title: Comparative buccal permeability enhancement of didanosine and tenofovir by potential multifunctional polymeric excipients and their effects on porcine buccal histology.
abstract: This study identified and compared the buccal permeability properties of antiretroviral drugs, didanosine (ddI) and tenofovir (TNF), and the permeability effects of polymeric excipients - i.e. carboxymethylcellulose (CMC), sodium alginate (SA), polyacrylic acid (PAA) and polyethylene glycol (PEG) - as potential multifunctional excipients for buccal drug delivery. Permeation studies across porcine buccal mucosa were performed and the drug was quantified using UV spectrophotometry. The mean flux for both ddI (113-181 µg/cm(2)h) and TNF (40-102 µg/cm(2)h) increased linearly with increasing donor concentration. All polymeric excipients improved permeability of TNF while only PEG was effective for ddI. Permeability enhancement ratios at 20 mg/mL for ddI and TNF were 1.63 and 1.74, respectively, using PEG (0.5% w/v) and CMC (0.5% w/v), respectively. The maximum enhancement ratio of 2.13 for TNF was achieved with 4% w/v PEG. Light and transmission electron microscopy revealed no significant loss in cellular integrity of mucosa treated with either TNF or ddI alone or when coupled with PEG as a polymeric enhancer. Histomorphological observations correlated with flux values obtained for TNF and ddI alone, as well as with PEG's effects on drug mass flux. TNF and ddI have demonstrated buccal delivery potential. Selective polymeric excipients provide an effective means to increase their penetration and may serve as potential formulation multifunctional excipients in a delivery system for delivery via the buccal route.
authors: Department of Pharmaceutical Sciences and.
authors: Sanjeev
authors: S
authors: Rambharose
authors: Elizabeth
authors: E
authors: Ojewole
authors: Irene
authors: I
authors: Mackraj
authors: Thirumala
authors: T
authors: Govender
mesh_terms: D000180:Acrylic Resins / Q000494:pharmacology; D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000278:Administration, Buccal; D000464:Alginates / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology; D016049:Didanosine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005079:Excipients / Q000494:pharmacology*; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000494:pharmacology; D013552:Swine; D000068698:Tenofovir
chemical_list: D000180:Acrylic Resins; D000464:Alginates; D019380:Anti-HIV Agents; D005079:Excipients; D006603:Hexuronic Acids; D063065:Organophosphonates; D011092:Polyethylene Glycols; C006903:carbopol 940; D020723:Glucuronic Acid; D000068698:Tenofovir; D000225:Adenine; D016049:Didanosine; D002266:Carboxymethylcellulose Sodium