Basic drug compositions with enhanced bioavailability

A composition comprising

• a basic drug, a drug which forms a zwitterion, or a salt of either, wherein said basic drug, zwitterionic drug, or salt of either is amorphous, admixed with
• a polymer selected from hydroxypropylmethylcellulose acetate succinate (HPMCAS), cellulose acetate trimellitate (CAT), hydroxypropylcellulose acetate phthalate (HPCAP), hydroxypropylmethyl cellulose acetate phthalate (HPMCAP), and methylcellulose acetate phthalate (MCAP);
• wherein said basic drug, zwitterionic drug, or salt of either has a dose to aqueous solubility ratio greater than 100 at pH 5.0 to 7.0;
• said composition effecting in vivo either a maximum drug concentration in serum or plasma of a test subject (Cmax) or an area under the curve (AUC) plotting the serum or plasma concentration of drug along the ordinate (Y-axis) against time along the abscissa (X-axis) that is at least 1.25 times the corresponding Cmax or AUC effected by a control composition comprising an equivalent quantity of drug and excipients, but without said polymer.

A method of administering a basic drug, a drug which forms a zwitterion, or a salt of either, wherein said basic drug, zwitterionic drug, or salt of either is amorphous, comprising co-administering, to a patient in need of said drug:

• a) said basic drug, zwitterionic drug, or salt of either, wherein said basic drug, zwitterionic drug, or salt of either has a dose to aqueous solubility ratio greater than 100 at pH 5.0 to 7.0;
• and
• b) a polymer selected from hydroxypropylmethylcellulose acetate succinate (HPMCAS), cellulose acetate trimellitate (CAT), hydroxypropylcellulose acetate phthalate (HPCAP), hydroxypropylmethyl-cellulose acetate phthalate (HPMCAP), and methylcellulose acetate phthalate (MCAP);
• wherein, in the absence of said polymer, said basic drug, zwitterionic drug or salt of either has a solubility in a first aqueous use environment having a pH of 1.0 to 2.0 which is at least 3-fold the solubility of said drug in a second aqueous use environment having a pH in the range of 5.0 to 7.0;
• and wherein said polymer is co-administered in an amount such that, at any time during the first two hours following the time at which said basic drug, zwitterionic drug, or salt of either has been introduced from said first use environment into said second use environment, the concentration of said basic drug, zwitterionic drug, or salt of either in said second use environment is increased to at least 1.5-fold the concentration of said basic drug, zwitterionic drug, or salt introduced from said first environment into said second environment in a control composition not containing said polymer.

A composition comprising

• a) a basic drug, a drug which forms a zwitterion, or a salt of either, wherein said basic drug, zwitterionic drug, or salt of either is crystalline, admixed with
• b) a polymer selected from hydroxypropylmethylcellulose acetate succinate (HPMCAS), cellulose acetate trimellitate (CAT), cellulose acetate phthalate (CAP), hydroxypropylcellulose acetate phthalate (HPCAP), hydroxypropylmethyl-cellulose acetate phthalate (HPMCAP), and methylcellulose acetate phthalate (MCAP);
• wherein, in the absence of said polymer, said basic drug, zwitterionic drug or salt has a solubility in a first aqueous use environment having a pH of 1.0 to 2.0 which is at least 3-fold the solubility of said drug in a second aqueous use environment having a pH in the range of 5.0 to 7.0;
• and wherein, in said composition, said polymer is present in an amount such that, at any time during the first two hours following the time at which said composition has been introduced from said first use environment into said second use environment, the concentration of said dissolved basic drug, zwitterionic drug, or salt of either in said second use environment is at least 1.5-fold the concentration of said dissolved basic drug, zwitterionic drug, or salt introduced from said first environment into said second environment in a control composition not containing said polymer.

A method of administering a basic drug, a drug which forms a zwitterion, or a salt of either, wherein said basic drug, zwitterionic drug, or salt of either is crystalline, comprising co-administering, to a patient in need of said drug:

• a) said basic drug, zwitterionic drug, or salt of either;
• and
• b) a polymer selected from hydroxypropylmethylcellulose acetate succinate (HPMCAS), cellulose acetate trimellitate (CAT), cellulose acetate phthalate (CAP), hydroxypropylcellulose acetate phthalate (HPCAP), hydroxypropylmethyl-cellulose acetate phthalate (HPMCAP), and methylcellulose acetate phthalate (MCAP);
• wherein, in the absence of said polymer, said basic drug, zwitterionic drug or salt of either has a solubility in a first aqueous use environment having a pH of 1.0 to 2.0 which is at least 3-fold the solubility of said drug in a second aqueous use environment having a pH in the range of 5.0 to 7.0;
• and wherein said polymer is co-administered in an amount such that, at any time during the first two hours following the time at which said basic drug, zwitterionic drug, or salt of either has been introduced from said first use environment into said second use environment, the concentration of said basic drug, zwitterionic drug, or salt of either in said second use environment is increased to at least 1.5-fold the concentration of said basic drug, zwitterionic drug, or salt introduced from said first environment into said second environment in a control composition not containing said polymer.