Formulation of mucoadhesive vaginal hydrogels insensitive to dilution with vaginal fluids

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• 作者：Armelle Aka-Any-Grah ; Kawthar Bouchemal ; Arm ; Koffi ; Florence Agnely ; Min Zhang ; Madeleine Djabourov ; Gilles Ponchel
• 关键词：Thermogelling system ; Vaginal hydrogels ; Mucoadhesion ; Pluronic
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2010
• 出版时间：October 2010
• 年：2010
• 卷：76
• 期：2
• 页码：296-303
• 全文大小：528 K

文摘

The main objective of this work was to design thermosensitive and mucoadhesive vaginal hydrogels able to keep their rheological and mucoadhesive properties after dilution with vaginal fluids. Formulations were composed of pluronic F127 or a mix of two pluronics F127 and F68. Both formulations contained hydroxypropylmethyl cellulose (HPMC) as a mucoadhesive polymer. The determination of gelling temperature (T_gel) after dilution with simulated vaginal fluid (SVF) demonstrated that hydrogels were resistant to dilution and T_gel values were close to 30 °C. Ex vivo mucoadhesion experiments conducted on porcine vaginal mucosa founded on the technique of traction of the adhesive/adherent joint allowed the characterization of mucoadhesive properties of hydrogels by measuring work of adhesion (W) and maximum force of detachment (F_max). In the case of F127-based hydrogels, W and F_max were lowered after dilution with SVF. However, in the case of F127/F68-based hydrogels, W, F_max and mucoadhesion profiles were weakly affected by dilution. These differences could be attributed to the higher elasticity of F127/F68/HPMC (22.5/2.5/1 % w/w) hydrogel in comparison with F127/HPMC one (20/1 % w/w). Indeed, rheological analyses of the formulations showed that both elastic (G′) and viscous moduli (G′′) were higher for F127/F68/HPMC (22.5/2.5/1 % w/w) than for F127/HPMC hydrogel (20/1 % w/w). However, we demonstrated that the higher elasticity of the hydrogel was due to the higher total pluronic concentration and not due to the presence of F68 in the formulation.