Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity.
This study described the formulation and characterisation of the viscoelastic, mechanical and mucoadhesive properties of thermoresponsive, binary polymeric systems composed of poloxamer (P407) and poly(acrylic acid, C974P) that were designed for use as a drug delivery platform within the oral cavity. Monopolymeric and binary polymeric formulations were prepared containing 10, 15 and 20% (w/w) poloxamer (407) and 0.10-0.25% (w/w) poly(acrylic acid, 934P). The flow rheological and viscoelastic properties of the formulations were determined using controlled stress and oscillatory rheometry, respectively, the latter as a function of temperature. The mechanical and mucoadhesive properties (namely the force required to break the bond between the formulation and a pre-hydrated mucin disc) were determined using compression and tensile analysis, respectively. Binary systems composed of 10% (w/w) P407 and C934P were elastoviscous, were easily deformed under stress and did not exhibit mucoadhesion. Formulations containing 15 or 20% (w/w) Pluronic P407 and C934P exhibited a sol-gel temperature T(sol/gel), were viscoelastic and offered high elasticity and resistance to deformation at 37 degrees C. Conversely these formulations were elastoviscous and easily deformed at temperatures below the sol-gel transition temperature. The sol-gel transition temperatures of systems containing 15% (w/w) P407 were unaffected by the presence of C934P; however, increasing the concentration of C934P decreased the T(sol/gel) in formulations containing 20% (w/w) P407. Rheological synergy between P407 and C934P at 37 degrees C was observed and was accredited to secondary interactions between these polymers, in addition to hydrophobic interactions between P407 micelles. Importantly, formulations composed of 20% (w/w) P407 and C934P exhibited pronounced mucoadhesive properties. The ease of administration (below the T(sol/gel)) in conjunction with the viscoelastic (notably high elasticity) and mucoadhesive properties (at body temperature) render the formulations composed of 20% (w/w) P407 and C934P as potentially useful platforms for mucoadhesive, controlled topical drug delivery within the oral cavity.
School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, Northern Ireland, United Kingdom. d.jones@qub.ac.uk
David S
DS
Jones
Marcos Luciano
ML
Bruschi
Osvaldo
O
de Freitas
Maria Palmira Daflon
MP
Gremião
Elza Helena Guimarães
EH
Lara
Gavin P
GP
Andrews
D000179:Acrylates / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D001696:Biomechanical Phenomena; D015195:Drug Design; D015918:Infusion Pumps, Implantable; D009055:Mouth / Q000187:drug effects / Q000378:metabolism; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism; D020442:Poloxamer / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D012212:Rheology; D014014:Tissue Adhesives / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism
D000179:Acrylates; D014014:Tissue Adhesives; C117167:carbopol 974P NF; D020442:Poloxamer