RESUMEN
Levocetirizine dihydrochloride active ingredient was microencapsulated using nano spray-drying technology for preparing microparticles containing topical gel against edema. Hydroxyl propyl methyl cellulose (HPMC) was used as a carrier polymer during spray drying. The active ingredient content of the nano spray-dried products was 52.81% (w/w) and 51.33% (w/w) for ex vivo and in vivo experiments, respectively, and the average particle size was 2.6 µm. X-ray diffraction analysis indicated an amorphous state of the active ingredient embedded in the amorphous matrix of the polymer. Dermal oil gels composed of Miglyol 812 gelated by Dermofeel viscolid included 5% (w/w) (for ex vivo) and 10% (w/w) (for in vivo) active ingredient without or with 0.05% (w/w) menthol penetration enhancer. Qualitative ex vivo penetration studies using a confocal Raman microscopic correlation mapping were executed on human abdominal skin. The results showed that the active ingredient was enriched in the epidermis and upper dermis layer of the skin using oleogel loaded with the nano spray-dried drug-HPMC composite. Menthol addition to the oleogel resulted in the concentration of levocetirizine in the dermis. In vivo tests were performed on a mouse model of croton oil-induced ear edema. Negative control and Fenistil-treated groups were compared using the prepared oil gels with and without menthol. Without penetration enhancer, 20 µL of our oil gel loaded with nano spray-dried levocetirizine dihydrochloride composite showed similar effectiveness to the same volume of Fenistil gel, while 5 µL menthol containing sample was sufficient to eliminate the skin irritation similarly to 20 µL Fenistil.
RESUMEN
Dermal foams are promising drug delivery systems due to their many advantages and ease of application. Foams are also considered a novelty in the field of dermatology. In particular, they are beneficial for the treatment of skin conditions where patients have highly inflamed, swollen, infected and sensitive skin, as the application of the foam to the skin surface to be treated minimizes the need for skin contact. In order to formulate foams, it is necessary to know which material and process parameters influence the quality characteristics of foams and which methods can be used to study foams; this part of the research is assisted by the QbD approach. By using the QbD concept, it contributed during the development process to ensure quality-based development. With initial risk assessment, the critical material attributes (CMAs) and the critical process parameters (CPPs) were identified to ensure the required critical quality attributes (CQAs). During the initial risk assessment, five high-risk CQAs, namely foam volume stability, foam expansion, cross point, the initial values of the number and size of bubbles, and three medium-risk CQAs, namely spreadability, relative foam density and viscosity of the liquid system were identified and investigated. In this research, different types of polymers (xanthan gum, hydroxyethylcellulose, different types of hyaluronic acids) were used to improve the properties of foam formulations. The formulations containing xanthan gum and high molecular weight hyaluronic acid had good foam properties and will be appropriate delivery systems for an active pharmaceutical ingredient. Overall, the polymer content had a great effect on the properties of the foams. Different polymers affect the properties of foams in different ways. When used in combination, the methods reinforce each other and help to select a formula for dermal application.
