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

• Published in: Pharmaceutical research Vol. 34; no. 8; pp. 1728 - 1740
• Main Authors: Mallandrich, Mireia, Fernández-Campos, Francisco, Clares, Beatriz, Halbaut, Lyda, Alonso, Cristina, Coderch, Luisa, Garduño-Ramírez, Maria L., Andrade, Berenice, del Pozo, Alfonso, Lane, Majella E., Calpena, Ana C.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-08-2017; Springer; Springer Nature B.V; Springer Science + Business Media
• Subjects: Administració de medicaments; Administration of drugs; Administration, Cutaneous; Adult; Agents antiinflamatoris; Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antiinflammatory agents; Bioavailability; Biochemistry; Biological Availability; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Block copolymers; Degradation; Epidermis; Excipients; Farmacologia; Female; Formulations; Fórmules magistrals; Humans; Hydrogels; Hydrogen-Ion Concentration; Inflammation; Irritation; Ketorolac; Ketorolac Tromethamine - chemistry; Ketorolac Tromethamine - pharmacology; Kinetics; Medicació transdèrmica; Medical formularies; Medical Law; Mice; Middle Aged; Models, Biological; Permeability; pH effects; Pharmaceutical technology; Pharmacology; Pharmacology/Toxicology; Pharmacy; Poloxamer - chemistry; Polyacrylic acid; Porosity; Reologia; Research Paper; Rheological properties; Rheology; Side effects; Skin; Skin Absorption; Stratum corneum; Tecnologia farmacèutica; Tissue Distribution; Transdermal medication; Tromethamine; Viscosity; Young Adult; poloxamer; hydrogels; ketorolac tromethamine; carbomer; transdermal
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-017-2181-8

Purpose
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.
Methods
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.
Results
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.
Conclusions
KT-P407-HG was proposed as suitable formulation for anti-inflammatory local treatment without theoretical systemic side effect.