Pharmaceutical compositions of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyriodin-2-yl)benzoic acid and administration thereof

A pharmaceutical composition comprising a plurality of granules, the composition comprising:

• a. Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A in an amount ranging from about 20 wt % to about 80 wt % by weight of the composition;
• b. a filler in an amount ranging from about 20 wt % to about 50 wt % by weight of the composition of a filler;
• c. a disintegrant in an amount ranging from a from about 1 wt % to about 5 wt % by weight of the composition;
• d. a surfactant in an amount ranging from about 2 wt % to about 0.3 wt % by weight of the composition;
• e. a diluent in an amount ranging from about 1 wt % to about 30 wt % by weight of the composition;
• f. a lubricant in an amount ranging from about 0.3 wt % to about 5 wt % by weight of the composition;
• and
• g. at least one of a binder in an amount from about 20 wt % to about 45 wt % by weight of the composition or a glidant in an amount ranging from about 0.05 wt % to about 2 wt % by weight of the composition.

A dosage unit form which comprises:

• a. about 30 wt % of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A by weight of the composition;
• b. about 42 wt % of microcrystalline cellulose by weight of the composition;
• c. about 21 wt % of mannitol by weight of the composition;
• d. about 3 wt % of sodium croscarmellose sodium by weight of the composition;
• e. about 1 wt % of sodium lauryl sulfate by weight of the composition;
• f. about 2.5 wt % of magnesium stearate by weight of the composition;
• and
• g. about 0.5 wt % of colloidal silica by weight of the composition;
• a. about 50 wt % of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A;
• b. about 30 wt % of microcrystalline cellulose by weight of the composition;
• c. about 13 wt % of mannitol by weight of the composition;
• d. about 2 wt % of sodium croscarmellose sodium by weight of the composition;
• e. about 4 wt % of polyvinylpyrrolidone by weight of the composition;
• f. about 1 wt % of sodium lauryl sulfate by weight of the composition;
• and
• g. about 0.5 wt % of magnesium stearate by weight of the composition;
• a. about 60 wt % of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A;
• b. about 20 wt % of microcrystalline cellulose by weight of the composition;
• c. about 13 wt % of mannitol by weight of the composition;
• d. about 2 wt % of sodium croscarmellose sodium by weight of the composition;
• e. about 4 wt % of polyvinylpyrrolidone by weight of the composition;
• f. about 1 wt % of sodium lauryl sulfate by weight of the composition;
• and
• g. about 0.5 wt % of magnesium stearate by weight of the composition;
• a. about 60 wt % of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or
• Compound 1 HCl Salt Form A;
• b. about 34 wt % of microcrystalline cellulose by weight of the composition;
• c. about 13 wt % of mannitol by weight of the composition;
• d. about 4 wt % of sodium croscarmellose sodium by weight of the composition;
• e. about 4 wt % of polyvinylpyrrolidone by weight of the composition;
• f. about 1 wt % of sodium lauryl sulfate by weight of the composition;
• and
• g. about 1.5 wt % of magnesium stearate by weight of the composition;
• a. about 150 to 250 mg of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A;
• b. about 40 to 50 mg of mannitol;
• c. about 120 to 130 mg of microcrystalline cellulose;
• d. about 10 to 20 mg of croscarmellose sodium;
• e. about 10 to 20 mg of polyvinylpyrrolidone;
• f. about 1 to 5 mg of sodium lauryl sulfate;
• and
• g. about 1 to 5 mg of magnesium stearate;
• a. about 200 mg of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A;
• b. about 43 mg of mannitol;
• c. about 123 mg of microcrystalline cellulose;
• d. about 15 mg of croscarmellose sodium;
• e. about 13 mg of polyvinylpyrrolidone;
• f. about 3 mg of sodium lauryl sulfate;
• and
• g. about 4 mg of magnesium stearate;
• or
• a. about 70 wt % of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or
• Compound 1 HCl Salt Form A;
• b. about 12 wt % of microcrystalline cellulose by weight of the composition;
• c. about 11 wt % of mannitol by weight of the composition;
• d. about 2 wt % of sodium croscarmellose sodium by weight of the composition;
• e. about 4 wt % of polyvinylpyrrolidone by weight of the composition;
• f. about 1 wt % of sodium lauryl sulfate by weight of the composition;
• and
• g. about 0.5 wt % of magnesium stearate by weight of the composition.

A method of producing a pharmaceutical composition comprising the steps of:

• combining a therapeutically effective amount of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A and at least one granulation excipient selected from the group consisting of:
• a binder;
• a glidant;
• a surfactant;
• a lubricant;
• a disintegrant;
• a filler, a diluent and combinations thereof to form an admixture;
• mixing the admixture;
• and compacting the admixture to form the pharmaceutical composition.

A method of administering a tablet comprising orally administering to a patient at least once per day a tablet comprising:

• a. about 25 to 200 mg of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A;
• b. a filler;
• c. a diluent;
• d. a disintegrant;
• e. a surfactant;
• f. at least one of a binder and a glidant;
• and
• g. a lubricant.

A method of treating or lessening the severity of a disease in a subject comprising administering to the subject a tablet, pharmaceutical composition, or dosage unit form of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A, wherein the disease is selected from cystic fibrosis, asthma, smoke induced COPD, chronic bronchitis, rhinosinusitis, constipation, pancreatitis, pancreatic insufficiency, male infertility caused by congenital bilateral absence of the vas deferens (CBAVD), mild pulmonary disease, idiopathic pancreatitis, allergic bronchopulmonary aspergillosis (ABPA), liver disease, hereditary emphysema, hereditary hemochromatosis, coagulation-fibrinolysis deficiencies, protein C deficiency, Type 1 hereditary angioedema, lipid processing deficiencies, familial hypercholesterolemia, Type 1 chylomicronemia, abetalipoproteinemia, lysosomal storage diseases, I-cell disease/pseudo-Hurler, mucopolysaccharidoses, Sandhof/Tay-Sachs, Crigler-Najjar type II, polyendocrinopathy/hyperinsulemia, Diabetes mellitus, Laron dwarfism, myleoperoxidase deficiency, primary hypoparathyroidism, melanoma, glycanosis CDG type 1, congenital hyperthyroidism, osteogenesis imperfecta, hereditary hypofibrinogenemia, ACT deficiency, Diabetes insipidus (DI), neurophyseal DI, neprogenic DI, Charcot-Marie Tooth syndrome, Perlizaeus-Merzbacher disease, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, progressive supranuclear plasy, Pick's disease, several polyglutamine neurological disorders, Huntington's, spinocerebullar ataxia type I, spinal and bulbar muscular atrophy, dentatorubal pallidoluysian, myotonic dystrophy, spongiform encephalopathies, hereditary Creutzfeldt-Jakob disease (due to prion protein processing defect), Fabry disease, Straussler-Scheinker syndrome, COPD, dry-eye disease, Sjogren's disease, Osteoporosis, Osteopenia, Gorham's Syndrome, chloride channelopathies, myotonia congenita (Thomson and Becker forms), Bartter's syndrome type III, Dent's disease, hyperekplexia, epilepsy, hyperekplexia, lysosomal storage disease, Angelman syndrome, Primary Ciliary Dyskinesia (PCD), inherited disorders of the structure and/or function of cilia, PCD with situs inversus (also known as Kartagener syndrome), PCD without situs inversus, or ciliary aplasia.