EVALUATION OF MUCOADHESIVE PROPERTIES OF HYALURONIC-ACID BENZYL-ESTERS

Mucoadhesive properties of hyaluronic acid (HA) benzyl esters were eva luated. The vertical tensile force of detachment of polymer films from porcine gastric mucosal surface was measured with a microdisplacement transducer. The HA esters, namely, HYAFF 11 p25 (25% benzyl ester, 75 % sodium salt), HYAFF 11 p50 (50% benzyl ester, 50% sodium salt), HYAF F 11 p75 (75% benzyl ester, 25% sodium salt) and HYAFF 11 (100% benzyl ester), were compared to glass (negative control) and to two positive controls, polycarbophil (PC) and hydroxypropylmethylcellulose (HPMC). Measurements were made for polymer films hydrated in a pH 1.2 medium, in Tyrode solution (pH 7.8) and for unhydrated films. When hydrated a t pH 1.2, the more hydrophilic polymers (HPMC, HYAFF 11 p25, HYAFF 11 p50 and PC) showed significantly greater adhesion (2720-4192 dyn/cm(2) ) than the negative control (1980 dyn/cm(2)). When hydrated at pH 7.8, only HPMC (3801 dyn/cm(2)) and HYAFF 11 p25 (3198 dyn/cm(2)) showed g reater adhesion than the negative control. PC adhesion was significant ly lower than at pH 1.2. The ionized state of PC, as well as mucus gly coprotein residues at this pH (7.8), may cause charge repulsion and re duced adhesion. As expected, adhesion of HPMC which is nonionic, was u naffected by pH of the hydration medium. Adhesion of HYAFF 11 p25, and HYAFF 11 p50 was not significantly different at the higher pH. The ad hesion of dry films was greater (4203-6388 dyn/cm(2)) than that of hyd rated films. Adhesion of the dry films may be a result of wetting of t he films and dehydration of the mucous layer by the films. The study o f initial contact time showed a time dependent increase in force of ad hesion after an initial equilibration time. The results indicate poten tial applicability of the hydrophilic HA esters as mucoadhesive polyme rs.