Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design

ABSTRACT Formulators face great challenges in adopting systematic approaches for designing self-nanoemulsifying formulations (SNEFs) for different drug categories. In this study, we aimed to build-up an advanced SNEF development framework for weakly basic lipophilic drugs, such as cinnarizine (CN). First, the influence of formulation acidification on CN solubility was investigated. Second, formulation self-emulsification in media with different pH was assessed. Experimentally designed phase diagrams were also utilized for advanced optimization of CN-SNEF. Finally, the optimized formulation was examined using cross polarizing light microscopy for the presence of liquid crystals. CN solubility was significantly enhanced upon external and internal acidification. Among the various fatty acids, oleic acid-based formulations showed superior self-emulsification in all the tested media. Surprisingly, formulation turbidity and droplet size significantly decreased upon equilibration with CN. The design was validated using oleic acid/Imwitor308/Cremophor El (25/25/50), which showed excellent self-nanoemulsification, 43-nm droplet size (for CN-equilibrated formulations), and 88 mg/g CN solubility. In contrast to CN-free formulations, CN-loaded SNEF presented lamellar liquid crystals upon 50% aqueous dilution. These findings confirmed that CN-SNEF efficiency was greatly enhanced upon drug incorporation. The adopted strategy offers fast and accurate development of SNEFs and could be extrapolated for other weakly basic lipophilic drugs

Development of nanotechnology-based drug delivery systems with olive vegetable oil for cutaneous application

ABSTRACT Liquid-Crystalline Systems represent active compounds delivery systems that may be able to overcome the physical barrier of the skin, especially represented by the stratum corneum. To obtain these systems, aqueous and oily components are used with surfactants. Of the different association structures in such systems, the liquid-crystalline offer numerous advantages to a topical product. This manuscript presents the development of liquid-crystalline systems consisting, in which the oil component is olive oil, its rheological characterizations, and the location of liquid crystals in its phase map. Cytotoxic effects were evaluated using J-774 mouse macrophages as the cellular model. A phase diagram to mix three components with different proportions was constructed. Two liquid crystalline areas were found with olive oil in different regions in the ternary diagram with two nonionic surfactants, called SLC1 (S1) and SLC2 (S2). These systems showed lamellar liquid crystals that remained stable during the entire analysis time. The systems were also characterized rheologically with pseudoplastic behavior without thixotropy. The texture and bioadhesion assays showed that formulations were similar statistically (p < 0.05), indicating that the increased amount of water in S2 did not interfere with the bioadhesive properties of the systems. In vitro cytotoxic assays showed that formulations did not present cytotoxicity. Olive oil-based systems may be a promising platform for skin delivery of drugs