In order to evaluate an indomethacin polyvinyl alcohol (PVA) hydrogel for rectal administration, the in vitro release characteristics of indomethacin from the hydrogel and indomethacin plasma concentrations after rectal administration were examined. The PVA hydrogel containing indomethacin was prepared by a low-temperature crystallization method. The release of indomethacin from the PVA hydrogel agreed with the Fickian diffusion model for 10 hr. Rectal administration of indomethacin hydrogels to rats yielded high indomethacin plasma concentrations, without producing a sharp peak, and a sustained-release effect. In dogs, the indomethacin hydrogel produced a similar sustained-release effect; however, the indomethacin plasma concentration was relatively low compared with that of an indomethacin suppository.

Subunit vaccines containing haemagglutinin-neuraminidase (HN) glycoprotein of

Preparations of beta-blockers, propranolol-HCl and atenolol, in poly(vinyl alcohol) (PVA) hydrogel were designed for the therapeutic treatment of hypertension by transrectal delivery. In vitro release characteristics and plasma drug concentration profiles after rectal administration in rats and dogs were examined. The PVA hydrogels containing beta-blockers were prepared by a low-temperature crystallization method. The release of beta-blockers from hydrogel preparations was consistent with Fickian diffusion (Higuchi model); the drug release versus the square root of release time profile gave a straight line over 60% of the total release process. The release of beta-blockers from hydrogel preparations increased at higher concentrations of PVA in the hydrogel preparations and was not affected by the pH of hydrogel preparations. Plasma concentrations of beta-blockers after rectal administration of hydrogels were higher than those after administration of suppositories (Witepsol H-15) in rats and dogs. The drug plasma concentrations increased at higher concentrations of PVA in hydrogel preparations. In the case of propranolol, which is a hepatic high-clearance drug, area under the blood concentration curve, 0-8 h after rectal administration of a hydrogel preparation (20% w/w PVA, pH 7.0) was 2.16 times and 5.26 times higher than those obtained with Witepsol H-15 suppository and oral administration, respectively. Rectal administration with PVA hydrogels is a favorable route for a hepatic high-clearance drug such as propranolol.

ABSTRACT. The relationship between release properties of the model antigen, bovine serum albumin (BSA), from formulations in vitro and immune response after administration of various oil adjuvanted vaccines containing liquid paraffin was examined in chickens. The vaccine prepared at an hydrophile-lipophile-balance (HLB) number of 4.8 showed slower release of BSA and higher immune response on injected chickens than that with an HLB number of 6.0. Decreases of aqueous volume ratio in the formulation also led to slower release of BSA and higher immune response. The slower release rate of BSA showed higher ELISA antibody titer even at 20 weeks after vaccination. The ELISA antibody titer inversely was related to the constant release rate, k, calculated from the in vitro release test. The correlation coefficient was 0.863. The immune response of oil adjuvanted vaccines containing Haemophilus paragallinarum agreed well with these results with BSA. Our results indicated that a stronger and more prolonged immune response of oil adjuvanted vaccines was achieved by slower release rate of antigen from the formulation. In addition, there was a good correlation between immune response and the value of k.-KEY WORDS: bovine serum albumin, controlled release, immune response, infectious coryza, oil adjuvanted vaccine.