Formulation for oral delivery of proteins, peptides and small molecules with poor permeability

A delayed release oral pharmaceutical dosage form comprising:

• a pharmaceutical formulation comprising:
• a synthetic or natural poorly permeable CGRP inhibitor or salt or solvate thereof in an amount 0.01-20 wt. % of the total weight of the formulation;
• a lipophilic phase comprising triglycerides of fatty acids in an amount of 50-80 wt. % of the total weight of the formulation;
• and
• at least one lipophilic surfactant comprising partial esters of polyol and fatty acids in an amount of 10-50 wt. % of the total weight of the formulation, wherein the delayed release dosage form is a coated dosage form whose release is pH dependent,
• wherein the synthetic or natural poorly permeable CGRP inhibitor is a small molecule CGRP receptor antagonist and the small molecule CGRP receptor antagonist is (R)—N-(3-(7-methyl-1H-indazol-5-yl)-1-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide (BHV-3500), wherein the dosage form is a capsule.

A method for treating a patient, comprising administering to a person in need thereof an effective amount of an oral pharmaceutical formulation in a capsule, the oral pharmaceutical formulation comprising:

• a synthetic or natural poorly permeable CGRP inhibitor or salt or solvate thereof in an amount 0.01-20 wt. % of the total weight of the formulation;
• a lipophilic phase comprising triglycerides of fatty acids in an amount of 50-80 wt. % of the total weight of the formulation;
• and
• at least one lipophilic surfactant comprising partial esters of polyol and fatty acids in an amount of 10-50 wt. % of the total weight of the formulation,
• wherein the synthetic or natural poorly permeable CGRP inhibitor is a small molecule CGRP receptor antagonist and the small molecule CGRP receptor antagonist is (R)—N-(3-(7-methyl-1H-indazol-5-yl)-1-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide (BHV-3500).