Properties of Rapidly Dissolving Eutectic Mixtures of Poly(ethylene glycol) and Fenofibrate:The Eutectic Microstructure

Law, Devalina; Wang, Weili; Schmitt, Eric A.; Qiu, Yihong; Krill, Steven L.; Fort, James J.

doi:10.1002/jps.10324

Cited by 113 publications

(85 citation statements)

References 23 publications

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“…8 We use fenofibrate as a hydrophobic model drug; amorphous fenofibrate is an undercooled liquid at room temperature since it has a glass transition temperature, T g , of À20 1C 7 and a melting temperature, T m , of 80 1C. 11 We dissolve fenofibrate in ethanol at 5 mg ml À1 , and inject the solution through one liquid inlet at 1 ml h À1 using syringe pumps; we block the second liquid inlet to avoid leakage of the liquid and the air. We introduce air by applying 0.28 MPa to all the air inlets and collect the spray dried undercooled liquid drops 15 cm apart from the nozzle on a flat substrate.…”

Section: Resultsmentioning

confidence: 99%

Crystallization of undercooled liquid fenofibrate

Amstad

Spaepen

Weitz

2015

Phys. Chem. Chem. Phys.

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Formulation of hydrophobic drugs as amorphous materials is highly advantageous as this increases their solubility in water and therefore their bioavailability. However, many drugs have a high propensity to crystallize during production and storage, limiting the usefulness of amorphous drugs. We study the crystallization of undercooled liquid fenofibrate, a model hydrophobic drug. Nucleation is the ratelimiting step; once seeded with a fenofibrate crystal, the crystal rapidly grows by consuming the undercooled liquid fenofibrate. Crystal growth is limited by the incorporation of molecules into its surface. As nucleation and growth both entail incorporation of molecules into the surface, this process likely also limits the formation of nuclei and thus the crystallization of undercooled liquid fenofibrate, contributing to the good stability of undercooled liquid fenofibrate against crystallization.

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Section: Resultsmentioning

confidence: 99%

Crystallization of undercooled liquid fenofibrate

Amstad

Spaepen

Weitz

2015

Phys. Chem. Chem. Phys.

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“…It is used to treat hypercholesterolemia, heart disease, and diabetic complications [2]. The compound is practically insoluble in water (0.1 lg mL -1 ), which limits its absorption from the gastrointestinal tract [3]. Several methods have been employed to improve the solubility of FEN, including micronization [4][5][6], preparation of solid dispersions [7,8], preparation of eutectic mixtures with polymers [3], formulation of nanosuspension [5], self-microemulsifying drug delivery systems [9], and an inclusion complex with b-cyclodextrin [10], the addition of surfactants, such as sodium lauryl sulphate, [11], the formulation of the drug into granules using slugging and liquisolid compaction techniques [12], or the melt granulation technique [13,14].…”

Section: Introductionmentioning

confidence: 99%

Dissolution study and thermal analysis of fenofibrate–Pluronic F127 solid dispersions

Karolewicz

Gajda

Pluta

et al. 2015

J Therm Anal Calorim

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Prepared solid dispersions were applied to a drug with low water solubility to improve its dissolution rate. Fenofibrate (FEN) is a Biopharmaceutical Classification System (BCS) class-II (poorly water-soluble) drug, and its bioavailability is limited by the dissolution rate. The physical state of FEN in solid dispersions with Pluronic F127 (PLU) prepared using the fusion method was assessed using Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). The DSC investigation revealed that FEN and PLU form a simple eutectic system. The DSC, XRPD, and FTIR studies of the investigated solid dispersions revealed no interaction between FEN and PLU. The intrinsic dissolution rate (IDR) of FEN from solid dispersions was significantly increased compared with the pure drug. The enhancement in the intrinsic dissolution rate was approximately 134-fold for solid dispersions containing 30/70 % w/w of FEN/PLU.

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“…Poor water solubility and slow dissolution are often the main reasons for the rejection of potentially active drugs [10,11]. Several approaches have been employed to overcome this problem, such as the preparation of solid dispersions of an active agent in a biologically inert matrix [12][13][14], drug dissolution in the presence of polymeric micelles in the dissolution medium [15], addition of surfactants [15][16][17][18], micronization-particle size reduction to nano-or microsize [19][20][21], melt granulation technique [22,23] and formation of eutectics [24,25], including drug-polymer component systems [26,27].…”

Section: Introductionmentioning

confidence: 99%

Phase diagram and dissolution studies of the fenofibrate–acetylsalicylic acid system

Gòrniak

Wojakowska

Karolewicz

et al. 2010

J Therm Anal Calorim

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Enhancement of the dissolution rate of poorly soluble compounds through the formation of drug-drug eutectics was investigated using fenofibrate and acetylsalicylic acid. Solid-liquid equilibria in the system under study were investigated by differential scanning calorimetry (DSC). The phase diagram for the whole range of compositions was constructed. In addition, existence of a metastable polymorph of fenofibrate has been confirmed. The investigation has revealed that acetylsalicylic acid and fenofibrate form a simple eutectic mixture containing 0.958 mol fraction of fenofibrate at the eutectic point. Dissolution rate improvement of fenofibrate correlated with the phase diagram. The amount of fenofibrate released from the solid dispersions that contained fenofibrate as the eutectic mixture with acetylsalicylic acid was at least threefold higher compared to untreated fenofibrate.

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Properties of Rapidly Dissolving Eutectic Mixtures of Poly(ethylene glycol) and Fenofibrate:The Eutectic Microstructure

Cited by 113 publications

References 23 publications

Crystallization of undercooled liquid fenofibrate

Crystallization of undercooled liquid fenofibrate

Dissolution study and thermal analysis of fenofibrate–Pluronic F127 solid dispersions

Phase diagram and dissolution studies of the fenofibrate–acetylsalicylic acid system

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