RESUMO
BACKGROUND: Propranolol (PPN) is a therapeutic option for the treatment of infantile hemangiomas. This study aimed at the development of nanoemulsion (NE) containing 1% PPN, characterization of the system, and safety studies based on ex vivo permeation, cytotoxicity, and biodistribution in vivo. METHODS: The formulation was developed and characterized in relation to the droplet size, polydispersity index (PDI), pH, zeta potential, and electronic microscopy. Ex vivo permeation studies were used to evaluate the cutaneous retention of PPN in the epidermis and dermis. Cytotoxicity studies were performed in fibroblasts, macrophages, and keratinocytes. In vivo biodistribution assay of the formulations was performed by means of labeling with technetium-99m. RESULTS: NE1 exhibited droplet size of 26 nm, PDI <0.4, pH compatible with the skin, and zeta potential of -20 mV, which possibly contributes to the stability. Electron microscopy showed that the NE presented droplets of nanometric size and spherical shape. NE1 provided excellent stability for PPN. In the ex vivo cutaneous permeation assay, the NE provided satisfactory PPN retention particularly in the dermis, which is the site of drug action. In addition, NE1 promoted cutaneous permeation of the PPN in small amount. In vivo biodistribution showed that the radiolabeled formulation remained in the skin and a small amount reached the bloodstream. NE1 presented low cytotoxicity to fibroblasts, macrophages, and keratinocytes in the concentrations evaluated in the cytotoxicity assay. CONCLUSION: We concluded that the formulation is safe for skin administration; however, cutaneous irritation studies should be performed to confirm the safety of the formulation before clinical studies in patients with infantile hemangiomas.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Emulsões/administração & dosagem , Nanoestruturas/administração & dosagem , Propranolol/administração & dosagem , Pele/efeitos dos fármacos , Administração Cutânea , Administração Tópica , Animais , Células Cultivadas , Emulsões/química , Emulsões/farmacocinética , Epiderme/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Masculino , Nanoestruturas/química , Propranolol/farmacocinética , Ratos Wistar , Pele/citologia , Absorção Cutânea , Sus scrofa , Tecnécio , Distribuição TecidualRESUMO
This paper reports the development, characterization and
O trabalho reporta o desenvolvimento, caracterização e estudo
Assuntos
Humanos , Química Farmacêutica , Sulfassalazina/administração & dosagem , Sulfassalazina/farmacocinética , Sulfassalazina/farmacologia , Sistemas de Liberação de Medicamentos , Gastroenterite/tratamento farmacológicoRESUMO
The purpose of this study was to propose an analytical procedure that provides the effects of particle size and surface area on dissolution of efavirenz. Five different batches obtained by different micronization processes and with different particle size distribution and surface area were studied. The preformulation studies and dissolution curves were used to confirm the particle size distribution effect on drug solubility. No polymorphic variety or amorphization was observed in the tested batches and the particle size distribution was determined as directly responsible for the improvement of drug dissolution. The influence of the preparation process on the tablets derived from efavirenz was observed in the final dissolution result in which agglomeration, usually seen in non-lipophilic micronized material, was avoided through the use of an appropriate wet granulation method. For these reasons, micronization may represent one viable alternative for the formulation of brick dust drugs.