Design of a polyvinyl alcohol hydrogen containing phospholipid as controlled-release vehicle for rectal administration of (+/-)-propranolol HCl

Polyvinyl alcohol hydrogels which contained phospholipid, egg yolk lecithin or hydrogenated soya lecithin were designed as a transrectal delivery system for propranolol hydrochloride. The hydrogel preparations containing phospholipid were prepared by a low-temperature crystallization method. The release profile of propranolol from hydrogel preparations containing phospholipid complied with Fickian diffusion (Higuchi model). The release of propranolol from the hydrogel preparation decreased with higher contents of phospholipid (approximately 2% w/w). In rats plasma concentrations of propranolol after rectal administration of hydrogel preparations containing phospholipid (1 and 2% w/w) were prolonged compared with those of rats receiving preparations without phospholipid.     

Long-term use of mizoribine in rheumatoid arthritis patients on hemodialysis

Small doses of mizoribine (MZR) were administered to five rheumatoid arthritis (RA) patients on hemodialysis (HD). A maintenance dose of 25 mg or less was administered either once per day or once following HD. The Lansbury activity index improved in all patients. The blood concentrations of MZR before and after HD were 0.33–1.79 μg/ml and 0–0.93 μg/ml, respectively. Hence, the rate of elimination by HD ranged from 50.3% to 83.4%. As far as side effects were concerned, alopecia was seen in two patients, and one patient developed shingles. However, the severity of these symptoms was mild and, after discontinuing or reducing the dose of MZR for a certain period of time, we were able to continue its administration. These findings suggest that the long-term administration of MZR is a useful treatment for RA patients on HD. Received: July 12, 2000 / Accepted: December 7, 2000     

Safety and efficacy of water-in-oil-in-water emulsion vaccines containing Newcastle disease virus haemagglutinin-neuraminidase glycoprotein

Subunit vaccines containing haemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus (NDV), formulated as water-in-oil-in-water (W/O/W) emulsions, were prepared. First, the suitable constituents of a W/O/W emulsion adjuvant were investigated with polyvalent vaccines using NDV, infectious bronchitis virus and Haemophilus paragallinarum. The W/O/W emulsion adjuvant, composed of the antigen in phosphate-buffered saline (PBS), liquid paraffin, squalene, diglyceryl monooleate, polysorbate 80 and PBS in a 30:25:10:5:2:28 ratio, induced a good antibody response with less adverse local reactions. HN protein of NDV was expressed by an improved baculovirus expression vector, a hybrid nucleopolyhedrovirus (HyNPV) between Autographa californica NPV and Bombyx mori NPV,and was prepared from silkworm pupae infected with the recombinant baculovirus, HyNPV-HN. Then, the W/O/W emulsion vaccine containing HN protein was prepared using the aforementioned constituents. Chickens showed 100, 100 and 80% protection against challenge exposure to virulent NDV at 4 weeks after vaccination with W/O/W emulsion vaccines containing 30, 6 and 3% of HyHPV-HN-infected pupae, respectively. The vaccines containing HN protein did not induce adverse local reactions at the site of injection. The subunit vaccine for NDV containing HN protein expressed in the recombinant baculovirus-infected pupae, formulated as a W/O/W emulsion vaccine composed of the antigen in PBS, liquid paraffin, squalene, diglyceryl monooleate, polysorbate 80 and PBS in a 30:25:10:5:2:28 ratio, was therefore found to be safe and effective.     

Evaluation of Polyvinyl Alcohol Hydrogel as a Sustained-Release Vehicle for Rectal Administration of Indomethacin

In order to evaluate an indomethacin poly vinyl 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.