Evaluation of CZ-resin vials for packaging protein-based parenteral formulations.

Due to the fact that some proteins have a tendency to bind to glass surfaces, plastic CZ-resin vials were evaluated as an alternative material to glass vials for packaging protein-based parenteral formulations. Physico-chemical tests including protein binding, extractable evaluation, oxygen permeation, light transmission and moisture loss were performed. Data show that two proteins (A and B) were found to bind to USP type I glass but not to CZ-resin. The CZ-resin vials passed all USP test specifications for extractables (organic extractable, non-volatile residue and residue on ignition). The oxygen permeation rate (79.06 cm(3)mm/m(2)24 h atm) was consistent with that reported by the vendor (67 cm(3)mm/m(2)24 h atm). The value obtained for light transmission, which was also found to be consistent with that reported by the vendor, shows that these vials offer no protection from light. The average moisture loss from 2 cm(3) vials filled with water was gravimetrically determined to be 0.04 mg/day/vial when the vials were stored at 40 degrees C/75% relative humidity (RH). Assuming a 1cm(3) product fill, this corresponds to approximately a 3% loss over a 2-year period. However, moisture loss was found to be negligible at the typical storage condition of 5 degrees C for protein formulations. The physico-chemical tests indicate that CZ-resin vial is a suitable candidate for packaging parenteral formulations since it shows low moisture loss at typical storage condition of 5 degrees C, and does not leach out extractables. However, it should not be used for light-sensitive and oxygen-sensitive parenteral formulations. For proteins A and B, the CZ-resin vial is a viable alternate to the use of glass vials since it offered significantly less protein binding. Protein binding in general, should be evaluated on a case by case basis, since it may vary for different proteins and under different formulation conditions.

Nasal delivery of [14C]dextromethorphan hydrochloride in rats: levels in plasma and brain.

Dextromethorphan (DM) is a neuroprotective agent. The mechanism of action is believed to be by N-methyl-D-aspartate receptor blockade. The concentration of DM in the brain is believed to be dose and route dependent. Delivery by the nasal route has received a lot of attention recently, because drug absorption from this route follows intravenous profiles with no first-pass effect. The uptake of DM in the brain from the nasal route was 65.9% compared with the intravenous route, whereas the plasma bioavailability from the nasal route was 78.8%. The nasal route is a viable alternative to the parenteral route for DM administration.

Effect of iontophoresis on in vitro skin permeation of an analogue of growth hormone releasing factor in the hairless guinea pig model.

The shortened analogue of growth hormone releasing factor (GRF) Ro 23-7861 (1) has a molecular weight of 3929 daltons [equivalent to GRF (1-29)] and is more potent than the endogenous GRF (1-44). The in vitro hairless guinea pig model and vertical and horizontal diffusion cell assemblies were used to study the effect of iontophoresis on the permeability to skin of 1. The transport of 1 across the skin was studied by monitoring the rate of its appearance in the receiver compartment with a radioimmunoassay. No permeability of 1 was observed without iontophoresis, whereas with iontophoresis, the permeability of 1 was significant. For example, at a current density of 0.23 mA/cm2 and buffer concentration of 0.05 M, the flux of 1 was 56.8 +/- 8.21 ng/cm2.h. The flux of 1 was independent of the design of the permeation apparatus, the electrodes, the donor and receiver volumes, the type of current (constant or pulsed), and the frequency of the pulsed current. The flux of 1 increased curvilinearly with the increase in salt concentration of the buffer and linearly with the increase in current.