CPC A61K 9/2081 (2013.01) [A61K 9/009 (2013.01); A61K 9/1652 (2013.01); A61K 9/5036 (2013.01); A61K 9/5047 (2013.01); A61K 31/5513 (2013.01)] | 25 Claims |
1. An alcohol-resistant controlled release oral pharmaceutical composition of lorazepam, comprising
(A) alcohol-resistant coated sustained release beadlets comprising (i) beadlets comprising lorazepam and a controlled release polymer in a sustained release formulation surrounded by an alcohol-resistant coating; and
(B) alcohol-resistant coated delayed sustained release beadlets comprising (i) beadlets comprising lorazepam and a controlled release polymer in a sustained release formulation, (ii) an enteric coating surrounding the beadlets, and (iii) an alcohol-resistant coating surrounding the beadlets, and wherein the alcohol-resistant coating may be interior to or exterior to the enteric coating;
wherein the alcohol-resistant coating comprises one or more ethanol-insoluble components selected from the group consisting of carbomers, polyethylene oxide polymers, xanthan gum, and alginate;
wherein the amount of lorazepam released from the alcohol-resistant coated sustained release beadlets and alcohol-resistant coated delayed sustained release beadlets is 75% or less than the amount of lorazepam released from the corresponding beadlets without the alcohol-resistant coating, when measured by dissolution testing at 37.0±0.5° C. and 100 rpm for two hours in an acidic ethanolic aqueous solution comprising 40% ethanol and 0.1 N HC1 solution in accordance with USP <711>, and
wherein the amount of lorazepam released from the alcohol-resistant coated sustained release beadlets and alcohol-resistant coated delayed sustained release beadlets is ±25% or less as compared to the amount of lorazepam released from a corresponding beadlets without the alcohol-resistant coating, when measured by dissolution testing at 37.0±0.5° C. and 100 rpm for two hours in an aqueous 0.1 N HC1 solution, in accordance with USP <711>.
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