High surface-area lyophilized compositions comprising arsenic for oral administration in patients

A method for preparing an oral pharmaceutical formulation comprising a lyophilized composition comprising arsenic or lyophilized arsenic trioxide (As2O3), said method comprising:

• (A) solubilizing As2O3 powder in an aqueous medium to form an As2O3 solution;
• (B) lyophilizing said As2O3 solution to generate a lyopremix;
• (C) sifting said lyopremix to generate lyophilized As2O3 powder;
• (D) optionally, adding at least one bulking agent to said lyophilized As2O3 powder;
• (E) optionally, adding one or more lubricants to said lyophilized As2O3 powder to generate said oral formulation of As2O3.

A method for increasing the surface area of original API powder comprising arsenic trioxide, from about 5× to about 80× comprising the steps of:

• (A) solubilizing As2O3 powder in an aqueous medium to form an As2O3 solution, comprising the steps of:
• (I) adding an alkalizing agent to the As2O3 powder in a vessel, with or without stirring and with or without addition of water, to render a pH of about 12 or higher;
• (II) adding an acid to said vessel, with or without stirring and with or without addition of water, to adjust the pH to from about 7 to about 8;
• (III) optionally, adding a surfactant to said vessel, with or without stirring and with or without addition of water, and
• (IV) optionally, adding water to said vessel to generate an As2O3 solution with or without stirring;
• and
• (B) lyophilizing said As2O3 solution comprising the steps of:
• (V) freezing said As2O3 solution to generate a frozen As2O3 product;
• and
• (VI) drying said As2O3 product to generate said lyophilized composition comprising arsenic.

A method for increasing the solubility of arsenic trioxide powder in water or in alcohol by about 2× to about 30×, said method comprising the steps of:

• (A) solubilizing As2O3 powder in an aqueous medium to form an As2O3 solution, comprising the steps of:
• (I) adding an alkalizing agent to the As2O3 powder in a vessel, with or without stirring and with or without addition of water, to render a pH of about 12 or higher;
• (II) adding an acid to said vessel, with or without stirring and with or without addition of water, to adjust the pH to from about 7 to about 8;
• (III) optionally, adding a surfactant to said vessel, with or without stirring and with or without addition of water, and
• (IV) optionally, adding water to said vessel to generate an As2O3 solution with or without stirring;
• and
• (B) lyophilizing said As2O3 solution comprising the steps of:
• (V) freezing said As2O3 solution to generate a frozen As2O3 product;
• and
• (VI) drying said As2O3 product to generate said lyophilized composition comprising arsenic.

A method for increasing the dissolution of a pharmaceutical composition comprising arsenic, by at least five times over the original API comprising arsenic trioxide, said method comprising the steps of:

• (A) solubilizing As2O3 powder in an aqueous medium to form an As2O3 solution, comprising the steps of:
• (I) adding an alkalizing agent to the As2O3 powder in a vessel, with or without stirring and with or without addition of water, to render a pH of about 12 or higher;
• (II) adding an acid to said vessel, with or without stirring and with or without addition of water, to adjust the pH to from about 7 to about 8;
• (III) optionally, adding a surfactant to said vessel, with or without stirring and with or without addition of water, and
• (IV) optionally, adding water to said vessel to generate an As2O3 solution with or without stirring;
• and
• (B) lyophilizing said As2O3 solution comprising the steps of:
• (V) freezing said As2O3 solution to generate a frozen As2O3 product;
• and
• (VI) drying said As2O3 product to generate said lyophilized composition comprising arsenic.

A method for providing oral bioavailability of arsenic to a subject, wherein said oral bioavailability is in the range of from about 50% to about 100% of that of the intravenous administration of a pharmaceutical composition comprising arsenic, said method comprising the steps of:

• (A) solubilizing As2O3 powder in an aqueous medium to form an As2O3 solution, comprising the steps of:
• (I) adding an alkalizing agent to the As2O3 powder in a vessel, with or without stirring and with or without addition of water, to render a pH of about 12 or higher;
• (II) adding an acid to said vessel, with or without stirring and with or without addition of water, to adjust the pH to from about 7 to about 8;
• (III) optionally, adding a surfactant to said vessel, with or without stirring and with or without addition of water, and
• (IV) optionally, adding water to said vessel to generate an As2O3 solution with or without stirring;
• and
• (B) lyophilizing said As2O3 solution comprising the steps of:
• (V) freezing said As2O3 solution to generate a frozen As2O3 product;
• and
• (VI) drying said As2O3 product to generate said lyophilized composition comprising arsenic.

An oral dosage form in the form of a capsule which weighs 100 units and comprises:

• (I) lyophilized composition comprising arsenic, at an amount that provides 10 units of arsenic trioxide and 5 units sodium lauryl sulfate;
• (II) mannitol at an amount of 73 units;
• (III) talc at an amount of 1;
• and
• (IV) magnesium stearate at an amount of 1 mg;
• which brings the total weight of the composition to 100 units.