title: Rheological and mucoadhesive characterization of polymeric systems composed of poly(methylvinylether-co-maleic anhydride) and poly(vinylpyrrolidone), designed as platforms for topical drug delivery.
abstract: This study examined the rheological and mucoadhesive properties of polymeric systems composed of the bioadhesive copolymer poly(methylvinylether-co-maleic anhydride), PMVE/MA and poly(vinylpyrrolidone, PVP) as candidate platforms for improved drug delivery to the oral cavity. Aqueous, neutral formulations were prepared containing PMVE/MA (10 or 15% w/w) and PVP (0-9% w/w). The rheological properties were examined at 20 +/- 0.1 degrees C using both oscillatory rheometry (0.01 to 1.0 Hz at a constant strain of 1.0 x 10(-3) rad) and controlled stress flow rheometry using a Carri-Med CSL(2)-100 rheometer. The mechanical properties were examined using texture profile analysis (15-mm depth of insertion, 9 mm s(-1) rate of insertion, 15 s delay period between the end of the first and beginning of the second compressions). The interaction of the various formulations with mucin was examined using oscillatory rheometry. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing the concentration of each polymeric component increased the zero-rate viscosity (calculated using the Cross model), hardness, compressibility, the storage (G') and loss (G") moduli, and decreased the loss tangent. These observations may be due to greater polymeric entanglement between adjacent polymer chains. Specifically, rheological synergy was observed between PMVE/MA and PVP, evidence of complexation between these two polymers. From the relationship between the viscoelastic properties and oscillatory frequency, and the mathematical comparison of steady and oscillatory shear response of formulations using the Cox-Merz equation, it may be concluded that formulations containing 15% w/w PMVE/MA and either 6 or 9% w/w PVP exhibited rheological properties that were consistent with gel behavior. All other formulations exhibited rheological properties that resembled polymeric liquids. Increasing the concentrations of PMVE/MA and PVP significantly increased the interaction with mucin, the rheological synergy between the polymeric formulations and mucin and, in addition, the adhesiveness of the formulations. This is evidence of the muco/bioadhesive properties of the formulations. Conversely, the time of contact between each formulation and mucin did not affect their resultant interaction. In conclusion, this study has uniquely described the rheological and mucoadhesive properties of aqueous systems composed of PMVE/MA and PVP. In particular, the concentrations required for gel formation have been defined and the interaction between these two polymeric components illustrated using rheological methods. Furthermore, the simultaneous analysis of rheological, mechanical, and mucoadhesive data provided an insight into their potential utility as platforms for drug delivery systems for application to the oral cavity.
authors.affiliation: School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, United Kingdom. d.jones@qub.ac.uk
authors.forename: David S
authors.initials: DS
authors.lastname: Jones
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Lawlor
authors.forename: A David
authors.initials: AD
authors.lastname: Woolfson
mesh_terms: D000269:Adhesives; D000287:Administration, Topical; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004344:Drug Incompatibility; D005782:Gels; D008298:Maleates / Q000737:chemistry*; D009077:Mucins / Q000737:chemistry*; D010592:Pharmaceutic Aids / Q000737:chemistry; D011095:Polyethylenes / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012212:Rheology
chemical_list: D000269:Adhesives; D005782:Gels; D008298:Maleates; D009077:Mucins; D010592:Pharmaceutic Aids; D011095:Polyethylenes; C043105:poly(methyl vinyl ether-co-maleic anhydride); D011205:Povidone