Release phenomena of insulin from an implantable device composed of a polyion complex of chitosan and sodium hyaluronate.

An implant controlled-release system for protein drug delivery based on a polyion complex device composed of chitosan (CS) and sodium hyaluronate (HA) was investigated. The conditions which generated the greatest amount of the polyion solid complex were studied to ascertain the formation of polyion complex between CS and HA. The greatest amount of the polyion complex was formed at the weight ratio of 3 to 7 (CS:HA) at pH 3.5. Furthermore, the CS-HA pellets were prepared and then drug release from CS-HA pellets was evaluated using insulin as a model drug. The results demonstrated that the insulin release from CS-HA pellets was markedly influenced by both the change in the polymer mixing ratio and the total pellet weight, whereas the compression pressure did not affect the release significantly. An artificial neural network (ANN) and biharmonic spline interpolation (HSI) were employed to predict the actual relation between causal factors and the release rate constant of insulin. Although both the ANN and HSI successfully represented a non-linear relationship between the formulation factors and the release rate constant, HSI methodology gave a better estimation than that of the ANN.

Effect of penetration enhancers on transdermal delivery of propofol.

To develop a transdermal dosage form of propofol (PF), in vitro skin permeability and in vivo absorbability of PF were investigated in rats, and the effectiveness of enhancers on the transdermal delivery of PF was estimated. Propylene glycol (PG), isopropyl myristate and macrogol were used as co-solvent type enhancers. L(-)-Menthol (MEN), D(+)-limonene, oleic acid, stearic acid, sucrose fatty acid esters and sodium dodecyl sulfate (SDS) were used as membrane-acting type enhancers. Among the co-solvent type enhancers, PG showed the highest enhancing effect in vitro. Furthermore, the synergistic effect of the combined use of PG and membrane-acting type enhancers was confirmed. Higher values of permeation parameters were observed with the combined use of PG and MEN, sucrose fatty acid esters or SDS. For the in vivo experiment, the addition of a smaller amount of PG was preferable to the amount used in the in vitro experiment. The synergistic effect of enhancers was observed with the combined use of PG and MEN. Our findings suggest that the combination of PG and MEN was useful as enhancers for the transdermal absorption of PF. These results provide useful information to develop a transdermal dosage form of PF as a sedative or a hypnotic.

Transdermal absorption of propofol in rats.

Propofol (PF), a highly lipophilic anesthetic, has several desirable properties, such as the rapid onset and cessation of its effects upon intravenous infusion. In this study, the transdermal absorption of PF was investigated with the aim of the development of an alternative route of administration. PF solutions containing isopropyl myristate (IPM), ethanol or propylene glycol (PG) at various concentrations were prepared and applied to the abdominal skin of rats. Petrolatum and fatty alcohol propylene glycol (FAPG) ointments containing PF were also prepared and applied to the dorsal skin. Eyelid opening was measured and the ratio of the measured value to the initial value was calculated to evaluate the level of the pharmacological effect of the preparation. The PG solution containing 80% PF achieved higher plasma PF concentrations than the 100% PF solution. The PF-FAPG ointment produced a higher plasma PF concentration than the PF-petrolatum ointment. Furthermore, a drowsy state was confirmed after transdermal administration of 42% PF-FAPG ointment. These results indicate that the combination of PF and PG was appropriate for the transdermal absorption of PF, and PF was absorbed through the rat skin to an extent sufficient to cause a continuous sedative effect.