Pharmaceutical compositions for substituted quinazolinones
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-9610251-B2
Publication Date
2017-04-04
Expiration Date
Abstract
The present disclosure relates to novel solid pharmaceutical formulations and process for their preparation. The present disclosure also provides, in part, methods of using the pharmaceutical formulations for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for the treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.
Core Innovation
The invention relates to solid immediate-release pharmaceutical formulations that include substituted quinazolinone compounds of Formula I as the active ingredient. The active ingredient is exemplified by 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one, including pharmaceutically acceptable salts, stereoisomers, hydrates, and tautomers. The formulations are formulated for oral administration and immediate release.
The formulations address poor aqueous solubility by defining quantitative roles and percentages for formulation components. Microcrystalline cellulose serves as a major filler, colloidal silicon dioxide serves as a glidant, sodium starch glycolate serves as a disintegrant, and magnesium stearate serves as a lubricant. Optional inclusion of sodium lauryl sulfate as a surfactant is described, and multiple formulation compositions are provided.
The documented rationale links the formulation design to improved dissolution and disintegration, aiming to improve bioavailability after oral dosing. The disclosed therapeutic context associates the substituted quinazolinone active ingredient with ApoA-I upregulation and BET inhibition, including inhibition of bromodomain and extra-terminal domain proteins, which is connected to treatment indications spanning cardiovascular/lipid disorders and multiple cancer types.
Claims Coverage
The independent claim defines an oral immediate-release pharmaceutical formulation with specified percentage-by-weight ranges for the active ingredient and defined amounts of microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycolate, and magnesium stearate, with multiple alternative active-ingredient concentration ranges. Dependent claims refine the independent claim by selecting a specific active-ingredient form, imposing particle-size ranges, and adding additional quantitative constraints such as disintegration time and active-ingredient mass ranges.
Oral immediate-release formulation of substituted quinazolinone active ingredient with defined excipient percentages
A pharmaceutical formulation for oral administration and immediate release comprising an active ingredient selected from 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one and pharmaceutically acceptable salts, stereoisomers, hydrates, and tautomers thereof, wherein the active ingredient is present in an amount from about 10% to about 12% by weight and the formulation further comprises about 82% to about 83% by weight of microcrystalline cellulose, about 2.5% by weight of colloidal silicon dioxide, about 4.0% by weight of sodium starch glycolate, and about 0.5% by weight of magnesium stearate; alternatively, the active ingredient is present in an amount from about 20% to about 22% by weight or about 31% to about 33% by weight or about 41% to about 43% by weight with corresponding microcrystalline cellulose ranges, and with the same colloidal silicon dioxide, sodium starch glycolate, and magnesium stearate amounts.
Hydrochloride salt active ingredient form
The formulation is characterized by using the hydrochloride salt of a specified substituted quinazolinone active ingredient.
Active ingredient particle size constraints
The formulation is characterized in that the active ingredient has a particle size in one of the specified micron ranges of about 1–250 microns, about 1–100 microns, or about 1–10 microns.
Disintegration time threshold for immediate release
The formulation has a disintegration time of 120 seconds or less.
Active ingredient mass range
The formulation comprises about 25–100 mg of an active ingredient.
Selected discrete active ingredient amounts
The formulation comprises an active ingredient amount selected from about 25 mg, about 50 mg, about 75 mg, and about 100 mg.
Overall claim coverage centers on an oral immediate-release solid formulation that specifies defined percentage-by-weight excipient composition around substituted quinazolinone active ingredient(s) of Formula I. Dependent claim refinements further restrict the active ingredient form, impose particle-size ranges, and add quantitative constraints on disintegration time and active-ingredient mass.
Stated Advantages
Improved dissolution and disintegration for oral dosing.
Improved bioavailability after oral dosing.
Documented Applications
Therapeutic use in cardiovascular disease and atherosclerosis and cholesterol/lipid disorders, including metabolic syndrome.
Therapeutic use in cancer, including NUT midline carcinoma and BET/c-Myc-related cancers, including c-Myc, n-Myc, and p-TEFb-related contexts.
Therapeutic context also includes inflammatory disease, Alzheimer’s disease, and diabetes.
Interested in licensing this patent?