Compositions for Drug Administration
The present invention provides compositions and methods and for speeding the onset of drug action and reducing the first-pass effect drug metabolism in fast-dispersing drug formulations.
1 . A fast-dispersing drug formulation comprising a matrix material and an alkylsaccharide having a Tmax substantially less than, and a first-pass effect substantially less than that observed for an equivalent formulation not containing an alkylsaccharide.
2 . The formulation of claim 1 , further comprising olanzapine and 0.1% to 10% alkylsaccharide, and wherein the formulation exhibits a Tmax substantially less than six hours and a first-pass effect of less than 40%.
3 . The formulation of claim 1 , wherein the alkylsaccharide is dodecyl maltoside, tetradecyl maltoside, sucrose dodecanoate, or sucrose mono- and di-stearate.
4 . The formulation of claim 1 , wherein the first-pass effect is demonstrated by a reduction in the ratio of drug metabolite to un-metabolized drug.
5 . The formulation of claim 1 , wherein the alkylsaccharide concentration is selected to be less than or equal to 80% of an alkylsaccharide concentration determined to be maximal or near maximal buccal absorption thus providing an extended absorption curve as compared to the curve obtained with the concentration of alkylsaccharide determined to provide maximal or near maximal buccal absorption.
6 . The formulation of claim 1 , further comprising a substantially water-insoluble drug, wherein the drug is uniformly suspended in a lyophilizable gel.
7 . The formulation of claim 6 , wherein the drug is prepared in a fine particle form through micronization by milling, grinding, spray-dry dispersion, or combination thereof.
8 . The formulation of claim 1 , wherein the drug is melatonin, raloxifene, olanzapene or diphenhydramine
9 . A fast-dispersing drug formulation of melatonin comprising a matrix material and an alkylsaccharide having an absolute bioavailability when administered to buccal tissue greater than 50% and a substantially reduced first-pass effect as measured by a reduction in the ratio of circulating 6-sulfaoxymelatonin to unmodified melatonin.
10 . A fast-dispersing drug formulation of raloxifene comprising a matrix material and an alkylsaccharide suitable for forming a stable lyophilizable hydrogel that has an absolute bioavailability when administered to buccal tissue of at least 4% and a substantially reduced first-pass effect as measured by a reduction in the ratio of circulating raloxifene glucuronide conjugate concentration to unconjugated raloxifene.
11 . A fast-dispersing drug formulation of diphenhydramine comprising a matrix material and an alkylsaccharide suitable for forming a stable lyophilizable hydrogel that has a Tmax and time to onset of action of less than half as compared to that of an equivalent oral dose and a substantially reduced first-pass effect as measured by a reduction in the ratio of circulating inactive metabolites diphenhydramine glucuronide conjugate, dinordiphenhydramine, and diphenylmethoxyacetic acid concentrations to diphenhydramine.
12 . A method for providing an extended absorption curve by attenuating the alkylsaccharide concentration in a drug formulation to balance gastric and buccal delivery using the formulation of claim 1 .