Influence of additives on a thermosensitive hydrogel for buccal delivery of salbutamol: relation between micellization, gelation, mechanic and release properties.
Thermosensitive hydrogels developed for buccal delivery of salbutamol were prepared using poloxamer analogs (Kolliphor(®) P407/P188), xanthan gum (Satiaxane(®) UCX930) and NaCl. P188 increased gelation temperature (Tsol-gel) by 2.5-5°C, micellization temperature (<1°C) and gelation time by >3s. To obtain a suitable Tsol-gel at 28-34°C, P407 and P188 concentrations were set to 18-19% and 1%. NaCl reduced Tsol-gel (>2°C) out of the optimal range. Six formulations containing 0.05-0.1% Satiaxane(®) fulfilled the temperature criteria. Concerning the gel strength, 1% P188 had no significant effect, NaCl increased it at 20°C, and Satiaxane(®) enhanced it at 20°C and 37°C. The release study using membrane-less (to mimic oral cavity) and membrane (to mimic buccal mucosa side) methods allowed a complete investigation showing that erosion and diffusion both contributed to the drug release but differed according to the formulation. In the membraneless method, simple P407 formulations had weak ability to retain salbutamol (T80=35 min). P188 accelerated drug release. NaCl accelerated release in the membraneless method by 5-11 min but slightly reduced it in the membrane method. The hydrogels containing Satiaxane(®) exhibited the slowest release. In the membrane method, combination of P407/P188/Satiaxane(®) provided a sustained diffusion with a burst effect (T25=9.6 min, T80=97.8 min), which provides potential clinical interests.
CNRS UMR 8258 (ex 8151) - Inserm U1022, Paris Descartes University, Paris F-75006, France; Unither Développement Bordeaux, Le Haillan F-33185, France.
Ni
N
Zeng
CNRS UMR 8258 (ex 8151) - Inserm U1022, Paris Descartes University, Paris F-75006, France.
Gilles
G
Dumortier
Unither Développement Bordeaux, Le Haillan F-33185, France.
Marc
M
Maury
CNRS UMR 8258 (ex 8151) - Inserm U1022, Paris Descartes University, Paris F-75006, France.
Nathalie
N
Mignet
CNRS UMR 8258 (ex 8151) - Inserm U1022, Paris Descartes University, Paris F-75006, France; Mise au point galénique, Agence Générale des Equipements et des Produits de Santé (AGEPS), AP-HP, Paris F-75005, France. Electronic address: vincent.boudy@eps.aphp.fr.
Vincent
V
Boudy
D000268:Adhesiveness; D000278:Administration, Buccal; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D004337:Drug Carriers; D020100:Hydrogels; D007700:Kinetics; D008567:Membranes, Artificial; D008823:Micelles; D008956:Models, Chemical; D020442:Poloxamer / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013718:Tensile Strength; D014783:Viscosity
D004337:Drug Carriers; D020100:Hydrogels; D008567:Membranes, Artificial; D008823:Micelles; D011135:Polysaccharides, Bacterial; D020442:Poloxamer; D012965:Sodium Chloride; D000420:Albuterol; C002563:xanthan gum
Drug release; Flow through cell (USP 4 apparatus); Mathematical modeling; NaCl; Poloxamer; Xanthan gum