Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels.
Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti-inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130±11μg/cm(2)h and 108±7μg/cm(2)h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30±4μg/cm(2)h, p<0.05) or solution formulation (44±6μg/cm(2)h, p<0.05) under identical conditions. Over 24h diclofenac transport from the solid hydrogel film was greater than that measured for any new or commercial diclofenac formulation. Entrapment of temperature-responsive nanogels within the solid hydrogel film provides temperature-activated prolonged release of diclofenac. Diclofenac transport was minimal at 22°C, when diclofenac is entrapped within temperature-responsive nanogels incorporated into the solid hydrogel film, but increased 6-fold when the temperature was increased to skin surface temperature of 32°C. These results demonstrate the feasibility of the semisolid gel and solid hydrogel film formulations that can include thermo-responsive nanogels for development of transdermal drug formulations with adjustable drug transport kinetics.
Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, United States.
Carlos A
CA
Carmona-Moran
Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL, United States.
Oleksandra
O
Zavgorodnya
Consultant, Birmingham, AL, United States.
Andrew D
AD
Penman
Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL, United States.
Eugenia
E
Kharlampieva
Department of Medicine, Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, United States.
S Louis
SL
Bridges
Southern Research, Birmingham, AL, United States.
Robert W
RW
Hergenrother
Department of Medicine, Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, United States; Medicine Service, Birmingham VA Medical Center, Birmingham, AL, United States; Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN, United States.
Jasvinder A
JA
Singh
Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, United States. Electronic address: tmwick@uab.edu.
Timothy M
TM
Wick
D000279:Administration, Cutaneous; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D000080385:Nanogels; D010539:Permeability; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry*; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013696:Temperature
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005079:Excipients; D000080385:Nanogels; D011135:Polysaccharides, Bacterial; C413692:polyethylene glycol polyethyleneimine nanogel; D004008:Diclofenac; D011092:Polyethylene Glycols; C048288:gellan gum; D011094:Polyethyleneimine
Diclofenac; Hydrogel film; Nanogels; Semisolid gel; Synthetic membrane; Transdermal drug transport; Transdermal formulation development