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Achouri D.,Aix - Marseille University | Achouri D.,Laboratoire Of Pharmacie Galenique Industrielle Et Cosmetologie | Alhanout K.,Aix - Marseille University | Alhanout K.,Laboratoire Of Pharmacie Galenique Industrielle Et Cosmetologie | And 5 more authors.
Drug Development and Industrial Pharmacy | Year: 2013

Amongst the various routes of drug delivery, the field of ocular drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. Recent research has focused on the characteristic advantages and limitations of the various drug delivery systems, and further research will be required before the ideal system can be developed. Administration of drugs to the ocular region with conventional delivery systems leads to short contact time of the formulations on the epithelium and fast elimination of drugs. This transient residence time involves poor bioavailability of drugs which can be explained by the tear production, non-productive absorption and impermeability of corneal epithelium. Anatomy of the eye is shortly presented and is connected with ophthalmic delivery and bioavailability of drugs. In the present update on ocular dosage forms, chemical delivery systems such as prodrugs, the use of cyclodextrins to increase solubility of various drugs, the concept of penetration enhancers and other ocular drug delivery systems such as polymeric gels, bioadhesive hydrogels, in-situ forming gels with temperature-, pH-, or osmotically induced gelation, combination of polymers and colloidal systems such as liposomes, niosomes, cubosomes, microemulsions, nanoemulsions and nanoparticles are discussed. Novel ophthalmic delivery systems propose the use of many excipients to increase the viscosity or the bioadhesion of the product. New formulations like gels or colloidal systems have been tested with numerous active substances by in vitro and in vivo studies. Sustained drug release and increase in drug bioavailability have been obtained, offering the promise of innovation in drug delivery systems for ocular administration. Combining different properties of pharmaceutical formulations appears to offer a genuine synergy in bioavailability and sustained release. Promising results are obtained with colloidal systems which present very comfortable conditions of use and prolonged action. © 2013 Informa Healthcare USA, Inc.


Achouri D.,Aix - Marseille University | Achouri D.,Laboratoire Of Pharmacie Galenique Industrielle Et Cosmetologie | Sergent M.,CNRS Analytical Sciences Lab | Tonetto A.,Aix - Marseille University | And 5 more authors.
Drug Development and Industrial Pharmacy | Year: 2015

In the field of keratoconus treatment, a lipid-based liquid crystal nanoparticles system has been developed to improve the preocular retention and ocular bioavailability of riboflavin, a water-soluble drug. The formulation of this ophthalmic drug delivery system was optimized by a simplex lattice experimental design. The delivery system is composed of three main components that are mono acyl glycerol (monoolein), poloxamer 407 and water and two secondary components that are riboflavin and glycerol (added to adjust the osmotic pressure). The amounts of these three main components were selected as the factors to systematically optimize the dependent variables that are the encapsulation efficiency and the particle size. In this way, 12 formulas describing experimental domain of interest were prepared. Results obtained using small angle X-rays scattering (SAXS) and cryo-transmission electron microscopy (cryo-TEM) evidenced the presence of nano-objects with either sponge or hexagonal inverted structure. In the zone of interest, the percentage of each component was determined to obtain both high encapsulation efficiency and small size of particles. Two optimized formulations were found: F7 and F1. They are very close in the ternary phase diagram as they contain 6.83% of poloxamer 407; 44.18% and 42.03% of monoolein; 46.29% and 48.44% of water for F7 and F11, respectively. These formulations displayed a good compromise between inputs and outputs investigated. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.


Achouri D.,Aix - Marseille University | Achouri D.,Laboratoire Of Pharmacie Galenique Industrielle Et Cosmetologie | Hornebecq V.,Aix - Marseille University | Piccerelle P.,Aix - Marseille University | And 4 more authors.
Drug Development and Industrial Pharmacy | Year: 2015

To develop self-assembled liquid crystalline nanoparticles as a drug delivery system for keratoconus treatment, a formulation containing riboflavin a water-soluble drug, two surfactants (poloxamer 407 and mono acyl glycerol-monoolein-) and water was optimized and prepared by emulsification and a homogenization process. A fractional factorial design was applied to estimate the main effects and interaction effects of five parameters on two responses, namely particle size and encapsulation efficiency. The five parameters are the temperature of the two phases, the duration of emulsification, the presence of heating during homogenization, the number of passes and pressure. The most influent parameters are the presence of heating during the homogenization and the pressure that led to the production of nanoparticles with an average size of 145nm and an average encapsulation efficiency of 46%. © 2015 Informa Healthcare USA, Inc. All rights reserved.


Mostefa Side Larbi M.A.,Laboratoire Of Pharmacie Galenique Industrielle Et Cosmetologie | Mostefa Side Larbi M.A.,Aix - Marseille University | Mostefa Side Larbi M.A.,French Institute of Health and Medical Research | Sauzet C.,Laboratoire Of Pharmacie Galenique Industrielle Et Cosmetologie | And 6 more authors.
Journal of Chemical Thermodynamics | Year: 2016

Bisphosphonates (BPs) are widely used to treat calcium disorders because of their structural and functional similarities with the organic pyrophosphates present in plasma and urine. BPs are well known for their strong interactions with calcium, and they have been shown to bind to hydroxyapatite or bone; however, no model exists for studying in greater detail how BPs and particularly amino-bisphosphonates (N-BPs) such as zolendronate (Zol) bind to free calcium. The aim of this work was to determine the effect of pH on Ca2+/Zol complex formation using isothermal titration calorimetry (ITC) because these effects might have important implications for the future development of a solid dosage form. In this study, using a predictive model, we can observe, the existence of three Ca2+/Zol complexes. Knowledge of the binding constant for each complex is helpful for predicting the predominance of the different species at different Ca2+/Zol ratios. Binding is due to ionic interaction between Ca2+ and the negative charges formed by dissociated Zol as a function of the pKa. Ca2+ fixation induces a strong rearrangement of the surrounding water molecules and causes proton release or uptake. The pH-dependent affinity of calcium for each site based on the model used in this work is proposed in detail, which might facilitate the development of new bisphosphonates and enable further elucidation of their mode of action. © 2016 Elsevier Ltd. All rights reserved.

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