Composition and method for administration of pharmaceutically active substances

A method of administering a particulate suspension of a pharmaceutically active substance which is substantially free of water, comprising applying to a mucosal body surface a particulate composition comprising:

• (a) a medically effective amount of a pharmaceutically active substance;
• and
• (b) a biocompatible steroid of the formula ##STR4## wherein a dashed line represents a single or double bond;
• D represents a group having a molecular weight below 600 daltons which renders an effective amount of said steroid water soluble within the range of about pH 2 to about pH 12;
• E represents OAc, OH, a lower alkyl group or a lower heteroalkyl group;
• G represents OAc, OH, a lower alkyl group or a lower heteroalkyl group;
• W represents OAc or H;
• and
• Q, V, and X individually, represent OH or H, said steroid (i) containing two to three polar functions, exclusive of the function represented by D;
• and (ii) being capable of increasing the permeation of a human or animal mucosal surface by a pharmaceutically active substance, in a amount effective to increase the permeability of said body surface to a pharmaceutically active substance,
• wherein said composition is delivered to the body surface by means of a biocompatible (hydro/fluoro) carbon aerosol propellant.

A method of preparing a composition for the administration of a pharmaceutically active substance comprising:

• (a) preparing an aqueous solution containing
• (i) a biocompatible, amphiphilic steroid of the formula:
• ##STR6## wherein a dashed line represents a single or a double bond;
• D represents a group having a molecular weight below 600 daltons which renders an effective amount of said steroid water soluble within the range of about pH 2 to about pH 12;
• E represents OAc, OH, a lower alkyl group or a lower heteroalkyl group;
• G represents OAc, OH, a lower alkyl group or a lower heteroalkyl group;
• W represents oAc or H;
• and
• Q, V and X, each individually, represent OH or H,
• said steroid (i) containing two to three polar functions, exclusive of the function represented by D;
• and (ii) being capable of increasing the permeation of a human or animal mucosal surface by a pharmaceutically active substance in an amount effective to increase the permeability of said body surface to a pharmaceutically active substance;
• and
• (ii) a medically effective amount of a pharmaceutically active substance;
• (b) removing the water from the solution by lyophilization;
• (c) sizing the lyophilized composition to a particle size from about 2 microns to about 45 microns;
• and
• (d) adding the lyophilized particulate to a normally-gaseous (hydro/fluoro)carbon propellant under sufficient pressure that the propellant is in liquid form.

A composition for the administration of a pharmaceutically active a polypeptide drug, the composition comprising a lyophilized powder formulation of:

• (a) a medically effective amount of the polypeptide drug and
• (b) a biocompatible steroid of the formula ##STR8## wherein a dashed line represents a single or double bond;
• D represents a group having a molecular weight below 600 daltons which renders an effective amount of said steroid water-soluble within the range of about pH 2 to about pH 12;
• E represents OAc, OH, a lower alkyl group or a lower heteroalkyl group;
• G represents OAc, OH, a lower alkyl group or a lower heteroalkyl group;
• W represents OAc or H;
• and
• Q, V and X, each individually, represent OH or H, said steroid (i) containing two to three polar functions, exclusive of the function represented by D;
• and (ii) being capable of increasing the permeation of a human or animal mucosal surface by a pharmaceutically active substance, in an amount effective to increase the permeability of said body surface to a pharmaceutically active substance;
• and
• wherein said particulate suspension is suspended in a biocompatible (hydro/fluoro) carbon propellant.