Ghania Degobert - Academia.edu (original) (raw)

Papers by Ghania Degobert

Research paper thumbnail of Study and optimization of freeze-drying cycles of a model probiotic strain

Proceedings of 21th International Drying Symposium, Sep 11, 2018

This work is based on the experimental study of the freeze-drying process to understand the impac... more This work is based on the experimental study of the freeze-drying process to understand the impact of numerous factors on the survival rates of a model probiotic strain of Lactobacillus casei type. With the aim to find out if cell density in the matrix and survival rates are linked, we have studied the location of the cells after freeze drying inside a porous matrix composed of a lactose basis with a polymer, the polyvinylpyrrolidone (PVP) in various amounts. The best survival rate were obtained at slow freezing rate for a formulation containing 5% (m/V) of lactose and 5% (m/V) of PVP.

Research paper thumbnail of Lyophilization of Nanocapsules: Instability Sources, Formulation and Process Parameters

Pharmaceutics

Polymeric nanocapsules have gained more and more interest in the medical sciences. Their core-she... more Polymeric nanocapsules have gained more and more interest in the medical sciences. Their core-shell structure offers numerous advantages, especially regarding their use as drug delivery systems. This review begins by presenting the different intrinsic sources of the instability of nanocapsules. The physical and chemical potential instabilities of nanocapsules reduce their shelf-life and constitute a barrier to their clinical use and to their commercialization. To overcome these issues, lyophilization is often used as a process of choice in the pharmaceutical industry especially when labile compounds are used. The state of the art of lyophilization nanocapsules is reviewed. The formulation properties and the process parameters are discussed for a complete understanding of their impact on the stability and storage of the final dried product. To assess the quality of the dried product, various characterization methods are also discussed.

Research paper thumbnail of Experimental study and optimization of freeze-drying cycles of a model Casei type probiotic bacteria

Research paper thumbnail of Thermodynamic Properties and Water States in Ternary PVP/Lactose/Water Frozen Systems

Journal of Chemical & Engineering Data

Research paper thumbnail of Spray-drying Nanocapsules in Presence of Colloidal Silica as Drying Auxiliary Agent: Formulation and Process Variables Optimization Using Experimental Designs

Pharmaceutical Research, 2007

Research paper thumbnail of Synthesis and characterisation of novel nanospheres made from amphiphilic perfluoroalkylthio-β-cyclodextrins

European Journal of Pharmaceutics and Biopharmaceutics, 2005

Research paper thumbnail of Freeze-drying of nanoparticles: Formulation, process and storage considerations

Advanced Drug Delivery Reviews, Dec 30, 2006

Freeze-drying has been considered as a good technique to improve the long-term stability of collo... more Freeze-drying has been considered as a good technique to improve the long-term stability of colloidal nanoparticles. The poor stability in an aqueous medium of these systems forms a real barrier against the clinical use of nanoparticles. This article reviews the state of the art of freeze-drying nanoparticles. It discusses the most important parameters that influence the success of freeze-drying of these fragile systems, and provides an overview of nanoparticles freeze-drying process and formulation strategies with a focus on the impact of formulation and process on particle stability.

Research paper thumbnail of Freeze-drying of nanocapsules: impact of annealing on the drying process

International Journal of Pharmaceutics, Oct 31, 2006

Freeze-drying process was recently applied to improve the long-term storage stability of nanocaps... more Freeze-drying process was recently applied to improve the long-term storage stability of nanocapsules. Thermal treatment by annealing is an interesting process to optimize a freeze-drying cycle of these colloidal vectors. The objective of this paper is to investigate the impact of annealing on primary and secondary drying characteristics and on nanocapsules (NC) properties. Nanocapsules were prepared from poly--caprolactone (PCL) biodegradable polymer and stabilized by polyvinyl alcohol (PVA), and then freeze-dried with two cryoprotectants: sucrose and poly vinyl pyrrolidone (PVP). Freeze-dried nanocapsules were characterized by size measurement and transmission electron microscopy after reconstitution. The effect of annealing on the kinetics of sublimation, on the mass transfer resistance and on the porosity of the freeze-dried product has been studied in the case of PVP. Finally, the effect of annealing on the kinetic of secondary drying was studied and the results were coupled with the isotherm of sorption. Results showed that PCL nanocapsules could be freeze-dried without any modification of their properties in presence of the two cryoprotectants used. Annealing of nanocapsules suspensions could accelerate the sublimation rate without any modification of nanocapsules size in the case of the two studied cryoprotectants. Such improvement could be explained by the increase of ice crystals size after annealing and by the diminution of mass transfer resistance by the dried layer. The acceleration of sublimation rate seems to depend on the temperature of annealing. The annealing of sucrose solution slows down the secondary drying kinetic whereas no effect is observed in the case of PVP.

Research paper thumbnail of Capsules dures d'hydroxypropyl méthylcellulose : : Une alternative à la gélatine etude comparative de leur adhésivité

Stp Pharma Pratiques, 1999

Research paper thumbnail of Optimization of Freeze-Drying Cycle for Tert-Butanol–Based Formulations of Ibuprofen

Http Dx Doi Org 10 1080 07373937 2012 733789, Feb 17, 2013

ABSTRACT Abstract: We carried out the formulation set-up and thermodynamics as well as morphologi... more ABSTRACT Abstract: We carried out the formulation set-up and thermodynamics as well as morphological characterization of two systems: an aqueous-based formulation and an organic-solvent-based formulation with tert-butanol (TBA) at eutectic composition (20% TBA + water 80% by mass) containing ibuprofen as the model pharmaceutical active component. The goal was to carry out the optimization of a soft freeze-drying cycle for heat-sensitive drugs. The organic-based ibuprofen formulation had a glass transition temperature significantly higher compared to that of the aqueous-based ibuprofen formulation, which allowed much higher sublimation temperatures for these systems in comparison with the pure water-based ibuprofen formulations. The morphological study of the frozen organic-based formulation showed unexpected behavior in comparison with previous literature data reported for water-based formulations. For the same freezing rates, the mean diameters of the solvent crystals of organic-based formulations were much larger than that of ice crystals of aqueous-based formulation, which led to a freeze-dried matrix of higher permeability. In contrast to what was observed with the aqueous-based formulations, the freezing rates, in the range of classical industrial values investigated, had no significant effect on the supercooling of the liquid ibuprofen formulations tested as well as on the nucleation temperatures and on the morphology of the organic solvent crystals. All these singular characteristics, with lower sublimation enthalpies and higher equilibrium vapor pressure values previously measured with the same formulations in our laboratory, explain the large reduction of sublimation times observed during the soft freeze-drying processes for heat-sensitive drugs with organic (TBA)-based formulations.

Research paper thumbnail of Solubility of diazepam in water + tert-butyl alcohol solvent mixtures: Part 1. Experimental data and thermodynamic analysis

Fluid Phase Equilibria, 2015

Research paper thumbnail of Sulfated and non-sulfated amphiphilic-β-cyclodextrins: Impact of their structural properties on the physicochemical properties of nanoparticles

International Journal of Pharmaceutics, 2008

The aim of this work was to study the preparation of nanospheres from amphiphilic beta-cyclodextr... more The aim of this work was to study the preparation of nanospheres from amphiphilic beta-cyclodextrins formed (a) by different acylation degrees (DA) at the secondary hydroxyl face (DA=14 and 21) followed by varying (b) the sulfatation degrees (DS) at the primary hydroxyl face (DS=0, 4 and 7). The physicochemical properties of the synthesized compounds such as molecular weights, the theoretical HLB values and the critical micellar concentration values and their surface area were presented. The nanoparticles prepared from amphiphilic beta-cyclodextrins were characterized by mean size, zeta potential and their morphology. The compounds presented hydrophile-lipophile balance values ranging from 5.6 to 10. For sulfated amphiphilic beta-cyclodextrins having HLB values higher than 8, were able to self-organize in water to form nanoparticles. However, for the amphiphilic beta-cyclodextrins that HLB values lower than 6.6 are insoluble in water but soluble in organic solvents rendering possible the preparation of nanoparticles by nanoprecipitation technique. An interesting correlation between the amphiphilic-beta-cyclodextrin structures and their ability to form nanospheres has been established. The association of sulfated amphiphilic-beta-CDs to the peracylated amphiphilic-beta-CDs was interesting, it led to improve the stability of nanospheres size and probably confer them a biological activity.

Research paper thumbnail of Loading and in vitro release of salbutamol from degradable cross-linked starch microspheres intended for pulmonary administration

S.T.P. Pharma Pratiques

ABSTRACT

Research paper thumbnail of Hydroxypropyl methylcellulose hard capsules: An alternative to gelatin

Research paper thumbnail of Solutions, Suspensions et Emulsions destinées aux voies orale, parentérale et ophtalmique

Research paper thumbnail of Sulfated and non-sulfated amphiphilic-beta-cyclodextrins: impact of their structural properties on the physicochemical properties of nanoparticles

International journal of pharmaceutics, Jan 3, 2008

The aim of this work was to study the preparation of nanospheres from amphiphilic beta-cyclodextr... more The aim of this work was to study the preparation of nanospheres from amphiphilic beta-cyclodextrins formed (a) by different acylation degrees (DA) at the secondary hydroxyl face (DA=14 and 21) followed by varying (b) the sulfatation degrees (DS) at the primary hydroxyl face (DS=0, 4 and 7). The physicochemical properties of the synthesized compounds such as molecular weights, the theoretical HLB values and the critical micellar concentration values and their surface area were presented. The nanoparticles prepared from amphiphilic beta-cyclodextrins were characterized by mean size, zeta potential and their morphology. The compounds presented hydrophile-lipophile balance values ranging from 5.6 to 10. For sulfated amphiphilic beta-cyclodextrins having HLB values higher than 8, were able to self-organize in water to form nanoparticles. However, for the amphiphilic beta-cyclodextrins that HLB values lower than 6.6 are insoluble in water but soluble in organic solvents rendering possibl...

Research paper thumbnail of Enzymatic degradation of epichlorohydrin crosslinked starch microspheres by alpha-amylase

Pharmaceutical research, 1999

The influence of chemical parameters on the sensitivity to enzymatic degradation by alpha-amylase... more The influence of chemical parameters on the sensitivity to enzymatic degradation by alpha-amylase of starch microspheres cross-linked by epichlorohydrin was studied. Starch microspheres were prepared using epichlorohydrin as a crosslinking agent. Their swelling degree, reflecting the number of glycerol diether bridges in the polymeric network, and the number of non-crosslinking monoglycerol ether groups corresponding to a side-reaction of epichlorohydrin with starch were determined. Degradation rates of the microspheres in presence of porcine alpha-amylase were determined by a microvolumetric method. Degradation by alpha-amylase was surface-controlled and could be modulated by the introduction in the polymeric network of: (i) non-hydrolysable alpha-1,6 bonds related to the presence of amylopectin in the raw starch, (ii) glycerol diether and, (iii) monoether groups, all of these being likely to block the activity of alpha-amylase. In the case of highly cross-linked microspheres, the ...

Research paper thumbnail of A pilot study of freeze drying of poly(epsilon-caprolactone) nanocapsules stabilized by poly(vinyl alcohol): Formulation and process optimization

International Journal of Pharmaceutics, 2006

A common limitation of using polymeric nanoparticles in aqueous suspension is due to their poor c... more A common limitation of using polymeric nanoparticles in aqueous suspension is due to their poor chemical and physical stability when conserved for a long time. Therefore, freeze drying of these colloidal systems is an alternative method to achieve long-term stability. Nanocapsules have thin and fragile shell structure, which may not resist to the stress of such process. The aim of this study is to investigate the formulation and process parameters in order to ensure the stability of polycaprolactone nanocapsules (PCL NC) by freeze drying.

Research paper thumbnail of Freeze-drying of nanocapsules: Impact of annealing on the drying process

International Journal of Pharmaceutics, 2006

Freeze-drying process was recently applied to improve the long-term storage stability of nanocaps... more Freeze-drying process was recently applied to improve the long-term storage stability of nanocapsules. Thermal treatment by annealing is an interesting process to optimize a freeze-drying cycle of these colloidal vectors. The objective of this paper is to investigate the impact of annealing on primary and secondary drying characteristics and on nanocapsules (NC) properties. Nanocapsules were prepared from poly--caprolactone (PCL) biodegradable polymer and stabilized by polyvinyl alcohol (PVA), and then freeze-dried with two cryoprotectants: sucrose and poly vinyl pyrrolidone (PVP). Freeze-dried nanocapsules were characterized by size measurement and transmission electron microscopy after reconstitution. The effect of annealing on the kinetics of sublimation, on the mass transfer resistance and on the porosity of the freeze-dried product has been studied in the case of PVP. Finally, the effect of annealing on the kinetic of secondary drying was studied and the results were coupled with the isotherm of sorption. Results showed that PCL nanocapsules could be freeze-dried without any modification of their properties in presence of the two cryoprotectants used. Annealing of nanocapsules suspensions could accelerate the sublimation rate without any modification of nanocapsules size in the case of the two studied cryoprotectants. Such improvement could be explained by the increase of ice crystals size after annealing and by the diminution of mass transfer resistance by the dried layer. The acceleration of sublimation rate seems to depend on the temperature of annealing. The annealing of sucrose solution slows down the secondary drying kinetic whereas no effect is observed in the case of PVP.

Research paper thumbnail of Formulation of epichlorohydrin cross-linked starch microspheres

Journal of Microencapsulation, 2001

The present work describes a water/oil emulsion technique for the production of microspheres by c... more The present work describes a water/oil emulsion technique for the production of microspheres by cross-linking soluble starch with epichlorohyrin, which is a very e cient divalent cross-linking agent for starch. Because they are important features for potential applications, such as pulmonary administration, special attention has been paid to control the mean particle size and size distribution. Microspheres ranging from 0.3±250 mm with narrow size distributions could be obtained. Due to the strongly basic nature of the aqueous phase, no stable emulsions could be obtained in the water/oil emulsion domains. In this context, the stirring rate during the emulsi®cation step was crucial for controlling the particle size. Additionally, a high organic-to-aqueous phase ratio and the presence of a surfactant agent helped to prevent the coalescence of the droplets during the formation of the microspheres. The process was not sensitive to modi®cations of the chemical conditions, such as the cross-linking ratio, which allows variation of the chemical nature of the polymer forming the core of the microspheres without modifying their morphological characteristics.

Research paper thumbnail of Study and optimization of freeze-drying cycles of a model probiotic strain

Proceedings of 21th International Drying Symposium, Sep 11, 2018

This work is based on the experimental study of the freeze-drying process to understand the impac... more This work is based on the experimental study of the freeze-drying process to understand the impact of numerous factors on the survival rates of a model probiotic strain of Lactobacillus casei type. With the aim to find out if cell density in the matrix and survival rates are linked, we have studied the location of the cells after freeze drying inside a porous matrix composed of a lactose basis with a polymer, the polyvinylpyrrolidone (PVP) in various amounts. The best survival rate were obtained at slow freezing rate for a formulation containing 5% (m/V) of lactose and 5% (m/V) of PVP.

Research paper thumbnail of Lyophilization of Nanocapsules: Instability Sources, Formulation and Process Parameters

Pharmaceutics

Polymeric nanocapsules have gained more and more interest in the medical sciences. Their core-she... more Polymeric nanocapsules have gained more and more interest in the medical sciences. Their core-shell structure offers numerous advantages, especially regarding their use as drug delivery systems. This review begins by presenting the different intrinsic sources of the instability of nanocapsules. The physical and chemical potential instabilities of nanocapsules reduce their shelf-life and constitute a barrier to their clinical use and to their commercialization. To overcome these issues, lyophilization is often used as a process of choice in the pharmaceutical industry especially when labile compounds are used. The state of the art of lyophilization nanocapsules is reviewed. The formulation properties and the process parameters are discussed for a complete understanding of their impact on the stability and storage of the final dried product. To assess the quality of the dried product, various characterization methods are also discussed.

Research paper thumbnail of Experimental study and optimization of freeze-drying cycles of a model Casei type probiotic bacteria

Research paper thumbnail of Thermodynamic Properties and Water States in Ternary PVP/Lactose/Water Frozen Systems

Journal of Chemical & Engineering Data

Research paper thumbnail of Spray-drying Nanocapsules in Presence of Colloidal Silica as Drying Auxiliary Agent: Formulation and Process Variables Optimization Using Experimental Designs

Pharmaceutical Research, 2007

Research paper thumbnail of Synthesis and characterisation of novel nanospheres made from amphiphilic perfluoroalkylthio-β-cyclodextrins

European Journal of Pharmaceutics and Biopharmaceutics, 2005

Research paper thumbnail of Freeze-drying of nanoparticles: Formulation, process and storage considerations

Advanced Drug Delivery Reviews, Dec 30, 2006

Freeze-drying has been considered as a good technique to improve the long-term stability of collo... more Freeze-drying has been considered as a good technique to improve the long-term stability of colloidal nanoparticles. The poor stability in an aqueous medium of these systems forms a real barrier against the clinical use of nanoparticles. This article reviews the state of the art of freeze-drying nanoparticles. It discusses the most important parameters that influence the success of freeze-drying of these fragile systems, and provides an overview of nanoparticles freeze-drying process and formulation strategies with a focus on the impact of formulation and process on particle stability.

Research paper thumbnail of Freeze-drying of nanocapsules: impact of annealing on the drying process

International Journal of Pharmaceutics, Oct 31, 2006

Freeze-drying process was recently applied to improve the long-term storage stability of nanocaps... more Freeze-drying process was recently applied to improve the long-term storage stability of nanocapsules. Thermal treatment by annealing is an interesting process to optimize a freeze-drying cycle of these colloidal vectors. The objective of this paper is to investigate the impact of annealing on primary and secondary drying characteristics and on nanocapsules (NC) properties. Nanocapsules were prepared from poly--caprolactone (PCL) biodegradable polymer and stabilized by polyvinyl alcohol (PVA), and then freeze-dried with two cryoprotectants: sucrose and poly vinyl pyrrolidone (PVP). Freeze-dried nanocapsules were characterized by size measurement and transmission electron microscopy after reconstitution. The effect of annealing on the kinetics of sublimation, on the mass transfer resistance and on the porosity of the freeze-dried product has been studied in the case of PVP. Finally, the effect of annealing on the kinetic of secondary drying was studied and the results were coupled with the isotherm of sorption. Results showed that PCL nanocapsules could be freeze-dried without any modification of their properties in presence of the two cryoprotectants used. Annealing of nanocapsules suspensions could accelerate the sublimation rate without any modification of nanocapsules size in the case of the two studied cryoprotectants. Such improvement could be explained by the increase of ice crystals size after annealing and by the diminution of mass transfer resistance by the dried layer. The acceleration of sublimation rate seems to depend on the temperature of annealing. The annealing of sucrose solution slows down the secondary drying kinetic whereas no effect is observed in the case of PVP.

Research paper thumbnail of Capsules dures d'hydroxypropyl méthylcellulose : : Une alternative à la gélatine etude comparative de leur adhésivité

Stp Pharma Pratiques, 1999

Research paper thumbnail of Optimization of Freeze-Drying Cycle for Tert-Butanol–Based Formulations of Ibuprofen

Http Dx Doi Org 10 1080 07373937 2012 733789, Feb 17, 2013

ABSTRACT Abstract: We carried out the formulation set-up and thermodynamics as well as morphologi... more ABSTRACT Abstract: We carried out the formulation set-up and thermodynamics as well as morphological characterization of two systems: an aqueous-based formulation and an organic-solvent-based formulation with tert-butanol (TBA) at eutectic composition (20% TBA + water 80% by mass) containing ibuprofen as the model pharmaceutical active component. The goal was to carry out the optimization of a soft freeze-drying cycle for heat-sensitive drugs. The organic-based ibuprofen formulation had a glass transition temperature significantly higher compared to that of the aqueous-based ibuprofen formulation, which allowed much higher sublimation temperatures for these systems in comparison with the pure water-based ibuprofen formulations. The morphological study of the frozen organic-based formulation showed unexpected behavior in comparison with previous literature data reported for water-based formulations. For the same freezing rates, the mean diameters of the solvent crystals of organic-based formulations were much larger than that of ice crystals of aqueous-based formulation, which led to a freeze-dried matrix of higher permeability. In contrast to what was observed with the aqueous-based formulations, the freezing rates, in the range of classical industrial values investigated, had no significant effect on the supercooling of the liquid ibuprofen formulations tested as well as on the nucleation temperatures and on the morphology of the organic solvent crystals. All these singular characteristics, with lower sublimation enthalpies and higher equilibrium vapor pressure values previously measured with the same formulations in our laboratory, explain the large reduction of sublimation times observed during the soft freeze-drying processes for heat-sensitive drugs with organic (TBA)-based formulations.

Research paper thumbnail of Solubility of diazepam in water + tert-butyl alcohol solvent mixtures: Part 1. Experimental data and thermodynamic analysis

Fluid Phase Equilibria, 2015

Research paper thumbnail of Sulfated and non-sulfated amphiphilic-β-cyclodextrins: Impact of their structural properties on the physicochemical properties of nanoparticles

International Journal of Pharmaceutics, 2008

The aim of this work was to study the preparation of nanospheres from amphiphilic beta-cyclodextr... more The aim of this work was to study the preparation of nanospheres from amphiphilic beta-cyclodextrins formed (a) by different acylation degrees (DA) at the secondary hydroxyl face (DA=14 and 21) followed by varying (b) the sulfatation degrees (DS) at the primary hydroxyl face (DS=0, 4 and 7). The physicochemical properties of the synthesized compounds such as molecular weights, the theoretical HLB values and the critical micellar concentration values and their surface area were presented. The nanoparticles prepared from amphiphilic beta-cyclodextrins were characterized by mean size, zeta potential and their morphology. The compounds presented hydrophile-lipophile balance values ranging from 5.6 to 10. For sulfated amphiphilic beta-cyclodextrins having HLB values higher than 8, were able to self-organize in water to form nanoparticles. However, for the amphiphilic beta-cyclodextrins that HLB values lower than 6.6 are insoluble in water but soluble in organic solvents rendering possible the preparation of nanoparticles by nanoprecipitation technique. An interesting correlation between the amphiphilic-beta-cyclodextrin structures and their ability to form nanospheres has been established. The association of sulfated amphiphilic-beta-CDs to the peracylated amphiphilic-beta-CDs was interesting, it led to improve the stability of nanospheres size and probably confer them a biological activity.

Research paper thumbnail of Loading and in vitro release of salbutamol from degradable cross-linked starch microspheres intended for pulmonary administration

S.T.P. Pharma Pratiques

ABSTRACT

Research paper thumbnail of Hydroxypropyl methylcellulose hard capsules: An alternative to gelatin

Research paper thumbnail of Solutions, Suspensions et Emulsions destinées aux voies orale, parentérale et ophtalmique

Research paper thumbnail of Sulfated and non-sulfated amphiphilic-beta-cyclodextrins: impact of their structural properties on the physicochemical properties of nanoparticles

International journal of pharmaceutics, Jan 3, 2008

The aim of this work was to study the preparation of nanospheres from amphiphilic beta-cyclodextr... more The aim of this work was to study the preparation of nanospheres from amphiphilic beta-cyclodextrins formed (a) by different acylation degrees (DA) at the secondary hydroxyl face (DA=14 and 21) followed by varying (b) the sulfatation degrees (DS) at the primary hydroxyl face (DS=0, 4 and 7). The physicochemical properties of the synthesized compounds such as molecular weights, the theoretical HLB values and the critical micellar concentration values and their surface area were presented. The nanoparticles prepared from amphiphilic beta-cyclodextrins were characterized by mean size, zeta potential and their morphology. The compounds presented hydrophile-lipophile balance values ranging from 5.6 to 10. For sulfated amphiphilic beta-cyclodextrins having HLB values higher than 8, were able to self-organize in water to form nanoparticles. However, for the amphiphilic beta-cyclodextrins that HLB values lower than 6.6 are insoluble in water but soluble in organic solvents rendering possibl...

Research paper thumbnail of Enzymatic degradation of epichlorohydrin crosslinked starch microspheres by alpha-amylase

Pharmaceutical research, 1999

The influence of chemical parameters on the sensitivity to enzymatic degradation by alpha-amylase... more The influence of chemical parameters on the sensitivity to enzymatic degradation by alpha-amylase of starch microspheres cross-linked by epichlorohydrin was studied. Starch microspheres were prepared using epichlorohydrin as a crosslinking agent. Their swelling degree, reflecting the number of glycerol diether bridges in the polymeric network, and the number of non-crosslinking monoglycerol ether groups corresponding to a side-reaction of epichlorohydrin with starch were determined. Degradation rates of the microspheres in presence of porcine alpha-amylase were determined by a microvolumetric method. Degradation by alpha-amylase was surface-controlled and could be modulated by the introduction in the polymeric network of: (i) non-hydrolysable alpha-1,6 bonds related to the presence of amylopectin in the raw starch, (ii) glycerol diether and, (iii) monoether groups, all of these being likely to block the activity of alpha-amylase. In the case of highly cross-linked microspheres, the ...

Research paper thumbnail of A pilot study of freeze drying of poly(epsilon-caprolactone) nanocapsules stabilized by poly(vinyl alcohol): Formulation and process optimization

International Journal of Pharmaceutics, 2006

A common limitation of using polymeric nanoparticles in aqueous suspension is due to their poor c... more A common limitation of using polymeric nanoparticles in aqueous suspension is due to their poor chemical and physical stability when conserved for a long time. Therefore, freeze drying of these colloidal systems is an alternative method to achieve long-term stability. Nanocapsules have thin and fragile shell structure, which may not resist to the stress of such process. The aim of this study is to investigate the formulation and process parameters in order to ensure the stability of polycaprolactone nanocapsules (PCL NC) by freeze drying.

Research paper thumbnail of Freeze-drying of nanocapsules: Impact of annealing on the drying process

International Journal of Pharmaceutics, 2006

Freeze-drying process was recently applied to improve the long-term storage stability of nanocaps... more Freeze-drying process was recently applied to improve the long-term storage stability of nanocapsules. Thermal treatment by annealing is an interesting process to optimize a freeze-drying cycle of these colloidal vectors. The objective of this paper is to investigate the impact of annealing on primary and secondary drying characteristics and on nanocapsules (NC) properties. Nanocapsules were prepared from poly--caprolactone (PCL) biodegradable polymer and stabilized by polyvinyl alcohol (PVA), and then freeze-dried with two cryoprotectants: sucrose and poly vinyl pyrrolidone (PVP). Freeze-dried nanocapsules were characterized by size measurement and transmission electron microscopy after reconstitution. The effect of annealing on the kinetics of sublimation, on the mass transfer resistance and on the porosity of the freeze-dried product has been studied in the case of PVP. Finally, the effect of annealing on the kinetic of secondary drying was studied and the results were coupled with the isotherm of sorption. Results showed that PCL nanocapsules could be freeze-dried without any modification of their properties in presence of the two cryoprotectants used. Annealing of nanocapsules suspensions could accelerate the sublimation rate without any modification of nanocapsules size in the case of the two studied cryoprotectants. Such improvement could be explained by the increase of ice crystals size after annealing and by the diminution of mass transfer resistance by the dried layer. The acceleration of sublimation rate seems to depend on the temperature of annealing. The annealing of sucrose solution slows down the secondary drying kinetic whereas no effect is observed in the case of PVP.

Research paper thumbnail of Formulation of epichlorohydrin cross-linked starch microspheres

Journal of Microencapsulation, 2001

The present work describes a water/oil emulsion technique for the production of microspheres by c... more The present work describes a water/oil emulsion technique for the production of microspheres by cross-linking soluble starch with epichlorohyrin, which is a very e cient divalent cross-linking agent for starch. Because they are important features for potential applications, such as pulmonary administration, special attention has been paid to control the mean particle size and size distribution. Microspheres ranging from 0.3±250 mm with narrow size distributions could be obtained. Due to the strongly basic nature of the aqueous phase, no stable emulsions could be obtained in the water/oil emulsion domains. In this context, the stirring rate during the emulsi®cation step was crucial for controlling the particle size. Additionally, a high organic-to-aqueous phase ratio and the presence of a surfactant agent helped to prevent the coalescence of the droplets during the formation of the microspheres. The process was not sensitive to modi®cations of the chemical conditions, such as the cross-linking ratio, which allows variation of the chemical nature of the polymer forming the core of the microspheres without modifying their morphological characteristics.