• Journal of Pharmaceutical Investigation
• /
• 제32권4호
• /
• pp.259-265
• /
• 2002

Piroxicam is one of the NSAID, which is used in the systemic and topical treatment of a variety of inflammatory conditions. Conventionally, for topical use, the drug is formulated in gel. We designed an phonophoretic drug delivery system to investigate the piroxicam permeability and the influence of ultrasound application (continuous mode, pulsed mode), frequency (1.0 MHz, 3.0 MHz) and intensity $(1.0\;w/cm^2,\;1.5\;w/cm^2,\;2.0\;w/cm^2)$ with 0.5% piroxicam gel. Per cutaneous absorption studies were performed in vitro models to determine the rate of drug absorption via the skin. Permeation study using hairless mouse skin was performed at $37^{\circ}C$ using buffered saline (pH 7.4, 10% propylene glycol solution) as the receptor solution. Anti-inflammatory activity was determined using carrageenan-induced foot edema model in rat. A pronounced effect of ultrasound on the skin absorption of the piroxicam was observed at all ultrasound energy level studied. Ultrasound was carried out for 10 hr. The highest permeation was observed at intensity of $2.0\;w/cm^2$, frequency of 1.0 MHz and continuous output. The inclusion of phonophoresis was found to improve significantly the skin permeation in vitro and the anti-inflammatory activity in vivo.

• Archives of Pharmacal Research
• /
• 제19권2호
• /
• pp.116-121
• /
• 1996

Antisense oligonucleotides seem to provide a promising new tool for the therapy. Choi et al. (1995) reported antisense phosphorothioate oligonucleotides (PS-ODN, 25 mer) complementary to TGF-.betha. mRNA designed for scar formation inhibitor to eliminate scars, which was caused by undesired collagen deposition due to overexpression of TGF-.betha., in wounded skin. PS-ODN were evaluated in vitro for skin penetration using normal and tape-stripped damaged rat skin. The in vitro skin transports were carried out with partially modified PS-ODN (6S) and fully modified PS-ODN (25S). The cumulative amount of PS-ODN (6S) penetrated through normal rat skin was $0.234{\pm}0.041{\mu}g/cm^2$ and that of tape-stripped damaged rat skin was $1.077{\pm}0.301{\mu}g/cm^2$ over 8 hrs. PS-ODN (25S) can not be found in receptor medium through normal skin due to high molecular weight (Mol.Wt.=8,000) and polyanionic charge. However, the cumulative amount of PS-ODN (25S) penetrated across damaged rat skin in PBS was $0.340{\pm}0.296{\mu}g/cm^2$ over 8 hrs. The absense of dermis raised the cumulative amount of PS-ODN (6S) penetrated through rat skin. And the fluxes of PS-ODN (6S) and PSODN (25S) at 8hrs across damaged rat skin were $134.63{\pm}37.67{\mu}g/cm^2$ h, and $42.50{\pm}36.95ng/cm^2$ h, respectively. While PS-ODN (25S) was stable in 10% heat inactivated fetal bovine serum (FBS) during 24 hrs, PS-ODN (6S) was less stable than PS-ODN (25S), but was markedly stable than unmodified phosphodiester. It is suggested that the cumulative amount of PS-ODN (6S) penetrated through damaged rat skin is larger than that of PS-ODN (25S) since the former is easier to degrade by nuclease than the latter and then is apt to penetrate into skin. Thus, PS-ODN represents a logical candidate for further evaluation due to the potential for delivery into the wounded skin.