TitleTransdermal and transbuccal drug delivery
NameHu, Longsheng (author), Michniak-Kohn, Bozena (chair), Minko, Tamara (internal member), You, Guofeng (internal member), Dayan, Nava (outside member), Rutgers University, Graduate School - New Brunswick,
Drug delivery systems,
DescriptionTransdermal and transbuccal routes offer attractive alternatives for systemic delivery of drugs due to their distinct advantages: non-invasive, avoidance of first-pass effect, improved bioavailability and reduction of systemic side effects. However, only a few drugs have been successfully delivered into blood stream to reach therapeutic levels without causing notable skin irritation or damage. Transbuccal drug delivery systems are still at research stage. The major barriers to transdermal and transbuccal drug delivery are stratum corneum of skin and epithelium of buccal tissue. The objective of this work was to overcome these barriers to significantly enhance transdermal and transbuccal delivery of hydrophilic drugs without causing major damage to skin and buccal tissue. In this work, iontophoresis, chemical enhancers and their combination were investigated for their enhancement effects on transdermal and transbuccal delivery of hydrophilic drugs with different indications: lidocaine HCl (LHCl) for pain management, nicotine hydrogen tartrate (NHT) for smoking cessation, diltiazem HCl (DHCl) for anti-hypertension and ondansetron HCl (ODAN HCl) for anti-vomiting. Low toxic chemical enhancers used were dodecyl 2-(N, N-dimethyl amino) propionate (DDAIP), its HCl salt dodecyl-2-(N, N-dimethylamino) propionate hydrochloride (DDAIP HCl), N-(4-bromobenzoyl)-S,S-dimethyliminosulfurane (Br-iminosulfurane). Their enhancement effects were evaluated using in vitro Franz cell diffusion model via porcine skin and buccal tissue. The results demonstrated that iontophoresis alone significantly enhanced transdermal and transbuccal delivery of LHCl, NHT, DHCl and ODAN HCl. DDAIP HCl alone significantly enhanced transbuccal delivery of these four drugs. DDAIP and Br-iminosulfurane significantly enhanced transdermal delivery of LHCl and ODAN HCl. Synergistic enhancement effects were observed on transdermal delivery of LHCl and NHT, ODAN HCl when using DDAIP or Br-iminosulfurane in combination with iontophoresis. A light microscopy, DSC and SEM studies showed that treatment with chemical enhancers and iontophoresis did not cause major morphological changes in the skin and buccal tissue. EpiOral™ MTS cytotoxicity study demonstrated that DDAIP HCl at less than 5% (w/v) in water did not have significant detrimental effects on buccal tissue. In conclusions, iontophoresis and chemical enhancer and their combined treatment are feasible approaches to enhance transdermal and transbuccal delivery of LHCl, NHT, DHCl and ODAN HCl.
NoteIncludes bibliographical references
Noteby Lonsheng Hu
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.