Formulation Development and Characterization of Nanoemulsion-Based Formulation for Topical Delivery of Heparinoid

Heparinoid is commonly used for the treatment of superficial thrombophlebitis, a condition wherein inflammation and clotting occurs in the veins below the skin surface. However, stratum corneum is a major barrier that limits the delivery of hydrophilic heparinoid, in and across the skin. The aim of the present study was to develop a nonirritant topical formulation for heparinoid incorporating chemical penetration enhancers and investigate the delivery of heparinoid across the human epidermis using in vitro vertical Franz diffusion cells. The developed oil-in-water nanoemulsions (NEs; NE-1 and NE-2) delivered higher amount of heparinoid (91.58 +/- 25.75 mu g/sq.cm and 62.67 +/- 5.66 mu g/sq.cm, respectively) after 72 h compared with the other developed formulations, which in turn also delivered significantly higher amount compared with commercial formulations: cream (1.78 +/- 0.07 mu g/sq.cm), ointment (9.95 +/- 4.41 mu g/sq.cm), and gel (0 mu g/sq. cm) (p < 0.05). Transmission electron microscopy, polarizing light microscopy, and dynamic light scattering studies were performed to characterize the microstructure of these NEs with chemical enhancers. NE-1 was tested to be nonirritant with cell viability greater than 50% and a minimal release of IL-1 alpha by using the in vitro Epiderm tissue model. Our results demonstrate that NE formulations represent a potential strategy for providing a localized therapy for the treatment of superficial thrombophlebitis. (c) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.