Developing Transdermal Applications of Ketorolac Tromethamine Entrapped in Stimuli Sensitive Block Copolymer Hydrogels

• DOI: 10.1007/s11095-017-2181-8
• Publication Date: 2017-05-24T17:25:59Z
• Authors: Mireia Mallandrich; Francisco Fernánd...; Beatriz Clares; Lyda Halbaut; Cristina Alonso; Luisa Coderch; Maria L. Garduño-...; Berenice Andrade; Alfonso del Pozo; Majella E. Lane; Ana C. Calpena
• Keywords: Adult; Farmacologia; carbomer; Skin Absorption; ketorolac; Biological Availability; Medicació transdèrmica; Poloxamer; Pharmaceutical technology; Administration, Cutaneous; Models, Biological; Permeability; Ketorolac Tromethamine; Excipients; Young Adult; Mice; 03 medical and health sciences; Antiinflammatory agents; Animals; Humans; Fórmules magistrals; Tissue Distribution; Administration of drugs; hydrogels; Reologia; Pharmacology; 0303 health sciences; Viscosity; Anti-Inflammatory Agents, Non-Steroidal; Agents antiinflamatoris; Hydrogels; Hydrogen-Ion Concentration; Middle Aged; Transdermal medication; tromethamine; Medical formularies; 3. Good health; ketorolac tromethamine; transdermal; Female; Administració de medicaments; Rheology; poloxamer; Porosity; Tecnologia farmacèutica

In order to obtain dermal vehicles of ketorolac tromethamine (KT) for the local treatment of inflammation and restrict undesirable side effects of systemic levels hydrogels (HGs) of poloxamer and carbomer were developed.KT poloxamer based HG (KT-P407-HG) and KT carbomer based HG (KT-C940-HG) were elaborated and characterized in terms of swelling, degradation, porosity, rheology, stability, in vitro release, ex vivo permeation and distribution skin layers. Finally, in vivo anti-inflammatory efficacy and skin tolerance were also assessed.HGs were transparent and kept stable after 3 months exhibiting biocompatible near neutral pH values. Rheological patterns fitted to Herschel-Bulkley for KT-C940-HG and Newton for KT-P407-HG due to its low viscosity at 25°C. Rapid release profiles were observed through first order kinetics. Following the surface the highest concentration of KT from C940-HG was found in the epidermis and the stratum corneum for P407-HG. Relevant anti-inflammatory efficacy of KT-P407-HG revealed enough ability to provide sufficient bioavailability KT to reach easily the site of action. The application of developed formulations in volunteers did not induce any visual skin irritation.KT-P407-HG was proposed as suitable formulation for anti-inflammatory local treatment without theoretical systemic side effect.