In vitro and in vivo characteristics of a thermogelling and bioadhesive delivery system intended for rectal administration of quinine in children.
The aim of this work was to improve the rectal bioavailability of quinine hydrochloride by designing thermosensitive and mucoadhesive gels intended for rectal delivery. The rheological and mucoadhesive properties of poloxamer 407 solutions have been modulated by addition of hydroxypropylmethycellulose (HPMC) and propanediol-1,2. In vitro release and rectal absorption of quinine have been highlighted by a dialysis dissolution testing method and by the determination of bioavailability of the different formulations in rabbits. Increasing the proportions of HPMC and poloxamer in the formulations resulted in a prolonged release of quinine. Indeed, compared to the DT 50% of a rectal solution and a simple HPMC gel (27 and 65 min, respectively) the DT 50% of thermosensitive ternary systems was increased and ranged between 80 and 138 min, depending on the system composition. The release rate depended strongly on the elasticity of the gels after thermogelation. The absolute rectal bioavailability of quinine determined in rabbits was significantly improved with these thermosensitive and adhesive systems. It increased from 62% for the rectal solution to 98% for a ternary system 16/0.5/30 (poloxamer (16%)/HPMC (0.5%)/propanediol-1,2 (30%)). As a result of combined bioadhesion and prolonged release of quinine in vivo, higher average values of MRT and t(max) (9.1+/-0.2h and 30 min, respectively) were obtained compared to the rectal solution (6.9+/-0.9h and 15 min, respectively). Moreover, these formulations presented a very good rectal tolerance. Modulation by HPMC of the viscoelastic and mucoadhesive properties of poloxamer 407 thermogelling solutions allowed a prolonged release of quinine hydrochloride and an improvement of bioavailability in rabbit.
Koffi
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AA
Laboratoire de Biopharmacie et de Technologie Pharmaceutique, UFR des Sciences Pharmaceutiques et Biologiques d'Abidjan, Cote d'Ivoire. paularmandkoffi@yahoo.fr <paularmandkoffi@yahoo.fr>
Agnely
F
F
Besnard
M
M
Kablan Brou
J
J
Grossiord
J L
JL
Ponchel
G
G
D000285:Administration, Rectal; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods; D002648:Child; D016503:Drug Delivery Systems; D006358:Hot Temperature; D006801:Humans; D065347:Hypromellose Derivatives; D066298:In Vitro Techniques; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D011803:Quinine / Q000008:administration & dosage*; D011817:Rabbits
D000962:Antimalarials; D001672:Biocompatible Materials; D065347:Hypromellose Derivatives; D019946:Propylene Glycol; D008747:Methylcellulose; D011803:Quinine