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Influence of additives on a thermosensitive hydrogel for buccal delivery of salbutamol: Relation between micellization, gelation, mechanic and release properties

Abstract : Thermosensitive hydrogels developed for buccal delivery of salbutamol were prepared using poloxamer analogs ( Kolliphor (R) P407/P188), xanthan gum (Satiaxane (R) UCX930) and NaCl. P188 increased gelation temperature (Tsol-gel) by 2.5-5 degrees C, micellization temperature (<1 degrees C) and gelation time by >3s. To obtain a suitable Tsol-gel at 28-34 degrees C, P407 and P188 concentrations were set to 18-19% and 1%. NaCl reduced Tsol-gel (>2 degrees C) out of the optimal range. Six formulations containing 0.05-0.1% Satiaxane (R) fulfilled the temperature criteria. Concerning the gel strength, 1% P188 had no significant effect, NaCl increased it at 20 degrees C, and Satiaxane (R) enhanced it at 20 degrees C and 37 degrees 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 (T-80 = 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 (R) exhibited the slowest release. In the membrane method, combination of P407/P188/Satiaxane (R) provided a sustained diffusion with a burst effect (T-25 = 9.6 min, T-80 = 97.8 min), which provides potential clinical interests. (c) 2014 Published by Elsevier B. V.
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Submitted on : Monday, July 19, 2021 - 1:41:07 PM
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Ni Zeng, Gilles Dumortier, Marc Maury, Nathalie Mignet, Vincent Boudy. Influence of additives on a thermosensitive hydrogel for buccal delivery of salbutamol: Relation between micellization, gelation, mechanic and release properties. International Journal of Pharmaceutics, Elsevier, 2014, 467 (1-2), pp.70-83. ⟨10.1016/j.ijpharm.2014.03.055⟩. ⟨hal-03290560⟩

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