Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan.
Rapid mucociliary clearance of intranasally administered drugs is often a key factor in determining the bioavailability of such therapeutic agents. The use of mucoadhesive microparticles provide a potential strategy for improving retention of drugs within the nasal cavity, and thereby improve the resultant pharmacokinetic profile. This study describes the comparison of a number of novel, potentially mucoadhesive microspheres, prepared by solvent evaporation, composed of hyaluronic acid (HA), chitosan glutamate (CH) and a combination of the two with microcapsules of HA and gelatin prepared by complex coacervation. The microspheres had a mean particle size of 19.91+/-1.57 microm (HA), 28.60+/-1.34 microm (HA/CH), 29.47+/-3.58 microm (CH). The incorporation of a model drug, gentamicin sulphate (%) was 46.90+/-0.53 (HA), 28.04+/-1.21 (HA/CH) and 13.32+/-1.04 (CH). The in vitro release profiles of microsphere formulations prepared by solvent evaporation were determined. The release of gentamicin from HA and HA/CH was 50% longer than CH and was best modelled as a release from a matrix. The degree of mucoadhesion of each formulation was investigated by determining the mucociliary transport rate (MTR) of the microparticles across an isolated frog palate. Acacia/gelatin microcapsules were used as a positive control. The rank order of mucoadhesion for the microspheres and the microparticles was HA=HA/CH>CH>HA/gelatin>CHins. The entrapment of gentamicin did not affect the mucoadhesive properties (P>0.05, Mann--Whitney U-test). The combination of HA with chitosan may afford additional advantages in combining the mucoadhesive potential of HA with the penetration enhancing effect of chitosan.
Lim
S T
ST
Medicines Research Development Centre, Department of Pharmacy, King's College London, 150 Stamford Street, London, UK.
Martin
G P
GP
Berry
D J
DJ
Brown
M B
MB
D000045:Acacia; D002686:Chitin / Q000031:analogs & derivatives*; D048271:Chitosan; D016503:Drug Delivery Systems; D005454:Fluorescence Polarization; D005780:Gelatin; D005839:Gentamicins / Q000493:pharmacokinetics; D006820:Hyaluronic Acid; D066298:In Vitro Techniques; D008863:Microspheres; D008962:Models, Theoretical; D009092:Mucous Membrane / Q000378:metabolism
D005839:Gentamicins; D002686:Chitin; D005780:Gelatin; D006820:Hyaluronic Acid; D048271:Chitosan