Reduction In Dissolution Rate Research Articles

Utilization of In Vitro, In Vivo and In Silico Tools to Evaluate the pH-Dependent Absorption of a BCS Class II Compound and Identify a pH-Effect Mitigating Strategy.

To describe a stepwise approach to evaluate the pH effect for a weakly basic drug by in vitro, in vivo and in silico techniques and identify a viable mitigation strategy that addresses the risk. Clinical studies included assessment of the pH effect with famotidine. In vitro dissolution was evaluated in various biorelevant media and in a pH-shift test. PK studies in dogs were conducted under pentagastrin or famotidine pre-treatment and GastroPlus was employed to model human and dog PK data and simulate the performance in human. Clinical data indicated considerable pH dependent absorption of the drug when dosed in the presence of H2-antagonists. In vitro dissolution and in vivo dog data confirmed that the observed pH effect was due to reduced dissolution rate and lower solubility at increased gastric and intestinal pH. A salt form was identified to overcome the effect by providing fast dissolution and prolonged supersaturation. GastroPlus simulations predicted a mitigation of the pH effect by the salt. The drug exhibited a strong pH-effect in humans. The in vitro, in vivo and modeling approach provides a systematic workflow to evaluate the risk of a new drug and identify a strategy able to mitigate the risk.

Evaluation of food effect on the oral absorption of clarithromycin from immediate release tablet using physiological modelling.

Food may affect the oral absorption of drugs. The aim of the present study was to investigate the influence of food on the oral absorption of clarithromycin by evaluating the effect of media parameters, such as pH, bile secretions and food composition, on the release of the drug from immediate release tablets, using in vitro and in silico assessments. The solubility, disintegration and dissolution profiles of clarithromycin 500mg immediate release tablets in compendial media with/without the addition of a homogenized FDA meal as well as in biorelevant simulated intestinal media mimicking fasting and fed conditions were determined. These in vitro data were input to GastroPlus™, which was used for developing a physiological absorption model capable of anticipating the effect of food on clarithromycin absorption. Level A in vitro-in vivo linear correlations were established using a mechanistic absorption modelling based deconvolution approach. The pH of the media has a profound effect on clarithromycin solubility, tablet disintegration and drug release. Clarithromycin has lower solubility in biorelevant media compared with other media, due to complex formation with bile salts. Clarithromycin tablets exhibited prolonged disintegration times and reduced dissolution rates in the presence of the standard FDA meal. The simulation model predicted no significant food effect on the oral bioavailability of clarithromycin. The developed IVIVC model considered SIF, acetate buffer and FaSSIF media to be the most relevant from the physiological standpoint. The intake of a standard FDA meal may have no significant effect on the oral bioavailability of clarithromycin immediate release tablet.

Monte Carlo analysis of montmorillonite particle structures and modeling of dissolution rate reduction

The equilibrium structure of montmorillonite clay particles was calculated using Monte Carlo simulation to evaluate the long-term behavior of alteration for bentonite buffer materials in geological repositories of radioactive waste. It has been experimentally observed that the dissolution rate of montmorillonite strongly decreases as the density increases. One of the primary causes of this reduction in dissolution rate is the reduction in reactive surface area when the edges of particles are covered with other particles (physical masking). In this study, we proposed a geometrical model in which the masking area (the edge surface masked by other particles) is calculated from the edge-to-face distance of particles. The effective edge surface area (ESA) from the equilibrium structure obtained from Monte Carlo simulation was computed using the masking model. The numerical results of the effective ESA are in good agreement with the experimental measurements of the dissolution rate by atomic force microscopy in a wide range of density conditions. Moreover, we propose a prediction expression of the effective ESA of montmorillonite particles over a wide range of density conditions, which produces physically reasonable predictions.

Entrapment and Dissolution of Microbubbles Inside Microwells.

The formation and evolution of immersed surface micro- and nanobubbles are essential in various practical applications, such as the usage of superhydrophobic materials, drug delivery, and mineral flotation. In this work, we investigate the entrapment of microbubbles on a hydrophobic surface, structured with microwells, when water flow passes along, and the subsequent microbubble dissolution. At entrapment, the microbubble is initially pinned at the edge of the microwell. At some point, the three-phase contact line detaches from one side of the edge and separates from the wall, after which it further recedes. We systematically investigate the evolution of the footprint diameter and the contact angle of the entrapped microbubbles, which reveals that the dissolution process is in the constant contact angle mode. By varying the gas undersaturation level, we quantify how a high gas undersaturation enhances the dissolution process, and compare with simplified theoretical predictions for dissolving bubbles on a plane surface. We find that geometric partial blockage effects of the diffusive flux out of the microbubble trapped in the microwell lead to reduced dissolution rates.

Beads-on-String-Shaped Poly(azomethine) Applicable for Solution Processing of Bilayer Devices Using a Same Solvent.

Solvent-based deposition techniques for fabrication of organic field-effect transistors (OFETs) generally require orthogonal solvents for deposition of a conjugated polymer layer on a polymer gate insulator layer. Here, we found significantly reduced dissolution rate of the polymeric film in the same solvent after casting a homegeneous polymerization solution of para-bis(3-aminopropyl)hexaisobutyl-substituted T8 cage (1) with terephthalaldehyde. The limited dissolution rate in the solvent provided enough chance for fabrication of a regioregular poly(3-hexylthiophene-2,5-diyl) (P3HT) layer on the present polymer films without using an orthogonal solvent. The rheological properties indicate that physical interaction between the polymer chains provides the significantly reduced dissolution rate after the deposition onto a substrate without any cross-linking treatments.

Preparation and characterization of solid dispersions of celecoxib obtained by spray-drying ethanolic suspensions containing PVP-K30 or isomalt

Celecoxib (CLX) is an anti-inflammatory drug that is used for acute pain treatment, but it has very low oral bioavailability owing to its poor water solubility. In this study, CLX solid dispersions are prepared by spray-drying using hydrophilic carriers with the aim of improving its apparent solubility and dissolution rate. Blends with different ratios of CLX, isomalt (ISO) and PVP were prepared in ethanol, and solid dispersions were obtained using a spray dryer. The saturation solubility and dissolution kinetics in 0.25% SLS and 0.04 M Na3PO4 containing media were determined. Also, SEM, DSC, XRPD, and stability studies were used to characterize the systems. Physicochemical analysis demonstrated the presence of amorphous CLX in the spray dried samples. The saturation solubility and dissolution rate of CLX from these formulations were higher than those for pure celecoxib and its physical mixtures. Amorphous CLX showed a lower dissolution rate compared to its crystalline form in 0.25% SLS medium, while this tendency was reversed under alkaline conditions. The CLX:PVP:ISO 3:5:2 spray dried sample showed the highest dissolution rate in both media. Exposure of samples to high moisture (75% humidity) recrystallized some of the amorphous CLX. Thus, the results showed that the dissolution rate of CLX was enhanced in 0.25% SLS, whereas a reduction in dissolution rate was observed in 0.04 M Na3PO4.

Are Excipients Inert? Phenytoin Pharmaceutical Investigations with New Incompatibility Insights.

The U.S. Pharmacopeia defines excipients as substances other than the active pharmaceutic ingredient (API) that are added in a drug delivery system in order to aid in the manufacturing process and enhance stability, bioavailability, safety, effectiveness and delivery of the drug. The 1968 phenytoin intoxication outbreak in Brisbane, Australia, is a classic example of an API-excipient interaction. When administered with CaSO4 the absorption of phenytoin was reduced due to an interaction between the API and the excipient. When CaSO4 was replaced by lactose, the amount of drug absorbed was much higher, resulting in the observed intoxication. It was hypothesized that phenytoin was converted to a calcium salt prior to ingestion. The purpose of this study was to mechanistically investigate the interactions between excipients and phenytoin to confirm the hypothesis of the previous reports. Titration experiments with phenytoin and calcium salt were performed. Isothermal micro calorimetry was used to determine incompatibilities between excipients, phenytoin and milk. NMR was used to characterize the compounds. Dissolution tests containing CaSO4, lactose or sorbitol as excipients were also performed. Both Canadian and United States of America commercially available capsules were tested with milk and water. The calorimeter results indicate that phenytoin sodium interacts with CaSO4 in aqueous media and the dissolution profile of CaSO4 containing capsules showed a reduced dissolution rate. In addition, phenytoin sodium also interacts with lactose through a Maillard reaction that can occur at body temperature. Likewise, commercial Phenytoin sodium products interacted with milk and the products containing lactose showed browning in water. In Canada and the USA, the reference product contains lactose as an excipient in the formulation, whereas the Canadian generic formulations do not contain lactose. Any clinical relevance of these difference has not been determined. A new incompatibility between phenytoin and lactose has been discovered and an incompatibility with calcium was confirmed, which may have implications in regard to excipients and food effects.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Period of Oscillatory Motion of a Camphor Boat Determined by the Dissolution and Diffusion of Camphor Molecules.

Here, we investigated the oscillatory motion of a camphor boat on water to clarify how the dynamics of camphor concentration profile determines the period of oscillation. The boat, which was made of a plastic plate and a camphor disk, was glued below the plate at a distance from the edge. The dependence of oscillation period on temperature and viscosity of the water phase was measured in experiments. We reproduced the experimental results by calculating the period of oscillatory motion by considering the experimental values of physicochemical parameters describing the time evolution of camphor concentration profile and the friction acting on a boat, such as diffusion and dissolution rates of camphor, viscosity of the water phase, and the threshold concentration of camphor necessary to accelerate the boat from the resting state. The increase in the period of oscillatory motion at low temperatures was explained by the reduced dissolution rate of camphor into the water phase.

Insights into the Dissolution Kinetics of NaLAS Tablets

AbstractIn this work, the dissolution behaviors of a series of sodium alkylbenzenesulfonates (NaLAS) tablets with different moisture contents and neutralization degrees were investigated in aqueous solution. The ANOVA‐based, model‐independent and model‐dependent methods were employed to perform comparison analyses on dissolution profiles. The measurements of powder X‐ray diffraction patterns and mechanical properties elucidate distinct differences in each formula. The results show that ANOVA provides a possibility for finding the source of differences among different variables, and the model‐independent methods including the k values and mean dissolution time are easy to interpret and perform comparison analyses. The Hixson–Crowell model gives satisfactory correlation results for the dissolution data and the dissolution kinetics parameters are obtained. The inhibition effects of neutralization degree and moisture content on NaLAS dissolution were examined, which reveals that the increase in lamellar phase proportion leads to the reduction of dissolution rate. The comparison analyses performed in this work form part of a methodology for dissolution profile prediction and comparison.

Food effect: The combined effect of media pH and viscosity on the gastrointestinal absorption of ciprofloxacin tablet

BackgroundThe clinical implications of food-drug interactions may have to be taken seriously into account with oral drugs administration in order to minimize variations in drug bioavailability. Food intake may alter physiological changes in the pH and viscosity of the gastrointestinal lumen, which could affect the oral absorption of drugs. PurposeThe aim of the present study was to have an insight on the effect of media parameters: viscosity and pHon the oral absorption of ciprofloxacin HCl from solid formulations using a model food: Corchorus olitorius (Jute) Soup. MethodsIn vitro disintegration and dissolution rates of ciprofloxacin tablet were evaluated using compendia buffer media in the presence/absence of C. olitorius leaves. These in vitro data were then input to GastroPlus™ to predict ciprofloxacin absorption profiles under fasted and fed states. ResultsThe present study demonstrated the significance of luminal pH and viscosity on the dissolution and disintegration of solid formulations following postprandial ingestion of the viscous soup. The tablets showed prolonged disintegration times and reduced dissolution rates in this soup, which could be attributed to the postprandial elevation in media viscosity and reduced solubility at elevated gastricpH. The predicted model under fed state showed no impact on AUC but prolonged Tmax and a decrease in Cmax. ConclusionConcomitant intake of C. olitorius soup with ciprofloxacin might have negative effect on the rate of drug release from conventional immediate release tablets.

Characterization of Thin Film Dissolution in Water with in Situ Monitoring of Film Thickness Using Reflectometry.

Reflectometry was implemented as an in situ thickness measurement technique for rapid characterization of the dissolution dynamics of thin film protective barriers in elevated water temperatures above 100 °C. Using this technique, multiple types of coatings were simultaneously evaluated in days rather than years. This technique enabled the uninterrupted characterization of dissolution rates for different coating deposition temperatures, postdeposition annealing conditions, and locations on the coating surfaces. Atomic layer deposition (ALD) SiO2 and wet thermally grown SiO2 (wtg-SiO2) thin films were demonstrated to be dissolution-predictable barriers for the protection of metals such as copper. A ∼49% reduction in dissolution rate was achieved for ALD SiO2 films by increasing the deposition temperatures from 150 to 300 °C. ALD SiO2 deposited at 300 °C and followed by annealing in an inert N2 environment at 1065 °C resulted in a further ∼51% reduction in dissolution rate compared with the nonannealed sample. ALD SiO2 dissolution rates were thus lowered to values of wtg-SiO2 in water by the combination of increasing the deposition temperature and postdeposition annealing. Thin metal films, such as copper, without a SiO2 barrier corroded at an expected ∼1-2 nm/day rate when immersed in room temperature water. This measurement technique can be applied to any optically transparent coating.

Controlling the burst release of amorphous drug–polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains

High-payload amorphous drug–polysaccharide nanoparticle complex (or nanoplex in short) represents a new class of supersaturating drug delivery systems intended for bioavailability enhancement of poorly-soluble drugs. Not unlike other nanoscale amorphous formulations, the nanoplex exhibits fast dissolution characterized by a burst drug release pattern. While the burst release is ideal for supersaturation generation in the presence of crystallization inhibitor, it is not as ideal for passive targeting drug delivery applications in which the nanoplex must be delivered by itself. Herein we developed nanoplex exhibiting controlled release via crosslinking of the polysaccharide chains onto which the drug molecules were electrostatically bound to. Curcumin and chitosan were used, respectively, as the drug and polysaccharide models with amine-reactive disuccinimidyl tartrate as the crosslinking agent. The crosslinked nanoplex exhibited improved morphology (i.e. smaller size, more spherical, and higher uniformity) that signified its more condensed structure. A twenty-fold reduction in the initial burst release rate with a threefold reduction in the overall dissolution rate was obtained after crosslinking. The slower dissolution was attributed to the more condensed structure of the crosslinked nanoplex that enhanced its dissociation stability in phosphate buffered saline. The reduction in the dissolution rate was proportional to the degree of crosslinking that was governed by the crosslinker to amine ratio. The crosslinking caused slight reductions in the payload and zeta potential of the nanoplex, but with no adverse effect on the cytotoxicity. This proof-of-concept study successfully demonstrated the use of polysaccharide crosslinking to control the drug release from high-payload amorphous drug nanoplex.

A silica-supported solid dispersion of bifendate using supercritical carbon dioxide method with enhanced dissolution rate and oral bioavailability

In this study, to enhance the dissolution rate and oral bioavailability of bifendate, a silica-supported solid dispersion (SD) of bifendate was prepared using supercritical carbon dioxide (ScCO2) technology. The properties of bifendate-silica SD were characterized by differential scanning calorimetry (DSC), X-ray diffraction (X-RD) and scanning electron microscopy. The pharmacokinetic study was carried out in beagle dogs using commercial bifendate dropping pills as a reference which is a conventional SD formulation of bifendate and PEG6000. A novel method of Ultra Performance Convergence Chromatography-tandem mass spectrometry (UPC2™-MS/MS) method was applied to determine bifendate concentration in plasma. The amorphous state of bifendate in bifendate-silica SD was revealed in X-RD and DSC when the ratios of bifendate and silica were 1:15 and 1:19, respectively. In vitro dissolution rate was significantly improved with cumulative release of 67% within 20 min relative to 8% for the physical mixture of bifendate and silica, and which was also higher than the commercial dropping pill of 52%. After storage at 75% relative humidity (RH) for 10 d, no recrystallization was found and reduced dissolution rate was obtained due to the absorption of moisture. In pharmacokinetic study, Cmax and AUC0–t for bifendate-silica SD were 153.1 ng/ml and 979.8 ng h/ml, respectively. AUC0–t of bifendate-silica SDs was ∼1.6-fold higher than that of the commercial dropping pills. These results suggest that adsorbing bifendate onto porous silica via ScCO2 technique could be a feasible method to enhance oral bioavailability together with a higher dissolution rate.

Synthesis and characterization of a new generation of inhibitive pigment based on zinc acetate/benzotriazole: Solution phase and coating phase studies

An organic/inorganic hybrid corrosion inhibitive pigment based on zinc acetate/benzotriazole was synthesized. The chemical composition of the pigment was investigated by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. In addition, the morphology of the pigment was studied by scanning electron microscopy. The pigment solubility in 3.5 wt.% NaCl solution was characterized by UV–Visible, total carbon content and inductively coupled plasma-optical emission spectrometer analyses. The corrosion inhibition properties of the zinc acetate/benzotriazole was compared with conventional zinc phosphate pigment in 3.5 wt.% NaCl solution containing pigments extracts on mild steel samples by polarization test and electrochemical impedance spectroscopy. X-ray photoelectron spectroscopy and scanning electron microscopy characterizations were performed on the steel samples exposed to the extracts to investigate the surface chemistry and morphology of the pigment, respectively. Also, the effects of addition of zinc acetate/benzotriazole and zinc phosphate pigments on the corrosion protection performance of the epoxy coating were studied. Results obtained from X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy analyses confirmed that a complex of Zn-benzotriazole was successfully synthesized. The zinc acetate/benzotriazole pigment showed good solubility in NaCl solution and released inhibitive species including benzotriazole and Zn2+ cations. Zinc acetate/benzotriazole pigment showed good inhibitive properties and reduced dissolution rate of steel through forming Fe-benzotriazole and Zn-benzotriazole complexes, and Zn(OH)2 on the cathodic sites. Also, zinc acetate/benzotriazole enhanced the corrosion protection performance of the epoxy coating and reduced cathodic delamination rate of the coating more than zinc phosphate pigment.

Self-nanoemulsifying particles of coenzyme Q10 with improved nutraceutical potential

The major purpose of the present study was to clarify the physicochemical and nutraceutical properties of self-nanoemulsifying particles of coenzyme Q10 (CoQ10/SNEP). Nanoemulsion preconcentrate, containing CoQ10, medium-chain triglyceride, sucrose ester of fatty acid, and hydroxypropyl cellulose, was spray-dried to produce the CoQ10/SNEP. The CoQ10/SNEP was stored at 40°C with or without 75% relative humidity (RH) for 4 weeks, and its physicochemical properties were characterized in terms of appearance, crystallinity, thermal behavior, dissolution, and self-nanoemulsifying potency. The hepatoprotective effects of CoQ10 and the CoQ10/SNEP were also assessed in a rat model of acute liver injury. Under accelerated conditions (40°C/75% RH), the CoQ10/SNEP was found to be physicochemically unstable, as evidenced by partial deliquescence, slight degradation, reduced dissolution rate, and larger particle size of resultant micelles. In contrast, there appeared to be no significant transition in physicochemical properties of the CoQ10/SNEP after 4 weeks of storage at 40°C. The outcomes from stability testing suggested that moisture protection would be needed for long-term storage of the CoQ10/SNEP. In a rat model of acute liver injury, pretreatment with CoQ10/SNEP (100mg CoQ10/kg, twice) resulted in marked attenuation of hepatic damage as evidenced by decreases of alanine aminotransferase and aspartate aminotransferase, surrogate biomarkers for hepatic injury, by 96% and 82%, respectively, although crystalline CoQ10 was less effective. From these findings, the self-nanoemulsifying approach might be efficacious for improving the nutraceutical values of CoQ10.

Effect of HPMC concentration on crystal habit of nifedipine

Non-polar surface area increased and polar energy decreased resulting in reduction in dissolution rate upon increasing HPMC concentration, from 0% w/v (Nif-0) to 0.6% w/v (Nif-6).

Nanoparticle impacts reveal magnetic field induced agglomeration and reduced dissolution rates.

Superparamagnetic nanoparticles (NPs) are used in a variety of magnetic field-assisted chemical and medical applications, yet little of their fate during magnetic field interrogation is known. Here, fundamental and new insights in this are gained by cathodic particle coulometry. This methodology is used to study individual Fe3O4 NPs in the presence and absence of a magnetic field. It is first noticed that no major NP agglomeration occurs in the absence of a magnetic field even in a suspension of high ionic strength. In contrast, a significant magnetic field-induced agglomeration of NPs is observed in a magnetic field. A second new finding is that the dissolution of Fe3O4 NPs is strongly inhibited in a magnetic field. This is explained as a result of the magnetic field gradient force trapping the released Fe(2+) ions near the surface of a magnetized Fe3O4 NP and thus hindering the mass-transport controlled NP dissolution. Consequently, fundamental magnetic field effects are measured and quantified on both the single NP scale and in suspension and two novel effects are discovered.

Dissolution of dehydroxylated lizardite at flue gas conditions: I. Experimental study

The direct mineralization of flue gas CO2 yields serviceable carbonates, thus combining CO2 utilization with its permanent storage. Such a process requires the rapid dissolution of a magnesium or calcium source at lean operating conditions. Motivated by its worldwide abundance, we have studied the dissolution kinetics of a lizardite-type serpentine that was 75% dehydroxylated by thermal pretreatment to maximize its reactivity. A continuous stirred liquid and gas flow-through setup was designed to perform far-from-equilibrium dissolution experiments at moderate temperatures (30°C⩽T⩽120°C),lowCO2 partial pressures (0.1bar⩽pCO2⩽2bar), using two different particle size fractions, and using a mineral acid instead of CO2 to vary the solution pH. Dissolution was measured to be non-stoichiometric and did not reach steady state within 10h. Up to 83% of the magnesium (Mg) and 72% of the silicon (Si) dissolved within the first 100min, where the dissolution rate for both Mg and Si increased with temperature and pCO2. This fast stage was followed by a period with much reduced dissolution rates. The key observations are rationalized with regard to the physical morphology and chemical properties of the thermally activated mineral, and discussed in view of the design of a process that combines CO2 capture and storage by mineralization.

Assessing the Risk of pH-Dependent Absorption for New Molecular Entities: A Novel in Vitro Dissolution Test, Physicochemical Analysis, and Risk Assessment Strategy

Weak base therapeutic agents can show reduced absorption or large pharmacokinetic variability when coadministered with pH-modifying agents, or in achlorhydria disease states, due to reduced dissolution rate and/or solubility at high gastric pH. This is often referred to as pH-effect. The goal of this study was to understand why some drugs exhibit a stronger pH-effect than others. To study this, an API-sparing, two-stage, in vitro microdissolution test was developed to generate drug dissolution, supersaturation, and precipitation kinetic data under conditions that mimic the dynamic pH changes in the gastrointestinal tract. In vitro dissolution was assessed for a chemically diverse set of compounds under high pH and low pH, analogous to elevated and normal gastric pH conditions observed in pH-modifier cotreated and untreated subjects, respectively. Represented as a ratio between the conditions, the in vitro pH-effect correlated linearly with clinical pH-effect based on the Cmax ratio and in a non-linear relationship based on AUC ratio. Additionally, several in silico approaches that use the in vitro dissolution data were found to be reasonably predictive of the clinical pH-effect. To explore the hypothesis that physicochemical properties are predictors of clinical pH-effect, statistical correlation analyses were conducted using linear sequential feature selection and partial least-squares regression. Physicochemical parameters did not show statistically significant linear correlations to clinical pH-effect for this data set, which highlights the complexity and poorly understood nature of the interplay between parameters. Finally, a strategy is proposed for implementation early in clinical development, to systematically assess the risk of clinical pH-effect for new molecular entities that integrates physicochemical analysis and in vitro, in vivo and in silico methods.

The Effect of Monoalkyl Phosphates and Fluoride on Dissolution of Hydroxyapatite, and Interactions with Saliva

The aims were to investigate the effect of monoalkyl phosphates (MAPs) and fluoride on dissolution rate of native and saliva-coated hydroxyapatite (HA). Fluoride at 300 mg/l (as NaF) inhibited dissolution of native HA by 12%, while potassium and sodium dodecyl phosphates (PDP, SDP), at 0.1% or higher, inhibited dissolution by 26-34%. MAPs, but not fluoride, also showed persistence of action. MAPs at 0.5% and fluoride at 300 mg/l were then tested separately against HA pre-treated with human saliva for 2 or 18 h. Agents were applied with brushing to half the specimens, and without brushing to the other half. In control (water-treated) specimens, pre-treatment of HA with human saliva reduced dissolution rate on average by 41% (2 h) and 63% (18 h). Brushing did not have a statistically significant effect on dissolution rate of saliva-coated specimens. In brushed specimens, fluoride significantly increased the inhibition due to 2- or 18-hour saliva pre-treatment. It is hypothesised that brushing partially removes the salivary film and allows KOH-soluble calcium fluoride formation at the surfaces of HA particles. Inhibition was reduced by PDP in 2-hour/non-brushed specimens and in 18-hour/brushed specimens. PDP did not affect dissolution rates in the remaining groups and SDP did not affect dissolution rate in any group. Possible reasons for these variable results are discussed. The experiments show that pre-treatment with saliva can significantly modify results of tests on potential anti-erosive agents and it is recommended that saliva pre-treatment should be a routine part of testing such agents.