References of "International Journal of Pharmaceutics"
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See detailMicrocrystalline cellulose, a direct compression binder in a quality by design environment—A review
Thoorens, Grégory; Krier, Fabrice ULg; Leclercq, Bruno et al

in International Journal of Pharmaceutics (2014), 473(1-2), 64-72

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See detailCharacterization and optimization of GMO-based gels with long term release for intraarticular administration
Réeff, J.; Gaignaux, A.; Goole, J. et al

in International Journal of Pharmaceutics (2013), 451(1-2), 95-103

Osteoarthritis is characterized by slow degenerative processes in the articular cartilage within synovial joints. It could be interesting to develop a sustained-release formulation that could be effective ... [more ▼]

Osteoarthritis is characterized by slow degenerative processes in the articular cartilage within synovial joints. It could be interesting to develop a sustained-release formulation that could be effective on both pain/inflammation and restoration of mechanical integrity of the joint. Recently, an injectable system based on glycerol monooleate (GMO), containing clonidine as a model hydrophilic analgesic/anti-inflammatory drug and hyaluronic acid as a viscoelastic scaffold, showed promising potential as a biodegradable and biocompatible preparation to sustain the drug activity. However, drug release from the system is relatively fast (complete within 1 week) and the underlying drug release mechanisms not fully understood. The aims of this study were: (i) to significantly improve this type of local controlled drug delivery system by further sustaining clonidine release, and (ii) to elucidate the underlying mass transport mechanisms. The addition of FDA-approved inactive ingredients such as sodium oleate or purified soybean oil was found to be highly effective. The release rate could be substantially reduced (e.g., 50% release after 10 days), due to the increased hydrophobicity of the systems, resulting in slower and reduced water uptake and reduced drug mobility. Interestingly, Fick's second law of diffusion could be used to quantitatively describe drug release. [less ▲]

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See detailDual anticancer drug/superparamagnetic iron oxide-loaded PLGA-based nanoparticles for cancer therapy and magnetic resonance imaging
Schleich, N.; Sibret, Pierre ULg; Danhier, P. et al

in International Journal of Pharmaceutics (2013), 447(1-2), 94-101

We developed dual paclitaxel (PTX)/superparamagnetic iron oxide (SPIO)-loaded PLGA-based nanoparticles for a theranostic purpose. Nanoparticles presented a spherical morphology and a size of 240 nm. The ... [more ▼]

We developed dual paclitaxel (PTX)/superparamagnetic iron oxide (SPIO)-loaded PLGA-based nanoparticles for a theranostic purpose. Nanoparticles presented a spherical morphology and a size of 240 nm. The PTX and iron loading were 1.84 ± 0.4 and 10.4 ± 1.93 mg/100 mg respectively. Relaxometry studies and phantom MRI demonstrated their efficacy as T2 contrast agent. Significant cellular uptake by CT26 cells of nanoparticles was shown by Prussian blue staining and fluorescent microscopy. While SPIO did not show any toxicity in CT-26 cells, PTX-loaded nanoparticles had a cytotoxic activity. PTX-loaded nanoparticle (5 mg/kg) with or without co-encapulated SPIO induced in vivo a regrowth delay of CT26 tumors. Together these multifunctional nanoparticles may be considered as future nanomedicine for simultaneous molecular imaging, drug delivery and real-time monitoring of therapeutic response. [less ▲]

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See detailDrug delivery to inflamed colon by nanoparticles: comparison of different strategies
Coco, Régis; Plapied, Laurence; Pourcelle, Vincent et al

in International Journal of Pharmaceutics (2013), 440(1), 3-12

For inflammatory bowel disease (IBD) treatment, local delivery of molecules loaded in nanoparticles to the inflamed colon could be a promising strategy. The aim of this study was to investigate how drug ... [more ▼]

For inflammatory bowel disease (IBD) treatment, local delivery of molecules loaded in nanoparticles to the inflamed colon could be a promising strategy. The aim of this study was to investigate how drug-loaded polymeric nanoparticles target the site of inflammation and to analyse the influence of different colon-specific delivery strategies. Three different polymeric nanoparticles were formulated using ovalbumin (OVA) as a model drug. pH-sensitive nanoparticles were made with Eudragit® S100. Mucoadhesive nanoparticles were created with trimethylchitosan (TMC). A mix of polymers, PLGA, PEG-PLGA and PEG-PCL, were used to obtain a sustained drug delivery. Furthermore, ligands targeting immune cells (i.e. mannose) or the inflamed colon (i.e. a specific peptide) were grafted on the PEG chain of PCL. Interaction of nanoparticles with the intestinal epithelium was explored using Caco-2 monolayers designed to mimic an inflamed epithelium and then visualized using confocal laser microscopy. TMC nanoparticles had the highest apparent permeability for OVA in the untreated model. However, in the inflamed model, there were no difference between TMC, PLGA-based and Eudragit® nanoparticles. The uptake of nanoparticles in the inflamed mouse colon was assessed in a horizontal diffusion chamber. Mannose-grafted PLGA nanoparticles showed the highest accumulation of OVA in inflamed colon. Based on these results, active targeting of macrophages and dendritic cells may be a promising approach for targeting the colon in IBD. [less ▲]

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See detailPAT tools for the control of co-extrusion implants manufacturing process
Krier, Fabrice ULg; Mantanus, Jérome; Sacre, Pierre-Yves ULg et al

in International Journal of Pharmaceutics (2013), 458

Hot melt extrusion is a novel pharmaceutical manufacturing process technique. In this study, we identified four Critical Quality Attributes (CQAs) of the implant manufacturing process by hot melt ... [more ▼]

Hot melt extrusion is a novel pharmaceutical manufacturing process technique. In this study, we identified four Critical Quality Attributes (CQAs) of the implant manufacturing process by hot melt extrusion: the implant diameter, the quantity of the Active Pharmaceutical Ingredient (API), the homogeneity distribution of API and the thickness of the membrane. We controlled the implant diameter and the quantity of API in-line with a laser measurement, NIR and Raman spectroscopy, respectively. These two different spectroscopic techniques provided comparable results. In fact, the RMSEC and RMSECV were very close in each PAT technique but NIR spectroscopy was easier to use and less sensitive to external changes. For the control of the homogeneity of API distribution and the thickness of the membrane, we used successfully Raman spectroscopy imaging. These PAT tools help reducing analysis time. [less ▲]

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See detailTocol modified glycol chitosan for the oral delivery of poorly soluble drugs
Duhem, Nicolas; Rolland, Julien; Riva, Raphaël ULg et al

in International Journal of Pharmaceutics (2012), 423(2), 452-460

The aim of this study was to develop tocol derivatives of chitosan able (i) to self-assemble in the gastrointestinal tract and (ii) to enhance the solubility of poorly soluble drugs. Among the derivatives ... [more ▼]

The aim of this study was to develop tocol derivatives of chitosan able (i) to self-assemble in the gastrointestinal tract and (ii) to enhance the solubility of poorly soluble drugs. Among the derivatives synthesized, tocopherol succinate glycol chitosan (GC-TOS) conjugates spontaneously formed micelles in aqueous solution with a critical micelle concentration of 2 μg mL−1. AFM and TEM analysis showed that spherical micelles were formed. The GC-TOS increased water solubility of 2 model class II drugs. GC-TOS loading efficiency was 2.4% (w/w) for ketoconazole and 0.14% (w/w) for itraconazole, respectively. GC-TOS was non-cytotoxic at concentrations up to 10 mg mL−1. A 3.4-fold increase of the apparent permeation coefficient of ketoconazole across a Caco-2 cell monolayer was demonstrated. Tocol polymer conjugates may be promising vehicles for the oral delivery of poorly soluble drugs. [less ▲]

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See detailLiposome surface charge influence on skin penetration behaviour
Gillet, Aline ULg; Compère, Philippe ULg; Lecomte, Frédéric ULg et al

in International Journal of Pharmaceutics (2011), 411(1-2), 223-231

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See detailNuclear delivery of a therapeutic peptide by long circulating pH-sensitive liposomes: Benefits over classical vesicles.
Ducat, Emilie ULg; Deprez, Julie ULg; Gillet, Aline ULg et al

in International Journal of Pharmaceutics (2011)

The purpose of this study is to propose a suitable vector combining increased circulation lifetime and intracellular delivery capacities for a therapeutic peptide. Long circulating classical liposomes ... [more ▼]

The purpose of this study is to propose a suitable vector combining increased circulation lifetime and intracellular delivery capacities for a therapeutic peptide. Long circulating classical liposomes [SPC:CHOL:PEG-750-DSPE (47:47:6 molar% ratio)] or pH-sensitive stealth liposomes [DOPE:CHEMS:CHOL:PEG(750)-DSPE (43:21:30:6 molar% ratio)] were used to deliver a therapeutic peptide to its nuclear site of action. The benefit of using stealth pH-sensitive liposomes was investigated and formulations were compared to classical liposomes in terms of size, shape, charge, encapsulation efficiency, stability and, most importantly, in terms of cellular uptake. Confocal microscopy and flow cytometry were used to evaluate the intracellular fate of liposomes themselves and of their hydrophilic encapsulated material. Cellular uptake of peptide-loaded liposomes was also investigated in three cell lines: Hs578t human epithelial cells from breast carcinoma, MDA-MB-231 human breast carcinoma cells and WI-26 human diploid lung fibroblast cells. The difference between formulations in terms of peptide delivery from the endosome to the cytoplasm and even to the nucleus was investigated as a function of time. Characterization studies showed that both formulations possess acceptable size, shape and encapsulation efficiency but cellular uptake studies showed the important benefit of the pH-sensitive formulation over the classical one, in spite of liposome PEGylation. Indeed, stealth pH-sensitive liposomes were able to deliver hydrophilic materials strongly to the cytoplasm. Most importantly, when encapsulated in pH-sensitive stealth liposomes, the peptide was able to reach the nucleus of tumorigenic and non tumorigenic breast cancer cells. [less ▲]

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See detailIn vitro identification of targeting ligands of human M cells by phage display
Fievez, V.; Plapied, L.; Plaideau, C. et al

in International Journal of Pharmaceutics (2010), 394(1-2), 35-42

To improve transport of vaccine-loaded nanoparticles, the phage display technology was used to identify novel lead peptides targeting human M cells. Using an in vitro model of the human follicle ... [more ▼]

To improve transport of vaccine-loaded nanoparticles, the phage display technology was used to identify novel lead peptides targeting human M cells. Using an in vitro model of the human follicle-associated epithelium (FAE) which contains both Caco-2 and M cells, a T7 phage display library was screened for its ability either to bind the apical cell surface of or to undergo transcytosis across Caco-2 cells or FAE. The selection for transcytosis across both enterocytes and FAE identified three different peptide sequences (CTGKSC, PAVLG and LRVG) with high frequency. CTGKSC and LRVG sequences enhanced phage transport across M-like cells. When polymeric nanoparticles were grafted with the sequences CTGKSC and LRVG, their transport by FAE was significantly enhanced. These peptides could therefore be used to enhance the transport of vaccine-loaded nanoparticles across the intestinal mucosal barrier. [less ▲]

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See detailDevelopment of a new topical system: Drug-in-cyclodextrin-in-deformable liposome
Gillet, Aline ULg; Grammenos, Angeliki ULg; Compère, Philippe ULg et al

in International Journal of Pharmaceutics (2009), 380(1-2), 174-180

A new delivery system for cutaneous administration combining the advantages of cyclodextrin inclusion complexes and those of deformable liposomes was developed, leading to a new concept: drug ... [more ▼]

A new delivery system for cutaneous administration combining the advantages of cyclodextrin inclusion complexes and those of deformable liposomes was developed, leading to a new concept: drug-incyclodextrin-in-deformable liposomes. Deformable liposomes made of soybean phosphatidylcholine (PC) or dimyristoylphosphatidylcholine (DMPC) and sodium deoxycholate as edge activator were compared to classical non-deformable liposomes. Liposomes were prepared by the film evaporation method. Betamethasone, chosen as the model drug,was encapsulated in the aqueous cavity of liposomes by the use of cyclodextrins. Cyclodextrins allowan increase in the aqueous solubility of betamethasone and thus, the encapsulation efficiency in liposome vesicles. Liposome size, deformability and encapsulation efficiency were calculated. The best results were obtained with deformable liposomes made of PC in comparison with DMPC. The stability of PC vesicles was evaluated by measuring the leakage of encapsulated calcein on the one hand and the leakage of encapsulated betamethasone on the other hand. In vitro diffusion studies were carried out on Franz type diffusion cells through polycarbonate membranes. In comparison with non-deformable liposomes, these new vesicles showed improved encapsulation efficiency, good stability and higher in vitro diffusion percentages of encapsulated drug. They are therefore promising for future use in ex vivo and in vivo experiments. [less ▲]

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See detailTheoretical and Experimental Vibrational Study of Miconazole and Its Dimers with Organic Acids: Application to the IR Characterization of Its Inclusion Complexes with Cyclodextrins
Barillaro, Valéry; Dive, Georges ULg; Ziemons, Eric ULg et al

in International Journal of Pharmaceutics (2008), 350(1-2), 155-165

The geometry, frequency and intensity of the vibrational bands of miconazole were derived from the density functional theory (DFT) calculations with the hybrid functional B3LYP and the 6-31G(d) basis set ... [more ▼]

The geometry, frequency and intensity of the vibrational bands of miconazole were derived from the density functional theory (DFT) calculations with the hybrid functional B3LYP and the 6-31G(d) basis set. Starting from the fully AM1 optimized geometries of miconazole/betaCD/acids complexes, the miconazole/acid dimers were reoptimized at the B3LYP/6-31G(d) level. Three acids were studied: maleic, fumaric and l-tartaric acids. To begin with the vibrational spectral data obtained from solid phase in mid FT-IR spectrum of miconazole and its dimers are assigned based on the results of the normal modes calculations. All the observed spectra and the calculated ones are found to be in good agreement. In a second step, theoretical results allowed the assignment of FT-IR spectrum for the miconazole/HPgammaCD inclusion complex produced by supercritical carbon dioxide treatment and confirmed the inclusion of miconazole. The experimental spectra for the miconazole/HPgammaCD/acids complexes prepared by supercritical carbon dioxide processing were also assigned using theoretical results. The results confirmed the presence of a genuine inclusion complex and also the interaction between miconazole and the acid. [less ▲]

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See detailTheoretical and Experimental Investigations of Organic Acids/Cyclodextrin Complexes and Their Consequences Upon the Formation of Miconazole/Cyclodextrin/Acid Ternary Inclusion Complexes
Barillaro, Valéry; Dive, Georges ULg; Bertholet, Pascal et al

in International Journal of Pharmaceutics (2008), 347(1-2), 62-70

(1)H NMR spectrometry, FT-IR spectroscopy, as well as molecular modeling at the AM1 level and normal mode analysis were used to characterise the interactions and the formation of inclusion complexes ... [more ▼]

(1)H NMR spectrometry, FT-IR spectroscopy, as well as molecular modeling at the AM1 level and normal mode analysis were used to characterise the interactions and the formation of inclusion complexes between three organic acids: maleic, fumaric, L-tartaric acids and betaCD. In aqueous medium, the complexation was confirmed by (1)H NMR spectroscopy using two-dimensional technique. The stable geometries of the complexes were determined by molecular modeling. Experimental infrared frequencies were assigned on the base of the vibrational normal mode calculation at the fully optimized geometry for the inclusion complexes. All the results point out the presence of stable inclusion complexes between acids and betaCD at the solid state. These results show the double role of the acid. Correlated with the theoretical and experimental data previously obtained for the miconazole/CD/acids complexes, in function of both acids and CDs structures, the acids can either stabilize the complexes by formation of a multicomponent complex or form acid/CD inclusion complexes, hindering the guest inclusion. [less ▲]

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See detailPEGylated quaternized copolymer/DNA complexes for gene delivery
Vroman, Benoît; Ferreira, Isabel; Jérôme, Christine ULg et al

in International Journal of Pharmaceutics (2007), 344(1-2), 88-95

The aim of this study was to improve the colloidal stability, decrease unspecific interactions with cells and blood components of a novel gene delivery system composed of epsilon-caprolactone and ... [more ▼]

The aim of this study was to improve the colloidal stability, decrease unspecific interactions with cells and blood components of a novel gene delivery system composed of epsilon-caprolactone and quaternized epsilon-caprolactone. For this purpose, diblock 50/50 copolymer was used to generate complexes-with DNA by either the solvent evaporation technique and by dialysis. The size, surface charge and degree of interaction of the plasmid-loaded formulations were measured. Then, polyplexes were combined with a poly(CL)-b-PEG copolymer to create a hydrophilic corona on the surface of the complexes. The cytotoxicity, transfection efficiency and cellular uptake of polyplexes and their association with PEG were evaluated on HeLa cells. The dialysis method did not allow to reduce the size of complexes as compared to the solvent evaporation method. The zeta potential of polyplexes became positive from a charge ratio of 4. The degree of interaction of copolymer with plasmid DNA was very high. Cytotoxicity and transfection efficiency were found to be comparable to polyethylenimine 50 kDa. Association of polyplexes with poly(CL)-b-PEG copolymer led to a small increase in particle size and a sharp decrease of charge surface. Cytotoxicity, transfection efficiency and cellular uptake were significantly reduced relative to unshielded copolymer/DNA complexes. The PEGylated formulations may be an attractive approach for an in vivo application. [less ▲]

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See detailStudy of the relationship between lipid binding properties of cyclodextrins and their effect on the integrity of liposomes
Piel, Géraldine ULg; Piette, Marie ULg; Barillaro, Valery et al

in International Journal of Pharmaceutics (2007), 338(1-2), 35-42

It is well known that cyclodextrins are able to extract lipids constituting membranes, increasing their fluidity and permeability. This behaviour towards biological membranes is directly linked to the ... [more ▼]

It is well known that cyclodextrins are able to extract lipids constituting membranes, increasing their fluidity and permeability. This behaviour towards biological membranes is directly linked to the toxicological effects of methylated cyclodextrins. However, confusion is currently made in the literature between the different methylated cyclodextrin derivatives. Moreover, a new methylated cyclodextrin derivative recently occurred in the market. the Crysmeb (R). We wanted to compare and understand the effect of the most currently used cyclodextrins on a model membrane. We studied the influence of natural cyclodextrins (beta CD and gamma CD), methylated derivatives (2,6-dimethyl-beta CD (Dimeb), 2,3,6-trimethyl-beta CD (Trimeb) and randomly methylated-beta CD (Rameb), as well as the new derivative Crysmeb), hydroxypropylated derivatives (HP beta CD of different substitution degrees and HP gamma CD) and the sulfobutylated derivative (SBE beta CD) on the release of a fluorescent marker encapsulated in the inner cavity of liposomes. It was shown that the observed effect on calcein release can be directly related to the affinity of cyclodextrins for both lipid components of liposomes, cholesterol and phosphatidylcholine. From this relationship, we were able to determine, for each cyclodextrin, a theoretical concentration giving rise to 50% or 100% calcein release. This theoretical concentration was confirmed experimentally. We have also showed that cyclodextrins which provoke calcein release also induce large structure modifications of liposomes. (c) 2007 Elsevier B.V. All rights reserved. [less ▲]

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See detailTheoretical and experimental investigations on miconazole/cyclodextrin/acid complexes: Molecular modeling studies
Barillaro, Valéry; Dive, Georges ULg; Bertholet, Pascal et al

in International Journal of Pharmaceutics (2007), 342(1-2), 152-160

The inclusion of miconazole into cyclodextrin cavity has been demonstrated by different authors. Preliminary studies have shown which fragment of the molecule is involved in the inclusion. In the present ... [more ▼]

The inclusion of miconazole into cyclodextrin cavity has been demonstrated by different authors. Preliminary studies have shown which fragment of the molecule is involved in the inclusion. In the present study, AM1 approximate molecular orbital calculations have been performed on several cyclodextrins complexes ( CD, HP CD and HP CD) with miconazole and acidic compounds (maleic, fumaric and L-tartaric acids) as partners. For all the binary complexes, the inclusion of the dichlorobenzene–CH2–O-group leads to the most stable complex. For the ternary complexes, depending on their conformation and/or their structures, the acids can either stabilize or destabilize the complex. All the theoretical results were in good agreement with experimental data of miconazole inclusion yields into cyclodextrins. This work clearly demonstrates that the structure of both cyclodextrin and acid plays a key-role in the formation of inclusion complexes. [less ▲]

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See detailBetamethasone-in-cyclodextrin-in-liposome: The effect of cyclodextrins on encapsulation efficiency and release kinetics
Piel, Géraldine ULg; Piette, Marie ULg; Barillaro, Valery et al

in International Journal of Pharmaceutics (2006), 312(1-2), 75-82

Lipophilic drugs have limited solubility in phospholipid systems, hence maximum entrapment levels in liposomes are known to be low. "Drugs-in-cyclodextrin-in-liposome" systems were previously proposed to ... [more ▼]

Lipophilic drugs have limited solubility in phospholipid systems, hence maximum entrapment levels in liposomes are known to be low. "Drugs-in-cyclodextrin-in-liposome" systems were previously proposed to overcome this drawback but studies were limited to beta CD and HP beta CD. In some cases, other cyclodextrins may be more interesting than beta CD or HPPCD, such as methylated cyclodextrins. However, these cyclodextrins are known to extract lipid components from the lipid membrane, which may destabilize liposomes. We tested the influence of several cyclodextrins (beta CD, gamma CD, Dimeb, Trimeb, Crysmeb, Rameb, HP beta CD and HP gamma CD) on the aqueous solubility of betamethasone by phase solubility diagrams and on the encapsulation efficiency in liposomes. The release kinetics of betamethasone was studied using Franz diffusion cells. We showed that release kinetics are directly correlated with encapsulation efficiency, which is closely related to betamethasone concentration in cyclodextrin complex solution. No liposome destruction was observed, even with the testing of methylated cyclodextrins at the highest concentration (40 mM). This can be explained by the fact that these cyclodextrins have a higher affinity for betamethasone than for cholesterol. This was proved by the comparison of phase solubility diagrams of both betamethasone and cholesterol. (c) 2006 Elsevier B.V. All rights reserved. [less ▲]

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See detailSystematic characterization of oil-in-water emulsions for formulation design
Roland, Isabelle ULg; Piel, Géraldine ULg; Delattre, Luc ULg et al

in International Journal of Pharmaceutics (2003), 263(1-2), 85-94

Oil-in-water emulsions varying in surfactant concentration and manufacturing process were prepared. About 10 experiments were performed to characterize them. The goal of this research was to find Out ... [more ▼]

Oil-in-water emulsions varying in surfactant concentration and manufacturing process were prepared. About 10 experiments were performed to characterize them. The goal of this research was to find Out which tests should systematically be carried Out to assess efficiently the stability and the properties of ail emulsified preparation. Thus, formulation design requires at least the measurement of the droplet size, the determination of the zeta potential, a TurbiScan(R) analysis, the investigation of the stability under centrifugation and freeze/thaw cycles. If the emulsion contains an active substance, stability under storage at 4 degreesC and microscopic analysis are relevant. Quality Control Should be improved by measurements of viscosity and pH. (C) 2003 Elsevier B.V. All rights reserved. [less ▲]

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See detailComparison of the Iv Pharmacokinetics in Sheep of Miconazole-Cyclodextrin Solutions and a Micellar Solution
Piel, Géraldine ULg; Evrard, Brigitte ULg; Van Hees, Thierry ULg et al

in International Journal of Pharmaceutics (1999), 180(1), 41-5

The pharmacokinetics of miconazole were studied after intravenous administration to six sheep (4 mg/kg) of three aqueous solutions: a marketed micellar solution containing polyoxyl-35 castor oil (Daktarin ... [more ▼]

The pharmacokinetics of miconazole were studied after intravenous administration to six sheep (4 mg/kg) of three aqueous solutions: a marketed micellar solution containing polyoxyl-35 castor oil (Daktarin IV(R)) was compared with two solutions both containing 50 mM lactic acid and a cyclodextrin derivative (100 mM HP-betaCD or 50 mM SBE7-betaCD). The aim of this work was to demonstrate that these cyclodextrin derivatives (CDs) have no effect on the pharmacokinetics of miconazole by comparison with the micellar solution. The plasma concentration time curves have shown that there is no significant difference between the three solutions. [less ▲]

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See detailDevelopment of a non-surfactant parenteral formulation of miconazole by the use of cyclodextrins
Piel, Géraldine ULg; Evrard, Brigitte ULg; Fillet, Marianne ULg et al

in International Journal of Pharmaceutics (1998), 169

Miconazole is an antimycotic drug exhibiting a very poor water solubility (B1.03 mg:ml). It has been shown that cyclodextrins (CDs) are able to form inclusion complexes with miconazole and that they are ... [more ▼]

Miconazole is an antimycotic drug exhibiting a very poor water solubility (B1.03 mg:ml). It has been shown that cyclodextrins (CDs) are able to form inclusion complexes with miconazole and that they are able to increase its aqueous solubility. Miconazole is a weak base whose solubility depends of the pH. The purpose of this study was to investigate the influence of both CDs and different acids on the solubility of miconazole. It was found that a synergistic effect existed between CDs and different acids. The combination of hydroxypropyl-bCD (HP-bCD) (100 mM) or sulfobutylether 7-bCD (SBE7-bCD) (50 mM) and lactic acid (50 mM) allowed to dissolve more than 10 mg of miconazole per ml. NMR studies confirmed the formation of an inclusion complex miconazole–CD in an acidic medium. It was also shown by the NMR studies that the complex formed was a 1:1 complex. These results demonstrate that it is possible to develop a parenteral aqueous solution of miconazole without surfactant. [less ▲]

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