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-10869835-B2
Publication Date
2020-12-22
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 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 document describes forming a reconstituted pharmaceutical formulation by reconstituting a lyophilized composition. The lyophilized composition comprises glibenclamide or a pharmaceutically acceptable salt thereof, at least one substantially pharmaceutically inert compound selected from specified sugars, polyols, and salts, and one or more alkali bases. Reconstitution is performed in deionized water at a glibenclamide concentration of about 0.2 mg/mL to about 1.0 mg/mL.
After reconstitution, the resulting pharmaceutical formulation has a pH greater than 8. The lyophilized composition is stable for at least 3 months at 25° C. and 60% relative humidity. The described formulation is suitable for intravenous use, and the document also addresses holding the formulation in a container for reconstitution.
The formulation design emphasizes the use of substantially pharmaceutically inert compounds such as sugars/polyols and salts, together with alkali bases to achieve the required pH. The document further describes embodiments in which the lyophilized composition is stable while being formulated without solubility-enhancing agents above a specified limit, and includes additional compositional constraints such as particular inert/base selections and reconstituted osmolality ranges.
Claims Coverage
The partial content identifies two independent claims, a method claim and a container claim, each built around the same inventive framework: reconstituting a glibenclamide-containing lyophilized composition in deionized water using specified substantially pharmaceutically inert compounds and one or more alkali bases to obtain a pH above 8, with stability for at least 3 months at 25° C. and 60% relative humidity.
Reconstituting a defined lyophilized glibenclamide composition in deionized water
Reconstituting a lyophilized composition that comprises glibenclamide or a pharmaceutically acceptable salt thereof and reconstituting in deionized water at a concentration of about 0.2 mg/mL to about 1.0 mg/mL.
Using substantially pharmaceutically inert compounds selected from sugars/polyols and salts
The lyophilized composition further comprises at least one substantially pharmaceutically inert compound selected from glucose, fructose, mannose, galactose, mannitol, sorbitol, lactose, trehalose, sucrose, sodium chloride and potassium chloride.
Employing alkali bases to achieve a pH greater than 8
The lyophilized composition comprises one or more alkali bases, and the formed reconstituted pharmaceutical formulation has a pH greater than 8.
Ensuring lyophilized composition stability at 25° C. and 60% relative humidity
The lyophilized composition is stable for at least 3 months at 25° C. and 60% relative humidity.
Providing the reconstituted formulation in a container
A container containing a reconstituted pharmaceutical formulation comprising a lyophilized composition reconstituted in deionized water at about 0.2 mg/mL to about 1.0 mg/mL glibenclamide or salt, where the reconstituted pharmaceutical formulation has a pH greater than 8 and the lyophilized composition is stable for at least 3 months at 25° C. and 60% relative humidity.
Across the independent claims, the inventive coverage centers on a defined lyophilized composition containing glibenclamide or its salt, substantially pharmaceutically inert compounds selected from specified sugars, polyols, and salts, and alkali bases. Reconstitution in deionized water produces a reconstituted formulation with pH greater than 8, and the lyophilized composition must be stable for at least 3 months at 25° C. and 60% relative humidity.
Stated Advantages
Lyophilized composition stability for at least 3 months at 25° C. and 60% relative humidity.
Formed reconstituted pharmaceutical formulation has a pH greater than 8.
Reconstituted pharmaceutical formulation suitable for intravenous administration.
Documented Applications
Intravenous administration of a reconstituted pharmaceutical formulation formed by reconstituting a lyophilized composition containing glibenclamide.
Use of a container holding the reconstituted pharmaceutical formulation formed by reconstituting the lyophilized composition in deionized water.
Interested in licensing this patent?