Examination of aqueous oxidized cellulose dispersions as a potential drug carrier. II. In vitro and in vivo evaluation of phenylpropanolamine release from microparticles and pellets.

The purpose of this research is to investigate the release of phenylpropanolamine from oxidized cellulose-phenylpropanolamine (OC-PPA) complexes prepared using aqueous OC dispersions (degree of neutralization, DN, 0-0.44) and phenylpropanolamine-hydrochloride (PPA.HCl) (concentration, 0.5 M or 1.4 M) in vitro and in vivo. The results showed a faster drug release from the OC-PPA complex made using the OC dispersion with a DN value of 0.22 than from those prepared using dispersions with DN values of 0.29 to 0.44. No significant difference existed between the release profiles of OC-PPA microparticles made using OC dispersions with DN values of 0.29 to 0.44. OC-PPA complexes that contained smaller size particles or higher drug levels, or that were processed by freeze drying released PPA faster. Compared with microparticles, the pellets of OC-PPA complexes released PPA more slowly initially. An increase in pH or ionic strength of the dissolution medium increased the release of PPA, which is attributable to increased polymer hydration and solubilization at higher pH and ionic strength conditions. The OC-PPA pellets implanted subcutaneously in rats released 100% of their PPA in 9 to 12 hours. A good correlation was found between the in vivo and in vitro release data. Tissue pathology results showed no significant inflammatory tissue reactions. In conclusion, the partially ionized aqueous OC dispersions have the potential to be used as an implantable biodegradable carrier for amine drugs.