Pharmaceutical compositions for substituted quinazolinones

Inventors

Shenoy, Narmada R.

Assignees

Resverlogix Corp

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 substituted quinazolinone solid immediate-release formulations comprising an active ingredient of 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one and pharmaceutically acceptable salts, stereoisomers, hydrates, and tautomers thereof. The formulations are formulated for oral administration and immediate release, with the active ingredient present in defined weight-percentage ranges.

The problem being solved is the formulation of an immediate-release oral solid dosage form for regulating ApoA-I expression and treating or preventing cardiovascular-, cholesterol-, or lipid-related disease or disorder, where solubility and dissolution can be challenging. The disclosure addresses formulation design by specifying a solid immediate-release formulation composition with defined excipients, including microcrystalline cellulose, colloidal silicon dioxide as a glidant, and sodium starch glycolate and/or croscarmellose sodium as disintegrants.

In the provided embodiments and exemplars, specific formulations are described using fixed excipient levels alongside alternative active-ingredient content regimes. The disclosure further includes example oral dosage forms such as capsules and includes dissolution testing results used to support immediate-release behavior. The disclosed active ingredient salt form includes hydrochloride, and the formulation compositions are described in relation to regulating ApoA-I expression and addressing diseases including atherosclerosis, metabolic syndrome, diabetes mellitus, and certain cancers.

Beyond cardiovascular and lipid disorders, the substituted quinazolinone immediate-release formulation is described for treating IL-6 mediated inflammatory disease and for treating viral infections selected from human immunodeficiency virus (HIV), herpes virus, and papilloma virus, as well as certain cancers selected to include midline carcinoma. The disclosed cancer targets include midline carcinoma and c-Myc-driven malignancies, and the formulation context links the BET inhibitor activity and ApoA-I regulation to these therapeutic areas.

Claims Coverage

The patent includes three independent claims. Across these claims, the coverage centers on a specific substituted quinazolinone active ingredient and an oral immediate-release pharmaceutical formulation with defined microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycolate, and magnesium stearate, using multiple alternative active-ingredient weight-percentage regimes.

Across the independent claims, the inventive coverage is directed to oral immediate-release formulations containing a specific substituted quinazolinone active ingredient and pharmaceutically acceptable forms with defined excipients and alternative active-ingredient weight-percentage regimes. The same formulation framework is applied to treating cardiovascular-/cholesterol-/lipid-related disorders, specified cancers, IL-6 mediated inflammatory disease, and infections including HIV, herpes virus, and papilloma virus, and bacterial infection.

Stated Advantages

Documented Applications