Formulations and methods for lyophilization and lyophilates provided thereby
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8277845-B2
Publication Date
2012-10-02
Expiration Date
Abstract
The present invention provides compositions, methods for lyophilizing compounds and making pharmaceutical compositions, and kits providing solutions and lyophilized formulations of compounds. The compositions, methods, and kits are particularly useful in pharmaceutical applications involving therapeutic agents that have low solubility at low pH and medium pH values. Certain embodiments provide methods for lyophilizing compounds in liquid solutions, which include the steps of: a) preparing aqueous solutions of a compound of interest in the absence of buffer; b) adjusting the pH to high values of pH in order to increase the solubility of the compound of interest; and c) freeze-drying the solution to provide a lyophilized solid composition. Aqueous solutions including buffer are also disclosed. Lyophilized formulations, including micronized and non-micronized powders, are provided.
Core Innovation
The invention relates to lyophilization and pharmaceutical formulations for poorly soluble weak acids, including sulphonylureas such as glibenclamide. It uses aqueous, buffer-free solutions in which solubility of glibenclamide is increased by adjusting the solution to high pH prior to freeze-drying.
The lyophilized glibenclamide solid pharmaceutical composition includes a lyophilized glibenclamide powder that is substantially free of buffer and is substantially free of other agents that enhance the solubility of glibenclamide. The formulation further includes one or more substantially pharmaceutically inert compounds together with one or more alkali bases.
In examples described in the document, the lyophilized glibenclamide powders and compositions include micronized and non-micronized forms and can include combinations with other pharmaceutically active agents. Stability and reconstitution performance are described for lyophilized glibenclamide under storage conditions, along with formulation details involving pharmaceutically inert bulking agents and alkali bases.
Claims Coverage
The independent claim contains three core inventive areas: (i) a lyophilized glibenclamide powder that is substantially free of buffer and substantially free of solubility-enhancing agents, (ii) inclusion of pharmaceutically inert compounds together with alkali bases, and (iii) quantitative constraints on buffer content and inert-compound loading relative to glibenclamide.
Buffer-free lyophilized glibenclamide powder substantially free of solubility-enhancing agents
A solid pharmaceutical composition comprising a lyophilized glibenclamide powder substantially free of buffer and being substantially free of other agents that enhance the solubility of glibenclamide, wherein said lyophilized glibenclamide powder comprises less than about 1% w/w buffer.
Inert compounds with alkali bases in a specific inert-to-glibenclamide ratio
A solid pharmaceutical composition comprising one or more substantially pharmaceutically inert compounds and one or more alkali bases, wherein the weight of substantially pharmaceutically inert compounds comprises at least about 10 times the weight of glibenclamide in the solid pharmaceutical composition.
Inert compound selection limited to sugars and salts
The solid pharmaceutical composition includes pharmaceutically inert compounds selected from glucose, fructose, mannose, galactose, mannitol, sorbitol, lactose, trehalose, sucrose, sodium chloride, and potassium chloride.
Alkali base limited to sodium hydroxide or potassium hydroxide
The alkali base is sodium hydroxide or potassium hydroxide.
Tightened buffer constraint below 0.1% w/w
The solid pharmaceutical composition includes a buffer amount of less than about 0.1% w/w.
Higher inert-to-glibenclamide weight ratio
The solid pharmaceutical composition includes pharmaceutically inert compounds whose weight is at least about 30 times the weight of glibenclamide.
Pharmaceutically inert bulking agent selected from monosaccharides or disaccharides
The pharmaceutically inert bulking agent is selected from monosaccharides or disaccharides.
Overall, the claim coverage centers on a buffer-free lyophilized glibenclamide powder, combined with alkali bases and pharmaceutically inert compounds in a defined inert-to-glibenclamide weight ratio. Dependent claims specify example inert sugars/salts, constrain the alkali base to sodium hydroxide or potassium hydroxide, and further limit the inert component to mono-/disaccharide bulking agents.
Stated Advantages
Improved reconstitution of lyophilized glibenclamide.
Acceptable stability of lyophilized glibenclamide under storage conditions.
Documented Applications
Solid pharmaceutical compositions for poorly soluble weak acids, including sulphonylureas such as glibenclamide, provided as lyophilized glibenclamide powders and compositions.
Compositions including lyophilized glibenclamide combined with other pharmaceutically active agents, including combinations referenced in the document.
Use of lyophilized glibenclamide formulations described with micronized and non-micronized glibenclamide powder forms.
Interested in licensing this patent?