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Eur J Pharm Sci ; 97: 218-226, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27916693


Pyridoclax is an original oligopyridine lead, very promising in treatment of chemoresistant cancers. However, from solubility measurement and permeability evaluation, it appeared that this compound can be considered as a BCS II drug, with a poor water solubility. To overcome this unfavorable property, two strategies were proposed and compared: pyridoclax di-hydrochloride salt synthesis and formulation of pyridoclax-loaded nanoemulsions (PNEs) efficiently performed by transposing the spontaneous emulsification process previously developed by our team. Whereas the salt improved the thermodynamic solubility of the drug by a factor 4, the apparent solubility of the encapsulated pyridoclax was 1000-fold higher. Their stability was assessed upon dilution in various complex biomimetic media relevant for oral administration (SGF, FaSSIF-V2, FeSSIF-V2) or for the intravenous route (PBS). The solubility of the salt was affected by the nature of the medium, indicating that it could precipitate after administration, negatively impacting its bioavailability and its efficiency in vivo. On the contrary, in all media, PNEs remained stable in terms of granulometric properties (determined by DLS), ζ-potential and encapsulation efficiency (measured by HPLC). Thus, such nanomedicines appear as a valuable option to perform preclinical studies on the promising pyridoclax.

Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Piridinas/síntese química , Cloreto de Sódio/síntese química , Composição de Medicamentos , Emulsões , Nanopartículas/administração & dosagem , Piridinas/administração & dosagem , Cloreto de Sódio/administração & dosagem , Solubilidade
Int J Pharm ; 498(1-2): 49-65, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26685727


The formulate-ability of six model active pharmaceutical ingredients (API), with different physico-chemical profiles, in a nanoemulsion designed to be intraveinously administrable was explored. Nanoemulsions were spontaneously generated at room temperature by pouring a phosphate buffer in an anhydrous mixture containing pharmaceutically acceptable triglycerides and non-ionic surfactants. After determination of the apparent solubility of each API in excipients and characterization of mixtures by DSC, API-loaded nanoemulsions were formulated and characterized in terms of granulometric properties, surface potential, drug recovery efficiency, pH, osmolarity, in vitro drug release, and stability. Except ciprofloxacin, a BCS class IV drug, all studied APIs were soluble in at least one excipient used, i.e. Labrasol. At 2 wt% API, all drug-loaded nanoemulsions present properties compatible with i.v. administration. The formulation should permit to increase apparent solubility of poorly water-soluble APIs, and also to prolong delivery of hydrophobic as well of more hydrophilic compounds. Herein, the relative affinity of the API for nanodroplets and the release medium would directly influence drug release profiles. Nanoemulsions were stable for 7 days. They could also been extemporaneously reconstituted before use. Such a versatile nanoemulsion would provide a valuable option as formulation strategy for improvement of drug properties.

Química Farmacêutica/métodos , Nanopartículas/química , Tensoativos/química , Avaliação Pré-Clínica de Medicamentos/métodos , Emulsões , Glicerídeos/química , Glicerídeos/farmacocinética , Nanopartículas/metabolismo , Tensoativos/farmacocinética