RESUMO
The intra-buccal polymeric bioadhesive systems that can stay adhered to the oral soft tissues for drug programmed release, with the preventive and/or therapeutic purpose has been employed for large clinical situations. A system based on hydroxypropyl methyl cellulose/Carbopol 934'/magnesium stearate (HPMC/Cp/StMg) was developed having the sodium fluoride as active principle. This kind of system was evaluated according to its resistance to the removal by means of physical test of tensile strength. Swine buccal mucosa extracted immediately after animals' sacrifice was employed as substrate for the physical trials, to obtain 16 test bodies. Artificial saliva with or without mucin was used to involve the substrate/bioadhesive system sets during the trials. Artificial salivas viscosity was determined by means of Brookfield viscometer, showing the artificial saliva with mucin 10.0 cP, and the artificial saliva without mucin 7.5 cP. The tensile strength assays showed the following averages: for the group "artificial saliva with mucin" - 12.89 Pa, and for the group "without mucin" - 12.35 Pa. Statistical analysis showed no significant difference between the assays for both artificial salivas, and it was possible to conclude that the variable mucin did not interfered with the bioadhesion process for the polymeric devices. The device was able to release fluoride in a safe, efficient and constant way up to 8 hours.
Los sistemas bioadhesivos poliméricos intra-bucales pueden permanecer adheridos a los tejidos blandos orales para una liberación programada de fármacos, con finalidad preventiva y/o propósito terapéutico han sido empleados en diversas situaciones clínicas. Un sistema basado en Hidroxipropilmetilcelulosa/Carbopol934Ô/ estearato de magnesio (HPMC/Cp/StMg) fue desarrollado con fluorato de sodio como principio activo. Este tipo de sistema fue evaluado de acuerdo a su resistencia a la eliminación física por medio de pruebas de resistencia a la tracción. Mucosas bucales de cerdos fueron tomadas inmediatamente después del sacrificio de los animales y se utilizaron como sustrato para las pruebas físicas, obteniendo 16 cuerpos de prueba. Saliva artificial con o sin mucina fue utilizada para participar como parte del sistema sustrato/bioadesivo durante los ensayos. La viscosidad de la saliva artificial, se determinó mediante un viscosímetro Brookfield, mostrando la saliva artificial con mucina 10,0 cP y saliva artificial sin mucina 7,5 cP. Las pruebas de resistencia a la tracción mostraron los siguientes promedios: para la "saliva artificial con mucina" - 12,89 Pa, y para el grupo "sin mucina" - 12,35 Pa. El análisis estadístico no mostró diferencias significativas entre las pruebas de saliva artificial, y es posible concluir que la variable de mucina no interfiere con el proceso de bioadhesión del dispositivo polimérico. El dispositivo fue capaz de liberar fluor de forma segura, eficiente y constante durante un máximo de hasta 8 horas.
Assuntos
Animais , Masculino , Adulto , Flúor/análise , Mucosa Bucal/anatomia & histologia , Mucosa Bucal , Suínos/anatomia & histologia , Suínos/classificação , Suínos/fisiologia , Condicionamento de Tecido Mole Oral/métodos , Mucinas/administração & dosagem , Sistemas de Liberação de Medicamentos/métodosRESUMO
Reverse cubic and hexagonal phases of monoolein have been studied as drug delivery systems. The present study was aimed at investigating whether these systems enhance the cutaneous penetration of cyclosporin A (CysA) in vitro (using porcine ear skin) and in vivo (using hairless mice). Different mesophases were obtained depending on CysA concentration. CysA at 4% allowed the formation of reverse cubic and hexagonal phases in a temperature range of 25-40 degrees C. At 8%, CysA induced the formation of other phases, which might be due to an interaction between the polar groups of the peptide and monoolein. In vitro, the cubic phase increased the penetration of CysA in the stratum corneum (SC) and epidermis plus dermis ([E+D]) at 12 h post-application. The reverse hexagonal phase increased CysA penetration in [E+D] at 6 h and percutaneous delivery at 7.5 h post-application. In vivo, both liquid crystalline phases increased CysA skin penetration. Topical application of these systems, though, induced skin irritation after a 3-day exposure. These results demonstrate that liquid crystalline systems of monoolein are effective in optimizing the delivery of peptides to the skin. The skin irritation observed after topical application of cubic and hexagonal phases should be minimized for their safe use as topical delivery systems.
Assuntos
Ciclosporina/administração & dosagem , Glicerídeos/química , Animais , Cromatografia Líquida de Alta Pressão , Cristalização , Ciclosporina/química , Ciclosporina/farmacocinética , Técnicas In Vitro , Camundongos , Camundongos Pelados , Pele/efeitos dos fármacos , Pele/metabolismo , Absorção Cutânea , Espectroscopia de Infravermelho com Transformada de Fourier , Água/química , Difração de Raios XRESUMO
Topical delivery of cyclosporin A (CysA) is of great interest for the treatment of autoimmune skin disorders, but it is frequently ineffective due to poor drug penetration in the skin. The present study was aimed at investigating whether the presence of monoolein (a lipidic penetration enhancer) in a preparation of propylene glycol can improve CysA delivery to the skin. CysA was incorporated in a propylene glycol preparation containing 5-70% (w/w) of monoolein. The topical (to the skin) and transdermal (across the skin) delivery of CysA were evaluated in vitro using porcine ear skin mounted in a Franz diffusion cell. CysA was quantified by UV-HPLC. At 5%, monoolein increased only the transdermal delivery of CysA. At 10%, it increased both topical and transdermal delivery. When the concentration of monoolein was further increased (20-70% w/w), an interesting phenomenon was observed: the topical delivery of CysA was still elevated but its transdermal delivery was substantially reduced. It was concluded that monoolein (in propylene glycol formulations) can promote the topical delivery of CysA, with reduced transdermal delivery.
Assuntos
Ciclosporina/administração & dosagem , Ciclosporina/farmacocinética , Glicerídeos/farmacologia , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Administração Tópica , Animais , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Difusão , Excipientes , Técnicas In Vitro , Lipídeos/química , Masculino , Solubilidade , SuínosRESUMO
Glyceryl monooleate/water cubic phase systems were investigated as drug delivery systems, using salicylic acid as a model drug. The liquid crystalline phases formed by the glyceryl monooleate (GMO)/water systems were characterized by polarizing microscopy. In vitro drug release studies were performed and the influences of initial water content, swelling and drug loading on the drug release properties were evaluated. Water uptake followed second-order swelling kinetics. In vitro release profiles showed Fickian diffusion control and were independent on the initial water content and drug loading, suggesting GMO cubic phase gels suitability for use as drug delivery system.
Assuntos
Portadores de Fármacos/farmacocinética , Géis/farmacocinética , Portadores de Fármacos/química , Géis/químicaRESUMO
A liberaçäo transdérmica de muitos fármacos é dificultada pelas características de barreira do estrato córneo. Promotores químicos de absorçäo cutânea säo capazes de interagir com os constituintes do estrato córneo, induzindo aumento temporário e reversível na permeabilidade da pele. O objetivo deste trabalho foi avaliar a influência de sistemas monoleína (monoleato de glicerol)/solventes na absorçäo percutânea de um fármaco lipofílico (a progesterona), através do estrato córneo de camundongos sem pelo, bem como o efeito da monoleína nas características estruturais do estrato córneo, por meio de microscopia eletrônica de varredura...