Gattefosse SAS

Saint-Pierre-du-Chemin, France

Gattefosse SAS

Saint-Pierre-du-Chemin, France
Time filter
Source Type

N'Goma J.-C.B.,Aix - Marseille University | Amara S.,Aix - Marseille University | Dridi K.,Aix - Marseille University | Jannin V.,Gattefosse SAS | Carriere F.,Aix - Marseille University
Therapeutic Delivery | Year: 2012

Many of the compounds present in lipid-based drug-delivery systems are esters, such as acylglycerols, phospholipids, polyethyleneglycol mono- and di-esters and polysorbate, which can be hydrolyzed by the various lipolytic enzymes present in the GI tract. Lipolysis of these compounds, along with dietary fats, affects the solubility, dispersion and bioavailibity of poorly water-soluble drugs. Pharmaceutical scientists have been taking a new interest in fat digestion in this context, and several studies presenting in vitro gastrointestinal lipolysis models have been published. In most models, it is generally assumed that pancreatic lipase is the main enzyme involved in the gastrointestinal lipolysis of lipid formulations. It was established, however, that gastric lipase, pancreatic carboxyl ester hydrolaze and pancreatic lipase-related protein 2 are the major players involved in the lipolysis of lipid excipients containing acylglycerols and polyethyleneglycol esters. These findings have shown that the lipolysis of lipid excipients may actually start in the stomach and involve several lipolytic enzymes. These findings should therefore be taken into account when testing in vitro the dispersion and bioavailability of poorly water-soluble drugs formulated with lipids. In this review, we present the latest data available about the lipolytic enzymes involved in gastrointestinal lipolysis and suggest tracks for designing physiologically relevant in vitro digestion models. © 2012 Future Science Ltd.

Vithani K.,University of Greenwich | Cuppok Y.,Gattefosse SAS | Mostafa S.,Gattefosse Arc House | Slipper I.J.,University of Greenwich | And 2 more authors.
Pharmaceutical Development and Technology | Year: 2014

Sustained release diclofenac sodium (Df-Na) solid lipid matrices with Compritol® 888 ATO were developed in this study. The drug/lipid powders were processed via cold and hot melt extrusion at various drug loadings. The influence of the processing temperatures, drug loading and the addition of excipients on the obtained dissolution rates was investigated. The physicochemical characterization of the extruded batches showed the existence of crystalline drug in the extrudates with a small amount being solubilized in the lipid matrix. The drug content and uniformity on the tablet surface were also investigated by using energy dispersive X-ray microanalysis. The dissolution rates were found to depend on the actual Df-Na loading and the nature of the added excipients, while the effect of the processing temperatures was negligible. The dissolution mechanism of all extruded formulations followed Peppas- Korsemeyer law, based on the estimated determination coefficients and the dissolution constant rates, indicating drug diffusion from the lipid matrices. © 2014 Informa Healthcare USA, Inc.

Qi S.,University of East Anglia | Marchaud D.,Gattefosse SAS | Craig D.Q.M.,University of East Anglia
Journal of Pharmaceutical Sciences | Year: 2010

The production and physicochemical characterisation of spray chilled Gelucire 50/13 microspheres is described with a view to improving the dissolution of a poorly water-soluble drug, piroxicam, and understanding the fundamental mechanisms associated with the improved drug release. Thermorheological testing was developed as a fast screening method for predicting the processability of dispersions for spray chilling preparation. Spray chilled piroxicam loaded microspheres were spherical in shape with a median diameter of circa 150 mm. DSC indicated no interaction between piroxicam and lipid matrix, while HSM studies performed in polarized light mode indicated that the spheres contained distinct drug crystals. Polarising light microscopy and small-angle XRD investigations on the hydration behaviour of the lipid and the spray chilled microspheres revealed the formation of liquid crystalline phases depending on the degree of hydration. The dissolution behaviour of the piroxicam loaded microspheres showed significant improvements compared to drug alone. The particle size, drug loading and aging of the microspheres were all found to have an influence on the release behaviour. It was proposed that Gelucire 50/13 microspheres release the entrapped piroxicam via formation of a lyotropic liquid crystalline phase, which allows dissolution of the drug particles in a finely divided, high surface area and well-wetted state. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association.

Jannin V.,Gattefosse SAS | Rodier J.-D.,Gattefosse SAS | Musakhanian J.,West Corporation
International Journal of Pharmaceutics | Year: 2014

Lipid-based formulations are a viable option to address modern drug delivery challenges such as increasing the oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs), or sustaining the drug release of molecules intended for chronic diseases. Esters of fatty acids and glycerol (glycerides) and polyethylene-glycols (polyoxylglycerides) are two main classes of lipid-based excipients used by oral, dermal, rectal, vaginal or parenteral routes. These lipid-based materials are more and more commonly used in pharmaceutical drug products but there is still a lack of understanding of how the manufacturing processes, processing aids, or additives can impact the chemical stability of APIs within the drug product. In that regard, this review summarizes the key parameters to look at when formulating with lipid-based excipients in order to anticipate a possible impact on drug stability or variation of excipient functionality. The introduction presents the chemistry of natural lipids, fatty acids and their properties in relation to the extraction and refinement processes. Then, the key parameters during the manufacturing process influencing the quality of lipid-based excipients are provided. Finally, their critical characteristics are discussed in relation with their intended functionality and ability to interact with APIs and others excipients within the formulation. © 2014 Published by Elsevier B.V.

Jannin V.,Gattefosse S.A.S. | Cuppok Y.,Gattefosse S.A.S.
International Journal of Pharmaceutics | Year: 2013

Polymer coatings are widely used to provide drug protection, taste masking, coloration and modified drug release. Typically, coating polymers must be diluted or dispersed in solvents (water or organic) prior to coating and gliding agents are commonly added to prevent particle sticking throughout processing. Lipid excipients present an attractive alternative to standard polymer coatings as they only require melting before application directly onto the substrate. Solvent evaporation is not required; consequently powders with very high specific surface areas can be coated rapidly. A number of different lipid excipients can be used in coating and choosing the appropriate excipient for the application requires an understanding of their physico-chemical properties and its associated effect on drug release. © 2012 Elsevier B.V.

Velghe C.,French Institute of Health and Medical Research | Rosiaux Y.,Gattefosse SAS | Marchaud D.,Gattefosse SAS | Siepmann J.,French Institute of Health and Medical Research | Siepmann F.,French Institute of Health and Medical Research
Journal of Controlled Release | Year: 2014

A mechanistically realistic mathematical model is presented allowing for the quantification of niacin release from lipid tablets, based on glyceryl dibehenate. The systems were prepared either by direct compression or via hot-melt extrusion/grinding/compression. The model assumptions are based on a thorough physico-chemical characterization of the tablets before and after exposure to the release medium. Importantly, the model allows for the first time for the quantitative prediction of the effects of the composition, dimensions and type of preparation method of the tablets on the resulting niacin release kinetics. These quantitative theoretical model predictions were confirmed by several sets of independent experimental results. Furthermore, in silico simulations revealed the fundamental importance of limited niacin solubility within the lipid tablets: during major parts of the release periods, very steep concentration gradients exist and net vitamin flux is restricted to specific regions within the tablets. © 2013 Elsevier B.V.

Jannin V.,Gattefosse S.A.S. | Lemagnen G.,University of Bordeaux Segalen | Gueroult P.,University of Bordeaux Segalen | Larrouture D.,University of Bordeaux Segalen | Tuleu C.,University College London
Advanced Drug Delivery Reviews | Year: 2014

The rectal route can be considered a good alternative to the oral route for the paediatric population because these dosage forms are neither to be swallowed nor need to be taste-masked. Rectal forms can also be administered in an emergency to unconscious or vomiting children. Their manufacturing cost is low with excipients generally regarded as safe. Some new formulation strategies, including mucoadhesive gels and suppositories, were introduced to increase patient acceptability. Even if recent paediatric clinical studies have demonstrated the equivalence of the rectal route with others, in order to enable the use of this promising route for the treatment of children in the 21st Century, some effort should be focused on informing and educating parents and care givers. This review is the first ever to address all the aforementioned items, and to list all drugs used in paediatric rectal forms in literature and marketed products in developed countries. © 2014 Elsevier B.V.

Jannin V.,Gattefosse SAS | Rosiaux Y.,Gattefosse SAS | Doucet J.,Joseph Fourier University
Journal of Controlled Release | Year: 2015

Lipid excipients are more and more commonly used in the pharmaceutical industry as sustained drug delivery agents. However, their development may still be hindered by the well-known polymorphism of lipids which is perceived as a disadvantage with possible impact on drug release upon storage. In order to explore the eventual link between drug release modification and lipid polymorphism, we used a synchrotron radiation-based micro X-ray diffraction that allows probing the crystalline structures of the lipid matrix-forming excipient at a local scale and scanning it across the whole tablet. This technique demonstrated that only one polymorph of Compritol® 888 ATO is present in each tablet. This polymorph is identical whatever the compression force applied during the manufacturing is, and stays the same after storage at 40°C for 45 days, even if these tablets exhibit different drug release profiles. Hence modification of drug release observed after storage is not due to lipid polymorphism. Implementation of post-compression thermal treatments generates another lipid polymorph. Again drug release is not linked with polymorphism because two different polymorphs of Compritol® 888 ATO lead to exactly the same dissolution profile. Variation of drug release observed during storage in accelerated conditions could be attributed to an altered distribution of the lipid component within the matrix structure. The lipid may flow within the matrix structure and increase the hydrophobicity of tablets. © 2014 Elsevier B.V. All rights reserved.

Rosiaux Y.,Gattefosse S.A.S. | Jannin V.,Gattefosse S.A.S. | Hughes S.,Gattefosse S.A.S. | Marchaud D.,Gattefosse S.A.S.
Journal of Controlled Release | Year: 2014

Lipid excipients are attracting interest from drug developers due to their performance, ease of use, versatility and their potential to generate intellectual property through innovation in drug delivery particularly in the case of modifying drug release systems. Many articles have described the use of lipid excipients to develop matrix modified release dosage forms in a range of processing techniques, therefore a comprehensive review is timely to collect together and analyze key information. This review article focuses on the utility of lipid excipients in solid sustained drug delivery systems with emphasis on the efficiency and robustness of these systems with respect to: (i) the choice of the manufacturing process and impact on drug release, (ii) the fundamental drug release mechanisms, (iii) resistance of the drug formulation under physiological conditions and (iv) long-term stability. Understanding the functionality of these versatile excipients in formulation is elementary for the development of highly robust lipid-based sustained release medicines. © 2014 Elsevier B.V.

Cell culture process includes seeding a suitable culture medium with enterocytes and then, after a delay, seeding the medium containing the enterocytes that have begun to proliferate, with goblet cells.

Loading Gattefosse SAS collaborators
Loading Gattefosse SAS collaborators