Flutamide compositions and preparations

A method of providing a therapeutic effect against prostatic adenocarcinoma and benign prostate hypertrophy comprising administering to a male mammal in need of treatment a therapeutically effective amount of a pharmaceutical composition in a unit dosage form comprising a therapeutically effective amount of flutamide API having a specific surface area of at least 0.35 m2/cm3, or a therapeutically acceptable salt thereof, together with at least one pharmaceutically acceptable excipient, diluent, or carrier, in association with a therapeutically effective amount of the formula:

• PGlu—His—Trp—Ser—Tyr—X—Y—Arg—Pro—Z Formula I
• wherein
• a) Z is GLy—NH2, Y is Leu and X is Gly;
• b) Z is Gly—NH2, Y is Leu, X is DN Leu, DN Val, D abu (α-aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu lle, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (Otbu), D Gly (Otbu), D Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, D Met, ε-lauryl-D-Lys, ε-dextran-D Lys;
• c) Z is NH-cyclopropyl or —NH—Alk wherein Alk is alkyl of 1 to 3 carbon atoms, Y is Leu and X is D Ser (tbu), D Thr (tbu), D Asp (Otbu), D Glu (Otbu), D Orn (boc), D Lys (boc);
• d) Z is —NH—CH3, —NH—CH2—CH3, —NH—CH2—CH2CH3, —NH—CH2—CH2—OH,
• Y is Leu and X is Gly;
• e) Z is NH—CH2—CH3, Y is Leu and X is D Trp, D Leu, D Ala, D Ser (tbu), D Tyr, D Lys, Ala;
• f) Z is Gly—NH2, or —NH—CH2—CH3, Y is Naα Me Leu and X is Gly;
• g) Z is —NH-cyclopropyl, Y is Leu and X is D Leu;
• or
• h) Z is Gly—NH2, —NH-cyclopropyl or —NHAlk′ wherein Alk′ is alkyl of 1 to 3 carbon atoms, Y is Ser (but), Cys (but), Asp (Obut), Glu (Obut), Orn (boc), Lys (boc) and X is Gly, or a pharmaceutically acceptable salt thereof.

A method of providing a therapeutic effect against prostatic adenocarcinoma and benign prostate hypertrophy comprising administering to a male mammal in need of treatment a therapeutically effective amount of a pharmaceutical composition in a unit dosage form comprising a therapeutically effective amount of flutamide API having a specific surface area of at least 0.35 m2/cm3 and also having an X90 value which is less than 130.0μ, or a therapeutically acceptable salt thereof, together with at least one pharmaceutically acceptable excipient, diluent, or carrier, in association with a therapeutically effective amount of the formula:

• PGlu—His—Trp—Ser—Tyr—X—Y—Arg—Pro—Z Formula I
• wherein
• a) Z is GLy—NH2, Y is Leu and X is Gly;
• b) Z is Gly—NH2, Y is Leu, X is DN Leu, DN Val, D abu (α-aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu lle, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (Otbu), D Gly (Otbu), D Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, D Met, ε-lauryl-D-Lys, ε-dextran-D Lys;
• c) Z is NH-cyclopropyl or —NH—Alk wherein Alk is alkyl of 1 to 3 carbon atoms, Y is Leu and X is D Ser (tbu), D Thr (tbu), D Asp (Otbu), D Glu (Otbu), D Orn (boc), D Lys (boc);
• d) Z is —NH—CH3, —NH—CH2—CH3, —NH—CH2—CH2CH3, —NH—CH2—CH2—OH,
• Y is Leu and X is Gly;
• e) Z is NH—CH2—CH3, Y is Leu and X is D Trp, D Leu, D Ala, D Ser (tbu), D Tyr, D Lys, Ala;
• f) Z is Gly—NH2, or —NH—CH2—CH3, Y is Naα Me Leu and X is Gly;
• g) Z is —NH-cyclopropyl, Y is Leu and X is D Leu;
• or
• h) Z is Gly—NH2, —NH-cyclopropyl or —NHAlk′ wherein Alk′ is alkyl of 1 to 3 carbon atoms, Y is Ser (but), Cys (but), Asp (Obut), Glu (Obut), Orn (boc), Lys (boc) and X is Gly, or a pharmaceutically acceptable salt thereof.