smartLipids and smartCrystals for improved dermal delivery of anti-pollution actives

Abstract

Using smartLipids and smartCrystals technology, submicron formulations were developed enabling 4 different anti-pollution strategies: smartLipids 2nd skin provide skin barrier reinforcement, smartLipids 2nd skin Q10 allow improved dermal delivery of the skin-physiological antioxidant Q10. PER smartLipids improve the symptomatic treatment of pollution-induced pigmentation disorders and Symurban smartCrystals provide improved dermal delivery of the aryl hydrocarbon receptor antagonist Symurban. The first aim of this thesis was the development of physically stable smartLipids 2nd skin (Chapter 2). In a surfactant screening 19 out of 16 surfactants lead to immediate aggregation of the formulations. Of the remaining 3 surfactants, only Lanette E proofed to provide long-term stability. After preservation by 3% pentylene glycol, a physical stabilization of the submicron suspension over 1 year could be achieved. The loading test with the model active ingredient coenzyme Q10 showed that the smartLipids 2nd skin could be loaded with up to 50% active ingredient with a storage stability of 11 months. The maximum loading capacity of the NLC formulations published so far (25%) has thus been doubled. Thus, the second aim of this thesis, to demonstrate the high loading capacity of smartLipids, was accomplished. The third aim of this work was the development of physically stable PER smartLipids (Chapter 3). Searching for a suitable lipid, all tested cosmetic oils proofed to have insufficient solubility. Thereupon, so-called "inverse loading method” was developed, i.e. the smartLipids matrix lipid was dissolved in a molten active ingredient. This resulted in a loading of 50% phenylethyl resorcinol, increasing the previously published maximum load in NLC (20%) by factor 2.5. The best result was achieved with Lipocire A, a natural di- and triglyceride mixture, complying the smartLipids properties due to its complex composition. This was used to produce a physically stable suspension for 14 months. In addition, the production process was further developed in this chapter for industrial production-scale. Despite the good chemical stability of PER in smartLipids, a reddish discoloration of the product was observed after several months of storage. This is probably caused by strongly colored degradation products of phenylethyl resorcinol. Therefore, the fourth aim of this thesis was to optimize the color stability of PER smartLipids, which is described in Chapter 4 of this thesis. Tinosorb S and Oxynex ST liquid were the optimal stabilizers, remaining completely without discoloration in both, over 3 months under light protection and in a 7-day light stress test. The physical stability of the PER smartLipids remains unchanged. The verification of the solid state of the PER smartLipids could be carried out in Chapter 5 by differential scanning calorimetry and X-ray diffraction analysis, which was the fifth aim of this thesis. The sixth aim of this thesis was the development of a long-term stable smartCrystals formulation with the aryl hydrocarbon receptor antagonist Symurban (Chapter 6). Wet bead milling proofed to be the most suitable process for the production of smartCrystals. Of the 15 surfactants tested, only Plantacare 810 UP showed sufficient stabilization of the smartCrystals suspension. With this surfactant, physical and chemical stability of the smartCrystals could be achieved for 1 year. The seventh and final aim of this thesis was to demonstrate the performance of Symurban smartCrystals concept. The saturation solubility of the Symurban raw drug powder could be increased almost fifteen fold from 0.2 µg/mL to 2.8 µg/mL by Symurban smartCrystals. In the dermal human case control penetration test, Symurban smartCrystals proofed to transport more than the twice amount of Symurban into deeper skin layers than a conventional cosmetic product. All of the developed formulations provided physical and chemical stability of at least 11 months. Therefore, the overall aim of this thesis as well as all sub-aims could be accomplished.