Solid Dispersions Of Polyethylene Glycol Research Articles

Solubility and dissolution enhancement of flurbiprofen by solid dispersion using hydrophilic carriers

ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05) in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%). The mean dissolution time (MDT) was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min.) indicating faster drug release. The DE (% dissolution efficiency) was increased by 2.5 folds (61.63%) compared to conventional tablets (23.71%). From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.

Preparation and characterization of pelletized solid dispersion of resveratrol with mesoporous silica microparticles to improve dissolution by fluid-bed coating techniques

With hydrophilic surface and high surface area, porous silica has been applied to load insoluble drugs. Compared to solvent equilibrium method, resveratrol (RES)–mesoporous silica microparticles (MSM) solid dispersion prepared by fluid bed demonstrated higher drug loading and more complete dissolution. Pore volume and diameter have more remarkable effects than surface area to the drug loading and in vitro dissolution profiles. RES–polyethylene glycol solid dispersion with high drug loading showed fast but incomplete dissolution due to the recrystallization. The combination of fluid bed and MSM was an effective strategy to improve drug loading as well as dissolution for poorly water-soluble drugs.

Characterization and Solubility Study of Norfloxacin-Polyethylene Glycol, Polyvinylpyrrolidone and Carbopol 974p Solid Dispersions

Norfloxacin has a low aqueous solubility which leads to poor dissolution. Keeping this fact in mind the purpose of the present study is to formulate and evaluate norfloxacin solid dispersion. Solid dispersions were prepared using hydrophilic carriers like polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974pNF (CP) in various ratios using solvent evaporation technique. These formulations were evaluated using solubility studies, dissolution studies; Fourier transmitted infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetery (DSC). The influence of polymer type and drug to polymer ratio on the solubility and dissolution rate of norfloxacin was also evaluated. FTIR analysis showed no interaction of all three polymers with norfloxacin. The results from XRD and DSC analyses of the solid dispersion preparations showed that norfloxacin existsin its amorphous form. Among the Norfloxacin: PEG solid dispersions, Norfloxacin: PEG 1:14 ratio showed the highest dissolution rate at pH 6.8. For norfloxacin: PVP solid dispersions, norfloxacin: PVP 1:10 ratio showed the highest dissolution rate at pH 6.8. For Norfloxacin: CP solid dispersions, norfloxacin: P 1:2 ratio showed the highest dissolution rate at pH 6.8. The solid dispersion of norfloxacin with polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974p NF (CP), lends an ample credence for better therapeutic efficacy.

Physicochemical characterization of nimodipine–polyethylene glycol solid dispersion systems

This study investigates the solid–solid interactions between nimodipine (NIM) and polyethylene glycol (PEG) of different mean molecular weights (PEG 2000, 4000 and 6000), in solid dispersion systems, applying differential scanning calorimetry (DSC), Fourier-Transform infrared spectroscopy, powder X-ray diffraction (PXRD), hot stage microscopy (HSM) and theoretical modeling by the Flory–Huggins (FH) solution theory. Phase diagrams constructed with the aid of DSC and FH solution theory showed sensitivity on the estimated values of the FH interaction parameter (χ). When χ is considered a constant number (χ = α, α ≠ 0), formation of a eutectic mixture is predicted in the 70–80% w/w PEG concentration region, while when χ was considered as a function of concentration and temperature (χ = f(φ,Τ)), the model predicts the formation of monotectic systems. Construction of more precise phase diagrams by HSM to the aid of Kofler’s “contact preparation” method confirmed the monotectic nature of the examined systems. Studies on NIM’s re-crystallization process in the solid dispersions revealed a strong dependence of the crystallization rate, as well as the resulting crystal form, on the mean molecular weight and concentration of PEG: NIM crystallization rates decrease as PEG’s MW increases, while NIM mod II crystals predominate in dispersions prepared at temperatures above NIM’s liquidus and growth of NIM mod I prevailing in PEG-rich samples.

Solid dispersions in the development of a nimodipine floating tablet formulation and optimization by artificial neural networks and genetic programming

The present study investigates the use of nimodipine–polyethylene glycol solid dispersions for the development of effervescent controlled release floating tablet formulations. The physical state of the dispersed nimodipine in the polymer matrix was characterized by differential scanning calorimetry, powder X-ray diffraction, FT-IR spectroscopy and polarized light microscopy, and the mixture proportions of polyethylene glycol (PEG), polyvinyl-pyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), effervescent agents (EFF) and nimodipine were optimized in relation to drug release (% release at 60 min, and time at which the 90% of the drug was dissolved) and floating properties (tablet’s floating strength and duration), employing a 25-run D-optimal mixture design combined with artificial neural networks (ANNs) and genetic programming (GP). It was found that nimodipine exists as mod I microcrystals in the solid dispersions and is stable for at least a three-month period. The tablets showed good floating properties and controlled release profiles, with drug release proceeding via the concomitant operation of swelling and erosion of the polymer matrix. ANNs and GP both proved to be efficient tools in the optimization of the tablet formulation, and the global optimum formulation suggested by the GP equations consisted of PEG = 9%, PVP = 30%, HPMC = 36%, EFF = 11%, nimodipine = 14%.

Characterisation of Gliclazide-PEG 8000 Solid Dispersions

Purpose : The aim of the present study was to characterise gliclazide solid dispersions (SDs) prepared with polyethylene glycol (PEG) 8000 and compare them with SDs in PEG 6000. Methods : Gliclazide SDs containing varying concentrations of PEG 8000 were prepared using the fusion – solvent technique, and their phase solubility behavior and dissolution in 0.1N HCl were assessed at 37 o C. The physical state of, and gliclazide-PEG interactions in, SDs and physical mixtures prepared in ratios of 1:1, 1:2 and 1:5 (gliclazide: PEG 8000), respectively, were characterized by x-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). Results : The solubility of gliclazide increased with increasing amount of PEG 8000 in aqueous medium. Gibbs free energy ( �G o tr ) values were all negative, indicating the spontaneous nature of gliclazide solubilisation. Dissolution studies indicated a significant increase in the dissolution of gliclazide when dispersed in PEG 8000. FTIR analysis demonstrated the absence of well-defined gliclazide - PEG 8000 chemical interaction while DSC and XRD studies indicated the amorphous /microcrystalline state of gliclazide in the SDs. Conclusion : In both solid dispersions and physical mixture, PEG 8000 increases the solubility and dissolution rate of gliclazide. The increased dissolution rate of gliclazide may be due to the formation of microcrystals, increased wettability and dispersibility in systems containing PEG 8000.

Characterization of the distribution, polymorphism, and stability of nimodipine in its solid dispersions in polyethylene glycol by micro-Raman spectroscopy and powder x-ray diffraction

In the present study, a series of solid dispersions of the drug nimodipine using polyethylene glycol as carrier were prepared following the hot-melt method. Micro-Raman spectroscopy in conjunction with X-ray powder diffractometry was used for the characterization of the solid structure, including spatial distribution, physical state, and presence of polymorphs, as well as storage stability of nimodipine in its solid formulations. The effect of storage time on drug stability was investigated by examination of the samples 6 months and 18 months after preparation. Confocal micro-Raman mapping performed on the samples showed that the drug was not uniformly distributed on a microscopic level. The presence of crystals of nimodipine with sizes varying between one and several micrometers was detected, and the crystal size seemed to increase with overall drug content. In samples examined 6 months after preparation it was found that the crystals existed mainly as the racemic compound, whereas after 18 months of storage mainly crystal conglomerates were observed.

Characterization and Dissolution Properties of Ketoprofen in Binary and Ternary Solid Dispersions with Polyethylene Glycol and Surfactants

The effect of incorporation of an anionic [sodium dodecyl sulfate (SDS) or dioctylsulfosuccinate (DSS)] or nonionic [Tween 60 (TW60)] surfactant on the properties of ketoprofen solid dispersions in polyethylene glycol 15000 (PEG) has been investigated. Physicochemical and morphological properties of the various solid systems were determined by differential scanning calorimetry, hot stage microscopy, X-ray powder diffraction analysis, and scanning electron microscopy. The results from dissolution studies, performed according to the USP 24 basket method, indicated that all ternary dispersed systems were significantly (p < 0.001) more efficacious than the corresponding binary ones, by virtue of the additive wetting and solubilizing effect due to the presence of the surfactant. The relative effectiveness of the incorporated surfactant was in the same order as found in phase-solubility studies (i.e., SDS > DSS > TW60). With regard to the solid dispersion preparation method, coevaporated products always gave better results than the corresponding cofused ones; however, this effect was statistically significant (p < 0.001) only in the initial phase of the dissolution process. The most effective solid dispersion was the 10-80-10 w/w drug-PEG-SDS ternary coevaporate, which allowed dissolution of 50% drug after only 6 min (in comparison with > 120 min for drug alone and 17 min for the binary coevaporate) and dissolution of about 100% drug after 30 min (in comparison with > 120 min for the binary coevaporate).

Evaluation of Solid Dispersions of Clofazimine

ABSTRACTClofazimine (CLF) was formulated with polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) as a solid solid dispersion (SSD) to increase the aqueous solubility and dissolution rate of the drug. Different molecular weights of PEG (1500, 4000, 6000, and 9000 Da) and PVP (14,000 and 44,000 Da) were used in different drug:carrier weight ratios (1:1, 1:5, and 1:9) and their effect on the dissolution performance of the drug was evaluated in USP Type 2 apparatus using 0.1 N HCl medium. The dissolution rate was compared with corresponding physical mixtures, a currently marketed soft gelatin capsule product, and free CLF. The effect of different methods of preparation (solvent/melt) on the dissolution rate of CLF was evaluated for PEG solid dispersions. Saturation solubility and phase solubility studies were carried out to indicate drug:carrier interactions in liquid state. Infrared (IR) spectroscopy and X-ray diffraction (XRD) were used to indicate drug:carrier interactions in solid state. Improvement in the drug dissolution rate was observed in solid dispersion formulations as compared to the physical mixtures. The dissolution rate improved with the decreasing weight fraction of the drug in the formulation. Polyvinyl pyrrolidone solid dispersion systems gave a better drug release profile as compared to the corresponding PEG solid dispersions. The effect of molecular weight of the PEG polymers did not follow a definite trend, while PVP 14,000 gave a better dissolution profile as compared to PVP 44,000. Improvement in saturation solubility of the drug in the solid dispersion systems was noted in all cases. Further, IR spectroscopy indicated drug:carrier interactions in solid state in one case and XRD indicated reduction in the crystallinity of CLF in another. It was concluded that solid-dispersion formulations of Clofazimine can be used to design a solid dosage form of the drug, which would have significant advantages over the currently marketed soft gelatin capsule dosage form.

An investigation into the production of paracetamol solid dispersions in PEG 4000 using hot stage differential interference contrast microscopy

The melting and crystallisation behaviour of paracetamol dispersions in polyethylene glycol (PEG) 4000 has been studied using differential interference contrast microscopy fitted with a hot stage. The effects of thermally cycling physical mixes of the two components have been studied with particular reference to the effects of the presence of molten PEG 4000 on the melting behaviour of the model drug. The effects of the drug particle size, the maximum temperature of heating and the holding time at the maximum temperature on the solid dispersion structure have been investigated, with profound changes in structure being observed depending on the manufacturing protocol used. In particular, higher maximum temperatures and holding times with lower drug particle sizes promoted greater dissolution of the drug into the molten PEG. In the majority of systems observed, the remaining paracetamol particles simply persisted as the system was cooled. However, for certain systems, involving high drug loadings and extended holding times and temperatures in the liquid state, the drug recrystallised over a 24-h period to form a fine dispersion within the carrier. The study has therefore demonstrated the usefulness of hot stage microscopy as a method of directly observing the processes involved during the manufacture of solid dispersions and has also indicated that changing the manufacturing protocol may have a profound effect on the structure of the dispersion.

An Investigation into the Melting Behavior of Binary Mixes and Solid Dispersions of Paracetamol and PEG 4000

The melting behavior of paracetamol and polyethylene glycol (PEG) 4000, both individually and as binary systems, has been studied using differential scanning calorimetry. The appearance of the PEG peaks was shown to be highly dependent on scanning rate, with evidence for the existence of once-folded and extended chain forms being noted at slower scanning speeds. The melting peak of paracetamol was found to be profoundly influenced by the presence of the PEG 4000; when observed at all, the endotherm became broader and occurred at a lower temperature on mixing with the polymer. The thermal behavior of the binary mixes was again highly dependent on scanning rate, with faster rates leading to the appearance of the paracetamol peak at lower concentrations. The mixes were then thermally cycled to mimic production of solid dispersions, showing that the temperature cycling of the PEG 4000 could result in binary melting with the paracetamol peak disappearing. The interpretation of these results in terms of the characterization of PEG solid dispersions is discussed

Carbamazepine and Polyethylene Glycol Solid Dispersions: Preparation, in Vitro Dissolution, and Characterization

The objective of this study was to prepare solid dispersions of carbamazepine (CBZ) using polyethylene glycol (PEG) 4000 and PEG 6000, measure the dissolution, and characterize using x-ray diffraction, DSC, and IR spectroscopy. Solid dispersions were prepared by either the melt or solvent methods. A comparison of dissolution profiles of the solid dispersions indicated dramatic increases in the rate and extent of CBZ dissolution from solid dispersions. The dissolution of physical mixtures provided evidence of the solubilizing effects of PEGs. Untreated CBZ exhibited 10.09 ± 2.92% dissolution in 10 min (Dl0); whereas, a melt of PEG 6000 and CBZ at a ratio of 6: 1 provided 36.49 ± 1.97% and a melt of PEG 4000 and CBZ at a ratio of 6: 1 gave a D10 of 23.59 ± 1.45%. The rate and extent of dissolution of CBZ were significantly higher when blends of the PEGs were employed to prepare solid dispersion. The melt method provided significantly higher rate and extent of dissolution of CBZ than the solvent method. Also, the rate and extent of dissolution of CBZ were significantly greater when the solid dispersion was cooled at room temperature as opposed to with ice (faster). X-ray diffractometry revealed almost a complete loss of crystallinity of CBZ in solid dispersions. IR spectrometry indicated an increase in amorphocity of the PEGs after melting. IR spectra suggested that no complexation occurred between the PEGs and CBZ. Alterations in the crystallinity of the system were also supported by the DSC thermograms. Decreasing heats of fusion implied decrease in crystallinity, which would be expected to provide greater dissolution rates. Peak melting temperatures obtained from the thermograms ruled out the possibility of the formation of a eutectic mixture. However, the formation of solid solution could also be a possible mechanism for the increase in dissolution.

Characterization of Glyburide-Polyethylene Glycol Solid Dispersions

AbstractGlyburide (GLY) is an oral hypoglycemic agent that is poorly water soluble. Solid dispersions of polyethylene glycol (PEG) 4000, PEG 6000, and mixtures of PEG 4000 and 6000, were prepared by the melt-and-solvent method. Phase analysis was performed by x-ray powder diffraction and differential scanning calorimetry (DSC) to study the nature of interaction in the solid state. The x-ray diffraction pattern indicated that the dispersion had an amorphous nature as compared to the crystalline drug. The melting endothermal point of GLY was eliminated in the dispersions of DSC thermograms. The results showed that there was no chemical interaction between the drug and the polymer. Also, formation of solid solution is apparent from the DSC thermograms.

Effect of counterions on the interactions in solid dispersions between polyethylene glycol, griseofulvin and alkali dodecyl sulphates

Solid dispersions of polyethylene glycol (PEG) 3000 and 10% w/w griseofulvin with or without different surfactants incorporated were prepared by the melting method. The anionic surfactants lithium dodecyl sulphate (LiDS), sodium dodecyl sulphate (SDS) and potassium dodecyl sulphate (KDS) were added in equivalent amounts, ~ 2% w/w. Phase analysis was performed by X-ray powder diffraction and investigation of short-range structure by 13C-CP/MAS solid-state NMR. In all samples with surfactant added, solid solutions (PEG/MDS) 1− x griseofulvin x were formed. The properties of the solid solutions with Na + and K + ions were almost identical. The addition of LiDS created a structure of the solid solution that was more crystalline than that structure of the sodium- and potassium-containing compounds. The ion with the highest charge-to-radius ratio, Li +, formed chemical bonds that were different from those of the other ions. This was indicated by a changed influence on the hydrophilic parts of the griseofulvin molecules in the lithium compound. The melting behaviour of the solid solutions, investigated by DSC, showed a second transformation in the melt at 186–196°C, indicating a two-phase region in the liquid phase. For the lithium-containing compounds the transformation appeared at lower temperature than for the sodium- and potassium-containing compounds.

Dissolution kinetics of piroxicam in solid dispersions with polyethylene glycol 4000

Solid dispersions were used to increase the solubility of active ingredients, with the ultimate goal of optimizing their bioavailability when incorporated into pharmaceuticals. The studies described were designed to improve the dissolution kinetics of piroxicam by using solid dispersions in polyethylene glycol 4000 and investigating the pharmaceutical availability of the solid dispersions in powdered form and in rigid gelatin capsules. Solid dispersions (melting-solvent method) and physical mixtures were prepared at drug: carrier proportions ranging from 10:90 to 80:20; gelatin capsules were also prepared in our laboratory. The dissolution assay was performed in artificial gastric juice without pepsin at 37°C. The results showed that PEG 4000 increased the amount of piroxicam dissolved in both physical mixtures and solid dispersions. The percentage of the drug dissolved after 5 min was 47.84% for powdered piroxicam, whereas the amount available in solid dispersions reached 83.33 to 96.54% of the drug in solution. The t 75% of powdered piroxicam (19.9 min) decreased to 0.3−2.5 min when PEG was included in a solid dispersion. Preparation of the solid dispersion in capsule form increased the dissolution f 75% from 2.6 to 8.9 min. We conclude that formulations of piroxicam in solid dispersions improve the availability of the drug, both in powdered form and in capsules, the most efficient release occurring at a proportion of drug to polyethylene glycol 4000 of 30:70.

Structures formed by interactions in solid dispersions of the system polyethylene glycol-griseofulvin with charged and non charged surfactants added

Solid dispersions of polyethylene glycol (PEG) 3000 and 10% w/w griseofulvin with incorporation of different types of surfactants were prepared by the melting method. The anionic surfactant sodium dodecyl sulphate (SDS), the cationic surfactant dodecyltrimethylammonium bromide (DTAB) and the nonionic surfactant polyoxyethylene dodecyl ether (Brij) were added in equivalent amounts. Phase analysis was made by X-ray powder diffraction and investigation of the short-range structure by 13C-CP/MAS solid-state NMR. The addition of the different types of surfactants influences the structure of the dispersions in a varying manner. The anionic surfactant SDS forms a solid solution, the nonionic Brij does not influence the particulate dispersion and the cationic DTAB creates a dispersion, that only to a certain extent is a solid solution. The extent of interaction between polymer and surfactant aggregates (micelles) seems to be crucial for the formation of solid solutions of griseofulvin in the polymer phase. The charged surfactants can interact with the polymer forming aggregates, while the nonionic ones show no interaction. When a solid solution is formed, the hydrophilic parts of the griseofulvin molecule are significantly influenced. The surfactant aggregates bind griseofulvin in a molecular form at the surface or, more probably, in the interior of the aggregate.

Dissolution and absorption of nifedipine in polyethylene glycol solid dispersion containing phosphatidylcholine

The in vitro dissolution and in vivo absorption of solid dispersions of nifedipine-polyethylene glycol (nifedipine-PEG) and nifedipine-phosphatidylcholine-polyethylene glycol (nifedipine-PC-PEG) were investigated. The X-ray diffraction patterns and DSC thermograms showed that up to a ratio of 5:95 of nifedipine-PEG, the nifedipine was dispersed homogeneously in an amorphous state or dissolved in the solid dispersions. The incorporation of 5% PC into the nifedipine-PEG solid dispersion demonstrated no change in the solid-state characteristics of nifedipine as in the nifedipine-PEG solid dispersion. The dissolution of nifedipine from the solid dispersions was markedly enhanced as compared with the pure drug. The incorporation of PC into the nifedipine-PEG solid dispersion resulted in a 2.6- and 2.2-fold increase in nifedipine initial dissolution rate and dissolution after 60 min, respectively. This was attributed to the formation of lipid vesicles which entrapped a certain concentration of nifedipine during dissolution. The area under the curve after oral administration of the nifedipine-PC-PEG solid dispersion was 3.4-fold greater than that of the nifedipine-PEG solid dispersion.

Structure of solid dispersions in the system polyethylene glycol-griseofulvin with additions of sodium dodecyl sulphate

Solid dispersions of polyethylene glycol (PEG) 3000 and 10% w/w griseofulvin were prepared by the melting method. Samples were also prepared with 10% w/w of the anionic surfactant sodium dodecyl sulphate (SDS) added to the melt. Phase analysis was performed by X-ray powder diffraction and investigation of the short-range structure by 13C-CP/MAS solid-state NMR. In the samples without the added surfactant, a solid particulate dispersion of griseofulvin in PEG is obtained. The periodic structure of the pure phases is retained and so is the local structure as seen by NMR. When a surfactant is added to the dispersion a solid molecular dispersion i.e., a solid solution, is formed. The interaction between the environment and certain carbons in griseofulvin and SDS is evident. Both hydrophilic and hydrophobic parts of the molecules are influenced in a significant way. The solid solution of griseofulvin in PEG obtained on addition of SDS seems to depend on an interaction between the polymer and SDS in aggregates (micelles). These aggregates can bind griseofulvin in a molecular form at the surface or in the interior of the aggregate.

An investigation into the mechanisms of dissolution of alkyl p-aminobenzoates from polyethylene glycol solid dispersions

The solubility, melting and dissolution behaviour of methyl, ethyl, propyl and butyl p-aminobenzoates (PABAs) have been studied, both alone and as dispersions in polyethylene glycol (PEG) 6000 prepared by the fusion method. The aqueous solubility was found to decrease logarithmically with molecular weight of the PABAs, while a linear increase was found between solubility and initial dissolution rate. The phase diagrams of physical mixtures of the PABAs and PEG 6000 were monotectic in nature, while evidence was found for eutectic formation when the samples were prepared as dispersions. A linear relationship was found between the initial dissolution rate of the dispersions and the aqueous solubility of the PABAs, with the 10% w/w dispersions showing the fastest dissolution rates and the 20% w/w and 50% w/w dispersions and pure PABAs yielding similar results. A model has been proposed whereby at low concentrations within the dispersion the drug is considered to be released into the medium as individual particles, with dissolution occurring over a large surface area, while at higher drug levels, the drug forms a continuous diffusion layer over the dissolving surface.

The dissolution of nortriptyline HCl from polyethylene glycol solid dispersions

The dissolution characteristics of nortriptyline hydrochloride dispersions in a range of different molecular weight polyethylene glycol carriers have been investigated. The release rate was found to be higher from dispersions in PEG 3400 than from the drug alone, while a logarithmic decrease was seen with increasing carrier molecular weight. Studies indicated that there was little difference in release rate from flash- and slow-cooled dispersions. A linear relationship was found between drug dissolution rate and concentration in PEG 20 000 up to 25% w/w drug. The release rate was shown to increase with rotation speed, although the results obtained were not consistent with the relationship proposed by Levich (Levich, V.G., Physicochemical Hydrodynamics, Prentice Hall, NJ, 1962, pp. 60–72). A hypothesis has been presented for the involvement of solubilisation of the drug at the solid-liquid interface as a mechanism for the observed dissolution behaviour.