phosphoric acid at a flow rate of 2 ml min −1 for cefadroxil. Quantitation was achieved with UV detection at 275 and 260 nm for cefuroxime and cefadroxil, respectively, based on peak area with linear calibration curves at the concentration ranges of 2–10 μg ml −1 for cefuroxime and 5–20 μg ml −1 for cefadroxil. The proposed methods were applied to the determination of dissolution rate for tablets and capsules containing each drug. The urinary excretion patterns as the cumulative amounts excreted have been calculated for each drug using the proposed methods.

Inclusion of ketoprofen with skimmed milk by freeze-drying

Ketoprofen is a non-steroidal anti-inflammatory drug which is not soluble in water and creates gastrointestinal problems. In order to improve the solubility of the drug in water and enhance its dissolution rate, physical mixture (PM) and inclusion (IC) of ketoprofen with skimmed milk (SM) were prepared and investigated. Enhancement of solubility of ketoprofen was obtained by preparing its IC with SM which can be used because of its amino acid and surface active agents content and can also be used for treatment of gastric disturbance. Lyophilization technique was used to prepare the IC. Results obtained showed that the solubility of IC of ketoprofen with SM was almost four times greater than the solubility of the plain drug. Data from the dissolution rate determination have also indicated that IC of ketoprofen with SM significantly improved the dissolution rate of the drug compared with PM and the plain form. Differential scanning calorimetry (DSC), X-ray powder diffraction and scanning electron microscopic (SEM) analysis revealed the formation of IC of ketoprofen with SM.

Investigation of Cyclodextrin Complexes of Mandelic acid

The inclusion complexes of both optically active and racemic mandelic acids with α-, (β- and γ-cyclodextrins were prepared by using a liophylisation technique. The compounds formed were investigated by thermoanalytical methods (TG, DSC and EGD) which were completed with FT-IR spectroscopic measurements, scanning electron microscopic observations, and dissolution rate determinations. The inclusion complex formation between all guests and hosts were proven using the thermoanalytical and FT-IR spectroscopic methods.

Preparation and Evaluation of Sustained-Release Solid Dispersions of Drugs with Eudragit Polymers

Coevaporates of paracetamol and rifampicin with Eudragit polymers of different natures (anionic, cationic, and zwitterionic) were prepared. Determination of dissolution rate of these coevaporates in dissolution media simulating those of the gastrointestinal tract (GIT) revealed that the release rate of paracetamol is retarded from all the coevaporates studied. In this respect, Eudragit L100-SS shows the highest sustainment of drug release, while Eudragit E100 shows the lowest. Conversely, the release of rifampicin from its coevaporates with the anionic Eudragit S100 polymer is more retarded than the corresponding coevaporate with the zwitterionic Eudragit RL100 or from coevaporates with equal mixtures of the two polymers.Increasing the polymer weight fraction in rifampicin coevaporates with Eudragit S100 up to 0.5 resulted in a corresponding decrease in the dissolution rate. However, beyond this weight fraction, the polymer effect on the dissolution rate of the drug becomes minimized. The results confirmed that the process of dissolution of the two drugs from their coevaporates is a diffusion-controlled release process.The biological performance of paracetamol coevaporates was monitored in rabbits; paracetamol level in plasma was found to follow first-order kinetics. for all the investigated paracetamol coevaporates, the peak plasma level was less than 50 μg/ml compared to a value of 60, μg/ml for the drug per se. The coevaporates of the drug with Eudragit L100-55 showed slowest rates of absorption and elimination as well as greatest half-peak and half-life times. Biological peformance of rifampicin coevaporates was assessed in human subjects receiving a single oral dose equivalent to 300 mg of the drug. The results depicted sustainment of drug release as a function of polymer weight fraction. A strict correlation was shown to exist between the total amount of drug excreted during 24 hr post dosing of the coevaporates and its in vitro dissolution rate.The results depicted that paracetamol can be formulated in the form of a coevaporate with Eudragit L100-55 to prepare a more safe sustained-release formulation with minimal side effects, and also revealed the advantages of administration of rifampicin in the form of a coevaporate with Eudragit S100 (4:1) at a single oral dose equivalent to 600 mg of drug.

From Laboratory Experiments to a Geological Disposal Vault: Calculation of Used Nuclear Fuel Dissolution Rates

ABSTRACTCalculation of used nuclear fuel dissolution rates in a geological disposal vault requires a knowledge of the redox conditions in the vault. For redox conditions less oxidizing than those causing UO2 oxidation to the U3O7 stage, a thermodynamically-based model is appropriate. For more oxidizing redox conditions a kinetic or an electrochemical model is needed to calculate these rates. The redox conditions in a disposal vault will be affected by the radiolysis of groundwater by the ionizing radiation associated with the fuel. Therefore, we have calculated the alpha-, beta- and gamma-dose rates in water in contact with the reference used fuel in the Canadian Nuclear Fuel Waste Management Program (CNFWMP) as a function of cooling time. Also, we have determined dissolution rates of UO2 fuel as a function of alpha and gamma dose rates from our electrochemical measurements. These room-temperature rates are used to calculate the dissolution rates of used fuel at 100°C, the highest temperature expected in a container in the CNFWMP, as a function of time since emplacement. It is shown that beta radiolysis of water will be the main cause of oxidation of used CANDU fuel in a failed container. The use of a kinetic or an electrochemical corrosion model, to calculate fuel dissolution rates, is required for a period of ∼ 1000 a following emplacement of copper containers in the geologic disposal vault envisaged in the CNFWMP. Beyond this time period a thermodynamically-based model adequately predicts the fuel dissolution rates. The results presented in this paper can be adopted to calculate used fuel dissolution rates for other used UO2 fuels in other waste management programs.

A Turbidity Study of the Rate of Dissolution of Zinc-Monoglycerolate in Aqueous Solution

Abstract The turbidity of suspensions of polymeric zinc monoglycerolate (ZMG) has been used to determine dissolution rates in aqueous solution. The rate was found to be first order with respect to the concentration of undissolved ZMG and of order 1/2 with respect to the hydrogen ion concentration in the pH range 4.1–5.8 and a temperature range of 20°C - 45°C. The temperature dependence at constant pH obeys the Arrhenius equation and the activation energy of the dissolution process was found to be near 35 k J mol−1.

Control of Poorly Soluble Drug Dissolution in Conditions Simulating the Gastrointestinal Tract Flow. 1. Effect of Tablet Geometry in Buffered Medium

The dissolution rate of a solid drug from the gastrointestinal (GI) tract is affected by the properties and flow dynamics of the liquid medium surrounding the tablet, as well as by the chemical nature of the drug. In this study, naproxen was used as a poorly soluble model drug. The dissolution medium was buffered with acetate, citrate, or phosphate buffer of varied concentrations and pH. GI flow conditions around a stationary tablet were simulated in a laminar flow device by anchoring the tablet on the floor of its channel having a rectangular cross section. Fresh, buffered solution was passed across the tablet and the effluent was collected for analysis and calculation of the dissolution rate. The dissolution rate was found to vary nonlinearly with the exposed tablet height, reaching a maximum at a tablet height approximately half the channel height. This maximum rate was attributed to an optimal combination of (1) eddy mixing and local turbulence generated by the flow impingement on the bluff object (tablet) and (2) the exposed tablet surface area available for dissolution. This effect was further confirmed by using dye-enhanced visual analysis of flow patterns at varied flow rates and exposed tablet heights. Elevation of the tablet to approximately the channel half-height significantly magnified the dissolution rate increase observed on exposure to buffered medium. Thus, tablet height and exposed surface area are major factors in determining dissolution rate, especially in conditions where the dissolving species reacts with the solvent. These results suggest that standard in vitro dissolution rate methods do not qualitatively indicate incremental changes in rate with altered tablet geometry or dissolution medium.

Time-Resolved Raman Measurements of Hydrocarbon Interactions with Poly-α-olefin Films

Laser Raman spectroscopy was used to study the dissolution of volatile hydrocarbon molecules in thin films of poly-α-olefin oil. Above the boiling point of the hydrocarbon, or when no liquid hydrocarbon was present, the dissolution was driven by Henry's law solubilities in line with previous models. However, below the boiling point and when significant liquid hydrocarbon was present, dissolution was entropically driven. Under these conditions, where equilibrium solubilities were not achievable, the Raman spectra were used to determine dissolution rates. Over the range of conditions studied, and particularly for a given class of volatile hydrocarbons, pressure and temperature influenced the dissolution rate primarily by affecting the vapor pressure and concentration of the volatile hydrocarbon. The rate-limiting step for the dissolution involved mass transport at the vapor/film interface.

Solid State Characterization of Dehydroepiandrosterone

Three polymorphs (forms I–III), a monohydrate (form S2), and three new solvates [4:1 hydrate (form S1), monohydrate (form S3), and methanol half‐solvate (form S4)] were isolated and characterized by X‐ray powder diffractometry (XRPD), IR spectroscopy, differential scanning calorimetry (DSC), hot stage microscopy, solution calorimetry, and their dissolution rates. A new polymorph, designated as form V, melting at 146.5–148°C, was observed by hot stage microscopy. Our results indicate that only forms I and S4 exhibit reproducible DSC thermograms. Five of the isolated modifications undergo phase transformation on heating, and their DSC thermograms are not reproducible. Interpretation of DSC thermograms was facilitated by use of hot stage microscopy. The identification of each modification is based on XRPD patterns (except forms S3 and S4, for which the XRPD patterns are indistinguishable) and IR spectra. In the IR spectra, a significant difference was observed in the OH stretching region for all seven modifications. In a purity determination study, 5% of a contaminant modification in binary mixtures of several modifications could be detected by use of XRPD. To obtain a better understanding of the thermodynamic properties of these modifications, a series of increasing heating rates and different pan types were used in DSC. According to Burger's rule, forms I–III are monotropic polymorphs with decreasing stability in the order form I > form II > form III. The melting onsets and heats of fusion for forms I–III are 149.1 °C, 25.5 kJ/mol; 140.8 °C, 24.6 kJ/mol; and 137.8 °C, 24.0 kJ/mol, respectively. For form III the heat of fusion was calculated from heat of solution and DSC data. In the case of form S1 the melting point, 127.2°C, was obtained by DSC using a hermetically sealed pan. The relative stabilities of the six modifications stored under high humidity conditions were predicted to be, on the basis of the heat of solution and thermal analysis data, form S2 > form S3 > form S1 > form I > form II > form III. However, the results of the dissolution rate determination were inconsistent with the heat of solution data. The stable form I shows a higher initial dissolution rate than the metastable form II and unstable form III. All modifications were converted into the stable monohydrate, form S2, during the dissolution study, suggesting that the moisture level in solid formulations should be carefully controlled.

Determination of film-coated tablet parameters by near-infrared spectroscopy

Near-infrared (near-IR) spectroscopy was used in the determination of three parameters of theophylline tablets film-coated with ethylcellulose. Spectra of individual intact tablets were collected on two near-IR spectrometers: a grating-based spectrometer, and an acousto-optic tunable filter spectrometer. Calibrations were developed for the prediction of the time to 50% dissolution ( t 50%) of theophylline for tablets of varying coat thickness, for the determination of the thickness of the ethylcellulose coat applied, and for the prediction of the hardness of coated tablets. Principal component analysis was performed on the spectra prior to calibration development. The standard errors of calibration (SEC) and prediction (SEP) for determination of dissolution rates were 2.8 and 6.6 min, respectively. The SEC for the coating thickness calibration was 0.0002 inches, with an SEP of 0.00024 inches, and the SEC and SEP for the determination of tablet hardness were 0.54 and 0.62 kilopons, respectively.

Effects of Cyclodextrins and Phospholipids in Enhancing Dissolution of Indomethacin

AbstractInclusion complexes of indomethacin (IND) and β-cyclodextrins (β-CD) were prepared by the freeze drying methods. Solid dispersion of IND and Dimyristoylphosphatidylcholine (DMPC) was prepared as coprecipitate (CPPT) by the solvent method. These formulations were characterized by X-ray diffractometry and dissolution rate determinations. Dissolution of IND from β-CD inclusion complex was found to be 133 times faster than the corresponding pure IND, whereas it was about 4 times faster from a DMPC CPPT sample. Various derivatives of β-CDs showed variable rates of dissolution of IND. β-CD and most of the other derivatives showed almost instantaneous dissolution of IND at a molar ratio of 1:1 (IND:β-CD) except dimethyl-β-cyclodextrin (DMB) derivative, which showed a fairly constant release of IND over 90 minutes. DMB may, therefore, have the potential for use in the formulation of a constant-release preparation. X-ray diffraction spectra showed that indomethacin remained as amorphous state in CPPT or in...

Dissolution of Glass Fibers in the Rat Lung Following Intratracheal Instillation

The biopersistence of airborne fibers is felt to play an important role in their potential toxicity. Since the dissolution rate of fibers can be measured in cell-free systems, the current study was undertaken to determine if the dissolution rate of fibers in the lung was related to the dissolution rate of fibers in vitro, and whether dissolution serves to remove fibers from the lung. To determine dissolution rates in vivo, suspensions of fibers were administered to rats by intratracheal instillation, and the numbers, lengths, and diameters of fibers recovered from the lungs at intervals up to 1 yr after administration were measured by phase-contrast optical microscopy. Five different glass fibers were used that had dissolution rates ranging from 2 to 600 ng/cm2/h measured in vitro in simulated lung fluid at pH 7.4. Examination of the diameter distributions of fibers longer than 20 μm showed that the peak diameter decreased steadily with time after instillation, at the same rate measured for each fiber in vitro, until it approached zero. Measurements of the total number of fibers remaining in the rats' lungs at times up to 1 yr after instillation suggest that not many of the administered fibers were being cleared by macrophage-mediated transport via the conducting airways. A computer simulation of the fibers in the lungs was performed in which each of the administered long fibers (20 μm or longer) was decreased in diameter according to the rate measured in vitro, while the short fibers (less than 20 μm long) were unaffected. The ratio of long to short fibers predicted by this simulation agreed well with this quantity measured from the fibers recovered from the rats' lungs at each time interval after instillation. It was concluded that long glass fibers, at least those longer than 20 μm, are removed from the lung by dissolution at much the same rate measured in vitro.