Release of naltrexone on buccal mucosa: permeation studies, histological aspects and matrix system design.
Transbuccal drug delivery has got several well-known advantages especially with respect to peroral way. Since a major limitation in buccal drug delivery could be the low permeability of the epithelium, the aptitude of NLX to penetrate the mucosal barrier was assessed. Ex vivo permeation across porcine buccal mucosa 800 microm thick was investigated using Franz type diffusion cells and compared with in vitro data previously obtained by reconstituted human oral epithelium 100 microm thick. Both fluxes (Js) and permeability coefficients (K(p)) are in accordance, using either buffer solution simulating saliva or natural human saliva. Permeation was evaluated also in presence of chemical enhancers or iontophoresis. No significant differences in penetration rate were observed using chemical enhancers; in contrast, Js and K(p) were extensively affected by application of electric fields. Tablets, designed for Naltrexone hydrochloride (NLX) administration on buccal mucosa, were developed and prepared by direct compression of drug loaded (56%) poly-octylcyanocrylate (poly-OCA) matrices. NLX is slowly discharged from buccal tablets following Higuchian kinetic. Histologically, no signs of flogosis ascribable to NLX and/or poly-OCA were observed, while cytoarchitectural changes due to iontophoresis were detected. Buccal tablets containing NLX may represent a potential alternative dosage form in addiction management.
Giannola
Libero Italo
LI
Dipartimento di Chimica e Tecnologie Farmaceutiche, Università di Palermo, Palermo, Italy. litagian@unipa.it
De Caro
Viviana
V
Giandalia
Giulia
G
Siragusa
Maria Gabriella
MG
Tripodo
Claudio
C
Florena
Ada Maria
AM
Campisi
Giuseppina
G
D000278:Administration, Buccal; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000379:methods; D005557:Formaldehyde / Q000737:chemistry; D007478:Iontophoresis; D007700:Kinetics; D009061:Mouth Mucosa / Q000187:drug effects*; D009271:Naltrexone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013055:Spectrophotometry, Infrared; D013552:Swine; D013607:Tablets; D013997:Time Factors
D009292:Narcotic Antagonists; D013607:Tablets; D005557:Formaldehyde; D009271:Naltrexone