Modulation of the rheological and mucoadhesive properties of thermosensitive poloxamer-based hydrogels intended for the rectal administration of quinine.
The aim of this work was to formulate and characterize thermosensitive gels based on poloxamer 407, a thermosensitive polymer, and hydroxypropylmethylcellulose (HPMC), a bioadhesive polymer, intended for the rectal delivery of quinine in children. In order to avoid the macroscopic phase separation between the two polymers it was necessary to add propanediol-1,2. After the formulation of stable ternary systems, their rheological properties were studied as a function of temperature. It was thus possible to obtained the gelation temperature of the systems as well as their elastic modulus, G', at 37 degrees C. It appeared that HPMC in the presence of propanediol-1,2 had a synergistic effect on the gelation of poloxamer 407. Tests on the rabbit rectal mucous membrane, founded on a technique of traction of the adhesive/adhered joint, made it possible to characterize the bioadhesive properties of the gels by measuring the work of adhesion, W, and the maximum detachment force, F(max). Over small concentration ranges of poloxamer and HPMC, very important variations of the viscoelastic and mucoadhesives properties were observed. It was shown that the viscoelastic and the bioadhesive properties were tightly correlated. Indeed, an empirical equivalence relation was established between the shear frequency and the rate of deformation in traction and allowed to describe all our samples by a master curve. This master curve would make it possible to predict the values of W at various rates of traction by the simple non-destructive measurement of the elastic modulus, G', at an equivalent shear frequency.
Koffi
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AA
Laboratory of Biopharmacy and Pharmaceutical Technology, UFR of Pharmaceutical Sciences of Abidjan, 01 BP V 34 Abidjan 01, Côte d'Ivoire, Telex 26138, France. paularmandkoffi@yahoo.fr
Agnely
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F
Ponchel
G
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Grossiord
J L
JL
D000268:Adhesiveness; D000285:Administration, Rectal; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D004548:Elasticity; D020100:Hydrogels / Q000737:chemistry*; D065347:Hypromellose Derivatives; D066298:In Vitro Techniques; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D009092:Mucous Membrane / Q000737:chemistry / Q000378:metabolism; D020442:Poloxamer / Q000737:chemistry*; D011803:Quinine / Q000008:administration & dosage*; D011817:Rabbits; D012212:Rheology; D013696:Temperature; D014014:Tissue Adhesives / Q000737:chemistry*; D014783:Viscosity
D000962:Antimalarials; D003692:Delayed-Action Preparations; D020100:Hydrogels; D014014:Tissue Adhesives; D020442:Poloxamer; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D011803:Quinine