RESUMEN
OBJECTIVE: The aim of the present study was to evaluate the influence of the incorporation of caffeine as a model active ingredient on the quality attributes of a bioadhesive emulgel formulation previously optimized by Quality by Design (QbD) tools. Emulgels are emerging topical drug delivery systems for cosmetic or pharmaceutical uses, which combine the advantages of both emulsions and gels. METHODS: In this work, the observed and predicted values for spreadability, phase separation by centrifugation and detachment forces performed by texturometer were compared with those of the control and active-containing emulgel formulations. In addition, rheological properties, release of caffeine and comparative in vitro/ex vivo bioadhesion properties were evaluated using human skin. RESULTS: The flow curves of emulgel formulations showed the typical pseudoplastic and no thixotropic flow with yield stress. The incorporation of active ingredient did not produce significant changes. All emulgels were uniformly spread and no significant differences in spreadability values between control and caffeine containing formulations and neither respect to those predicted values from experimental design optimization were found. Emulgel formulations showed appropriate detachment forces values and no significant differences between caffeine loading and control emulgel formulations were observed. CONCLUSION: Caffeine was successfully vehiculized in this optimized bioadhesive emulgel formulation, which showed high robustness regarding the process variability. There were no significant changes in the critical quality attributes after the incorporation of the active ingredient and a promising stability was observed for at least one year. Results suggested that the optimized emulgel is an interesting topical biodhesive delivery system for cosmetic applications, including agents for skin conditioning, not present in gels formulations.
OBJECTIF: la présente étude visait à évaluer l'influence de l'incorporation de la caféine comme une substance active modèle dans les attributs de qualité d'une préparation d'émulgel bioadhésif préalablement optimisée grâce à des outils QbD (Quality by Design, Qualité par la conception). Les émulgels sont des systèmes d'administration de médicaments topiques émergents destinés à des usages cosmétiques ou pharmaceutiques, qui associent les avantages des émulsions et des gels. MÉTHODES: dans cet étude, les valeurs observées et prédites en matière d'étalement, de séparation des phases par centrifugation et de forces de détachement par texturomètre ont été comparées à celles des préparations de contrôle et d'émulgel contenant des actifs. En outre, les propriétés rhéologiques, la libération de caféine et la comparaison des propriétés de bioadhérence in vitro / ex vivo ont été évaluées sur la peau humaine. RÉSULTATS: les courbes de débit des préparations d'émulgel révèlent un flux pseudoplastique typique et non thixotropique avec charge d'écoulement. L'incorporation de la substance active n'a pas produit de changements importants. Tous les émulgels ont été uniformément étalés et aucune différence significative dans les valeurs d'étalement entre les préparations de contrôle et celles contenant de la caféine n'a été observée. Aucune différence concernant les valeurs prédites dans l'optimisation de la conception expérimentale n'a été observée. Les préparations d'émulgel ont montré des valeurs de forces de détachement appropriées et aucune différence significative n'a été observée entre les préparations d'émulgel à base de caféine et les préparations de contrôle. CONCLUSION: la caféine a été administrée avec succès dans cette préparation optimisée d'émulgel bioadhésif, qui a affiché une grande résistance en ce qui concerne la variabilité du procédé. Il n'y a pas eu de changement significatif dans les attributs de qualité critiques après l'incorporation de la substance active et une stabilité prometteuse a été observée pendant au moins un an. Les résultats ont suggéré que l'émulgel optimisé est un système d'administration de bioadhérence topique intéressant pour les applications cosmétiques, y compris les agents de revitalisation de la peau qui ne se trouvent pas dans les préparations de gels.
Asunto(s)
Cafeína/química , Cosméticos , Composición de Medicamentos , Diseño de Fármacos , Geles/química , Adhesivos Tisulares/química , HumanosRESUMEN
INTRODUCTION: The use of bioadhesive hydrogels for skin care presents important advantages such as long residence times on the application site and reduced product administration frequency. OBJECT: The aim of the present work was to develop bioadhesive hydrogels for skin application, using caffeine as a model active ingredient. METHODS: Eight hydrogels were formulated using binary combinations of a primary polymer (carbomer homopolymer type C (Carbopol(®) 980) or kappa carrageenan potassium salt (Gelcarin(®) GP-812 NF)) and a secondary polymer (carbomer copolymer type B (Pemulen(™) TR-1), xanthan gum or guar gum). Hydrogels were characterized by means of physico-chemical (dynamic rheological measurements, spreadability and adhesion measurements) and sensory methods (projective mapping in combination with a check-all-that-apply (CATA) question). Caffeine hydrogels were formulated using two of the most promising formulations regarding adhesion properties and sensory characteristics. In vitro active ingredient release studies were carried out. RESULTS: Hydrogel formulations showed a prevalently elastic rheological behaviour. Complex viscosity of carbomer homopolymer type C hydrogels was higher than that of the kappa carrageenan hydrogels. Besides, complex viscosity values were dependent on the secondary polymer present in the formulation. Significant differences among hydrogels were found in detachment force, work of adhesion and spreading diameter results. Association of projective mapping with CATA allowed to determine similarities and dissimilarities among samples. Cluster analysis associated the samples in two groups. Two hydrogels were selected to study the release of caffeine. Both hydrogels presented similar release profiles which were well described by the Higuchi model. Caffeine release was exclusively controlled by a diffusive process. CONCLUSION: Physico-chemical and sensory techniques enabled the identification of bioadhesive hydrogel formulations with positive characteristics for cosmetic applications. Formulations which combined carbomer homopolymer type C with xanthan gum or with carbomer copolymer type B were the most promising for bioadhesive skin products. Caffeine release profiles of selected formulations were not statistically different. Both hydrogels gradually released the active ingredient, reaching approximately 80% within the first 5 h, and their profiles were well described by the Higuchi model. In this context, it could be concluded that the selected hydrogels are suitable bioadhesive hydrogel formulations for cosmetic application on the skin.