PubMed Health⌕ Search

Biomedical subjects

R D Gokhale

Publications and source records attributed to R D Gokhale.

6 recordsLinked to original sources
PubMed1993

In-vitro permeation of some beta-blockers across the hairless mouse skin.

To support the development of a suitable transdermal dosage form for beta-blockers, in-vitro, skin permeation studies of nine beta-blockers were conducted at 37 degrees C across the excised abdominal skin of hairless mouse mounted on the receptor compartment of a two-chambered Valia-Chien glass diffusion cell. The drugs varied in lipophilicity, whereas pKa values were comparable. Permeability coefficients were calculated from the steady-state flux values. Agreement was found between the permeability coefficient and the drug lipophilicity, expressed as the octanol-buffer distribution coefficient.

Adrenergic beta-Antagonists↗
PubMed1992

In-vitro assessment of a matrix system of levobunolol.

In order to study the feasibility of systemic delivery of levobunolol transdermally, a matrix-type delivery system was fabricated using a silicone elastomer. The relationship between loading dose and skin permeation rate was evaluated in-vitro using hairless mouse skin mounted on the stirred receptor compartment of the Keshary-Chien glass diffusion cell maintained at 37 degrees C. The concentration of levobunolol in the receptor compartment was determined by HPLC. A similar study without using the skin was carried out to determine the effect of loading dose on the release of levobunolol from discs. It was observed that the release of drug from disc followed a matrix-diffusion controlled (Q) vs square root of time relationship at different loading doses. In contrast, the results of skin permeation of levobunolol from transdermal discs containing different loading doses showed a linear Q vs time relationship indicating a constant zero order skin permeation rate at each loading dose. Skin permeation of levobunolol appeared to reach a plateau at a 5% (w/w) loading dose in the disc indicating the attainment of equilibrium concentration of levobunolol in the skin.

Administration, Cutaneous↗
PubMed1987

Physicochemical determinants of drug diffusion across the conjunctiva, sclera, and cornea.

This investigation examined some of the barrier properties of the conjunctival, scleral, and corneal membranes. The diffusion of nadolol, timolol, propranolol, penbutolol, sucrose, and inulin was measured across the isolated corneal and scleral membranes of the rabbit using a two-chamber glass diffusion cell. Drug absorption across the cornea and the conjunctiva was studied in vivo by measuring precorneal drug clearance. The drug samples were analyzed either by HPLC or liquid scintillation counting (LSC). For all the compounds tested, the scleral permeability was significantly higher than the respective corneal permeability. The permeability coefficients of the beta-blockers varied in the following manner: propranolol > penbutolol > timolol > nadolol for the cornea, and penbutolol > propranolol > timolol > nadolol for the sclera. The cornea offered substantially more resistance to inulin, a polar, macromolecular substance, than did the conjunctiva. However, the cornea and conjunctiva offered comparable resistance to the smaller and less polar drug timolol. This information may serve as a basis for optimizing the intraocular delivery of drugs that are poorly absorbed across the cornea due to their physicochemical properties.

Animals↗
PubMed1985

Prazosin alters free and total plasma digoxin levels in dogs.

Digoxin has been associated with a variety of drug interactions. Studies in our laboratory indicate that single doses of prazosin may alter plasma steady-state digoxin levels. Adult mongrel dogs were given digoxin tablets orally (0.008 mg/kg, twice daily) until steady-state levels of digoxin were reached. Dogs were then tested in a cross-over study with prazosin and saline. Plasma samples were assayed for both free and total plasma digoxin via radioimmunoassay. Free drug was separated from protein bound drug utilizing a micropartition system. Plasma binding of digoxin as well as nonspecific tissue binding was reduced by prazosin and resulted in an increased fraction of free digoxin in plasma. The increase in free digoxin leads to an increase in the pool of digoxin available for pharmacologic activity. Acute experiments demonstrated such an increased pharmacologic effect of digoxin in the presence of prazosin. Prazosin pretreatment prior to a continuous digoxin infusion significantly increased the positive inotropic effect of digoxin compared to dogs receiving only digoxin.

Animals↗