Controlled Crystallization of the Lipophilic Drug Fenofibrate During Freeze-Drying: Elucidation of the Mechanism by In-Line Raman Spectroscopy

Waard, Hans de; Beer, Thomas De; Hinrichs, Wouter L. J.; Vervaet, Chris; Remon, Jean‐Paul; Frijlink, Henderik W.

doi:10.1208/s12248-010-9215-z

Cited by 36 publications

(17 citation statements)

References 27 publications

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“…1. The vast majority of literature dealing with this compound concerns its clinical action, bioavailability, and formulation [1][2][3][4][5]. In addition there is some limited literature concerning its physico-chemical properties [6][7][8][9][10][11], including spectroscopic and analytical data [12][13][14][15], and the crystal structures of its two known polymorphs [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Thermodynamics of fenofibrate and solubility in pure organic solvents

Watterson

Hudson

Svärd

et al. 2014

Fluid Phase Equilibria

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Highlights! ! Solubility data of fenofibrate FI was collected between 5-45°C in seven pure solvents.! ! Melting data and heat capacity of the solid and the melt were measured with DSC.! ! Fusion thermodynamics and ideal solubility were calculated using experimental data.! ! The heat capacity component of the enthalpy of fusion is shown to be important.! ! In some solvents the activity coefficient term controls the shape of van't Hoff plots. AbstractCalorimetric data on the melting of 1-methylethyl 2-[4-(4-chlorobenzoyl)-phenoxy]-2-methylpropanoate (fenofibrate) and the heat capacity of the solid and the melt have been determined, from which the Gibbs energy, enthalpy and entropy of fusion are calculated. Solid-liquid solubility data have been collected by a gravimetric method in seven pure solvents (methanol, ethanol, 1-propanol, 2-propanol, ethyl acetate, acetonitrile, and acetone) across a range of temperatures. Fenofibrate is much more soluble in ethyl acetate, acetonitrile and acetone compared to alcohols. In the alcohols the solubility increases with aliphatic chain length. The Gibbs energy of fusion is used to estimate the activity of the solid within a Raoult's law framework. Except for ethyl acetate solutions which are almost ideal, solutions in all evaluated solvents exhibit positive deviation from Raoult's law, and in the alcohols the activity coefficient ranges up to 25. It is shown that the heat capacity component of the enthalpy of fusion is not negligible at room temperature, in spite of the proximity to the melting point, and furthermore that the temperature dependence of the activity coefficient in the saturated solution has a governing influence on the van't Hoff enthalpy of solution in acetonitrile and the alcohols. Crystals obtained by two different methods from a range of solvents have been analysed by PXRD, FTIR and NMR spectroscopy, TGA and DSC, and have in all cases been shown to consist of the stable polymorph (form I).

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Section: Introductionmentioning

confidence: 99%

“…Heat capacity difference (melt -solid) k 1 Heat capacity regression coefficient k 2 Heat capacity regression coefficient A c c e p t e d M a n u s c r i p t…”

mentioning

confidence: 99%

Thermodynamics of fenofibrate and solubility in pure organic solvents

Watterson

Hudson

Svärd

et al. 2014

Fluid Phase Equilibria

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“…This dispersion was subsequently homogenized in Few carriers that can help in increasing the oral bioavailability of PPD are available; 13 therefore, a novel carrier that can simultaneously improve dissolution and permeation is required. Colloidal dispersions of bicontinuous cubic phases formed in a monoolein/poloxamer/water system have been proposed as potential drug carriers 14,15 because (1) they are bioadhesive, (2) present a permeation enhancer as the structure-forming lipid (glyceryl monooleate), and (3) have the ability to incorporate compounds independent of their solubility and sustain their delivery. [16][17][18] The emulsification of cubic lipid phases in water results in the formation of cubosomes and can be defined as a nanoparticle dispersion system.…”

Section: Preparation Of Gmo-based Dispersions By Fragmentationmentioning

confidence: 99%

Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies

Jin¹,

Zhang²,

Sun³

et al. 2013

IJN

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Background: 20(S)-protopanaxadiol (PPD), similar to several other anticancer agents, has low oral absorption and is extensively metabolized. These factors limit the use of PPD for treatment of human diseases. Methods: In this study, we used cubic nanoparticles containing piperine to improve the oral bioavailability of PPD and to enhance its absorption and inhibit its metabolism. Cubic nanoparticles loaded with PPD and piperine were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel and verified using transmission electron microscopy and differential scanning calorimetry. We evaluated the in vitro release of PPD from these nanoparticles and its absorption across the Caco-2 cell monolayer model, and subsequently, we examined the bioavailability and metabolism of PPD and its nanoparticles in vivo. Results: The in vitro release of PPD from these nanoparticles was less than 5% at 12 hours. PPDcubosome and PPD-cubosome loaded with piperine (molar ratio PPD/piperine, 1:3) increased the apical to basolateral permeability values of PPD across the Caco-2 cell monolayer from 53% to 64%, respectively. In addition, the results of a pharmacokinetic study in rats showed that the relative bioavailabilities of PPD-cubosome [area under concentration-time curve (AUC) 0-∞ ] and PPD-cubosome containing piperine (AUC 0-∞ ) compared to that of raw PPD (AUC 0-∞ ) were 166% and 248%, respectively. Conclusion: The increased bioavailability of PPD-cubosome loaded with piperine is due to an increase in absorption and inhibition of metabolism of PPD by cubic nanoparticles containing piperine rather than because of improved release of PPD. The cubic nanoparticles containing piperine may be a promising oral carrier for anticancer drugs with poor oral absorption and that undergo extensive metabolism by cytochrome P450.

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“…Nanocrystals may be able to reduce the dose to be administered, provide a sustained drug release and increase patient compliance 7 .…”

Section: Introductionmentioning

confidence: 99%

Untitled

2018

IJPSR

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ABSTRACT:Poor aqueous solubility is the main problem in development of effective formulation which affects stability and bioavailability of drug formulation. So there is need of systematic formulation approach to make such poorly soluble drugs bioavailable. In the present investigation attempt has been made to investigate the effect of soluplus on solubility of gliclazide by preparing its nanocrystals. Nanocrystals of gliclazide with soluplus were prepared by using drug: carrier ratios of 1:0.5, 1:1,

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Controlled Crystallization of the Lipophilic Drug Fenofibrate During Freeze-Drying: Elucidation of the Mechanism by In-Line Raman Spectroscopy

Cited by 36 publications

References 27 publications

Thermodynamics of fenofibrate and solubility in pure organic solvents

Thermodynamics of fenofibrate and solubility in pure organic solvents

Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies

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