Hydrophobic Drug-Delivery Material, Method For Manufacturing Thereof And Methods For Delivery Of A Drug-Delivery Composition

Abstract

A method for manufacturing a drug-delivery composition includes providing at least a pharmaceutically active composition, providing a hydrophobic matrix; and mixing the hydrophobic matrix and the pharmaceutically active composition to form a paste-like or semi-solid drug-delivery composition.

1 - 30 . (canceled) 
     
     
         31 . A method for manufacturing a drug delivery composition, comprising:
 providing an aqueous drug suspension comprising a powder of a pharmaceutically-active macromolecular drug of equal to or greater than 3,000 daltons, selected from the group consisting of a bioactive protein and a nucleic acid, that has been mixed at least with water to obtain the aqueous drug suspension;   providing a hydrophobic matrix comprising, at ambient temperature or at a temperature below ambient but above water-freezing point, a liquid hydrophobic phase or a mixture of a solid hydrophobic phase and a liquid hydrophobic phase selected from the group consisting of wax, ester and oil, wherein the ratio between the solid hydrophobic phase and the liquid hydrophobic phase is greater than or equal to 0 and less than or equal to 20, particularly greater than or equal to 0 and less than or equal to 10;   kneading the hydrophobic matrix and the suspension, at ambient temperature or at a temperature below ambient but above the water-freezing point, to form a paste-like or semi-solid drug delivery composition comprising the pharmaceutically-active macromolecular drug homogeneously distributed as particles throughout the hydrophobic matrix, wherein the drug delivery composition is composed of at least 90 wt % of hydrophobic components, wherein the particles have a mean size between 100 nm and 5 μm;   wherein the kneading comprises performing repeated cycles of pressing and folding, in an algorithmic manner, the hydrophobic matrix and the suspension under partial removal of water from the composition.   
     
     
         32 . A method for manufacturing a drug delivery composition, comprising:
 providing an aqueous drug solution comprising at least water and a pharmaceutically-active macromolecular drug selected from the group consisting of a bioactive protein and a nucleic acid, and water, wherein the weight ratio between water and the drug is greater than or equal to 4:1 and less than or equal to 100:1;   providing a hydrophobic matrix comprising, at ambient temperature or at a temperature below ambient but above the water-freezing point, a liquid hydrophobic phase or a mixture of a solid hydrophobic phase and a liquid hydrophobic phase selected from the group consisting of wax, ester and oil, wherein the ratio between the solid hydrophobic phase and the liquid hydrophobic phase is greater than or equal to 0 and less than or equal to 20, particularly greater than or equal to 0 and less than or equal to 10;   kneading the hydrophobic matrix and the drug solution, at ambient temperature or at a temperature below ambient but above the water-freezing point, so as to form a paste-like or semi-solid drug delivery composition comprising the pharmaceutically-active macromolecular drug homogeneously distributed as particles throughout the hydrophobic matrix, wherein the drug delivery composition is composed of at least 90 wt % of hydrophobic components, and wherein the kneading comprises performing repeated cycles of pressing and folding, in an algorithmic manner, the hydrophobic matrix and the drug solution under partial removal of water from the composition.   
     
     
         33 . A method for manufacturing a drug delivery composition, comprising:
 providing a powder of a pharmaceutically-active macromolecular drug selected from the group consisting of a bioactive protein and a nucleic acid;   providing a hydrophobic matrix comprising, at ambient temperature or at a temperature below ambient but above the water-freezing point, a liquid hydrophobic phase or a mixture of a solid hydrophobic phase and a liquid hydrophobic phase selected from the group consisting of wax, ester and oil, wherein the ratio between the solid hydrophobic phase and the liquid hydrophobic phase is greater than or equal to 0 and less than or equal to 20, particularly greater than or equal to 0 and less than or equal to 10;   kneading the hydrophobic matrix and the powder, at ambient temperature or at a temperature below ambient but above the water-freezing point, to form a paste-like or semi-solid drug delivery composition comprising the pharmaceutically-active macromolecular drug homogeneously distributed throughout the hydrophobic matrix, wherein the drug delivery composition is composed of at least 90 wt % of hydrophobic components, and wherein the kneading comprises performing repeated cycles of pressing and folding, in an algorithmic manner, the hydrophobic matrix and the powder.   
     
     
         34 . A dosage form, comprising:
 a drug delivery composition comprising
 a hydrophobic matrix comprising, at ambient temperature or at a temperature below ambient but above the water-freezing point, a liquid hydrophobic phase or a mixture of a solid hydrophobic phase and a liquid hydrophobic phase selected from the group consisting of wax, ester and oil, wherein the ratio between the solid hydrophobic phase and the liquid hydrophobic phase is greater than or equal to 0 and less than or equal to 20, particularly greater than or equal to 0 and less than or equal to 10; 
 a pharmaceutically-active macromolecular drug selected from the group consisting of a bioactive protein and a nucleic acid, wherein the pharmaceutically-active macromolecular drug is homogeneously distributed as particles throughout the hydrophobic matrix, the particles having a mean size between 100 nm and 5 μm; 
 the drug delivery composition being liquid, paste-like or semi-solid and composed of at least 90 wt % of hydrophobic components formed by the hydrophobic matrix; 
   the dosage form having a size and shape suitable for injection into a human or mammalian eye.   
     
     
         35 . The method according to  claim 33 , wherein the powder of the pharmaceutically-active composition comprises particles in a size range from about 100 nm to about 50 μm. 
     
     
         36 . The drug-delivery composition according to  claim 32 , wherein the pharmaceutically active compound is dissolved in a solution comprising water, electrolytes and at least one of monosaccharides, disaccharides, oligosaccharides, polysaccharides like hyaluronic acid, pectin, gum arabic and other gums, albumin, chitosan, collagen, collagen-n-hydroxysuccinimide, fibrin, fibrinogen, gelatin, globulin, polyaminoacids, polyurethane comprising amino acids, prolamin, protein-based polymers, copolymers and derivatives thereof, and mixtures thereof. 
     
     
         37 . The method according to any of the  claims 31  to  33 , wherein the hydrophobic solid component is selected from waxes, fruit wax, carnauba wax, bees wax, waxy alcohols, plant waxes, soybean waxes, synthetic waxes, triglycerides, lipids, long-chain fatty acids and their salts like magnesium stearate, magnesium palmitate, esters of long-chain fatty acids, long-chain alcohols like cetyl palmitate, waxy alcohols, long-chain alcohols like cetylalcohol, oxethylated plant oils, oxethylated fatty alcohols, and
 wherein the liquid hydrophobic component is selected from plant oils, castor oil, jojoba oil, soybean oil, silicon oils, paraffin oils, and mineral oils, cremophor, oxethylated plant oils, oxethylated fatty alcohols, tocopherols, lipids, phospholipids.