Pharmaceutical Composition for Topical Application

Abstract

A pharmaceutical or cosmetic carrier or composition for topical application characterized by rheological properties which render the carrier or composition semi-solid at rest and a liquid upon application of shear forces thereto. The composition or carrier are prepared by mixing 1-25 percent of a solidifying agent and 75-99 percent of a hydrophobic solvent, by weight, wherein at least one of them has therapeutic or cosmetic benefits, in the presence or absence of a biologically active substance.

What is claimed is: 
     
         1 . A pharmaceutical carrier comprising:
 a) about 75% to about 99% by weight of a hydrophobic solvent, and   b) about 1% to about 25% by weight of a solidifying agent, wherein the solidifying agent comprises a fatty alcohol; wherein the solidifying agent is uniformly distributed and the carrier is free of a netted framework.   
     
     
         2 . A pharmaceutical composition, comprising the carrier of  claim 1  and further comprising a therapeutically effective amount of a biologically active substance. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the biologically active substance is selected from the group of consisting of an antibiotic agent, a free radical generating agent, an antifungal agent, an antiviral agent, a non-steroidal anti-inflammatory drug, an immunosuppressant, an antihistamine agent, an anti-inflammatory agent, a retinoid agent, a tar agent, an antipruritics agent, and a scabicide agent. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the antibiotic agent comprises a tetracycline antibiotic. 
     
     
         5 . The pharmaceutical composition of  claim 2 , wherein the hydrophobic solvent comprises an oil selected from the group consisting of olive oil, soybean oil, canola oil, rapeseed oil, cottonseed oil, coconut oil, palm oil, sesame oil, sunflower oil, safflower oil, rice bran oil, borage seed oil,  syzigium aromaticum  oil, hempseed oil, herring oil, cod-liver oil, salmon oil, corn oil, flaxseed oil, wheat germ oil, rape seed oil, evening primrose oil, rosehip oil, tea tree oil,  melaleuca  oil, and jojoba oil. 
     
     
         6 . The pharmaceutical composition of  claim 2 , wherein the hydrophobic solvent comprises an oil selected from the group consisting of marine animal derived oils, terrestrial animal derived oils, mineral oils, silicone oils, and plant-derived oils. 
     
     
         7 . The pharmaceutical composition of  claim 2 , wherein the hydrophobic solvent comprises an oil selected from the group consisting of omega-3 oil and omega-6 oil. 
     
     
         8 . The pharmaceutical composition of  claim 2 , wherein the hydrophobic solvent comprises a silicone oil. 
     
     
         9 . The pharmaceutical composition of  claim 2 , wherein the carrier provides a protective moisture barrier. 
     
     
         10 . The pharmaceutical composition of  claim 2 , wherein upon application of a shear force the composition liquefies, spreads freely, and is non-sticky. 
     
     
         11 . The pharmaceutical composition of  claim 2 , wherein the solidifying agent comprises stearyl alcohol or behenyl alcohol or both. 
     
     
         12 . The pharmaceutical composition of  claim 2 , further comprising a fatty acid having at least 18 carbon atoms in its carbon backbone. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the fatty acid has at least 15 carbon atoms in its carbon backbone. 
     
     
         14 . The pharmaceutical composition of  claim 2 , further comprising an emollient. 
     
     
         15 . The pharmaceutical composition of  claim 2 , wherein the solidifying agent is about 4% to about 12% by weight of the carrier and the hydrophobic solvent is about 88% to about 96% by weight of the carrier. 
     
     
         16 . The pharmaceutical composition of  claim 2 , wherein the carrier is thixotropic. 
     
     
         17 . The pharmaceutical composition of  claim 2 ,
 wherein the solidifying agent is a solid at ambient temperature; and   wherein the biologically active substance comprises a tetracycline antibiotic in a therapeutically effective amount to treat a disease or disorder of the skin or mucosal membrane.   
     
     
         18 . A method of applying a pharmaceutical composition to skin or a mucosal membrane having a disease or disorder, the method comprising administering topically to the skin or mucosal membrane the composition according to  claim 2 ,
 wherein the composition is a semi-solid at rest and liquefies upon application of shear forces thereto; and   wherein upon administration, the composition freely spreads on the skin surface or mucosal membrane and is absorbed.   
     
     
         19 . The method of  claim 18 , wherein the composition spreads without film formation. 
     
     
         20 . The method of  claim 18 , wherein the composition is adapted to facilitate enhanced penetration of the active agent. 
     
     
         21 . The method of  claim 18 , wherein the biologically active agent comprises a tetracycline antibiotic. 
     
     
         22 . The method of  claim 18 , wherein the composition provides a protective moisture barrier. 
     
     
         23 . The method of  claim 18 , wherein the composition is delivered by means of a dermal patch or as a suppository. 
     
     
         24 . A method of preparing a pharmaceutical carrier, the method comprising the steps of:
 (i) warming a hydrophobic solvent and a solidifying agent to a temperature above the melting temperature of the solidifying agent;   (ii) mixing the hydrophobic solvent and the solidifying agent so as to obtain a mixture containing about 75% to about 99% of the hydrophobic solvent by weight of the carrier and about 1% to about 25% of the solidifying agent by weight of the carrier;   (iii) optionally further mixing into the carrier mixture a therapeutically or cosmetically effective amount of a biologically active substance; and   (iv) cooling the mixture;   wherein when a biologically active substance is mixed into the mixture, cooling of the mixture can occur before or after addition of the biologically active substance depending on the temperature sensitivity of the biologically active substance;   wherein the solidifying agent comprises a fatty alcohol; and   wherein the solidifying agent is uniformly distributed and the carrier is free of a netted framework.   
     
     
         25 . A method of treating a disease or disorder of a skin or a mucosal membrane comprising:
 topically administering a pharmaceutical composition to the skin or the mucosal membrane, the pharmaceutical composition comprising, by weight, a mixture of:   about 75% to about 99% of a hydrophobic solvent,   about 1% to about 25% of a solidifying agent, wherein the solidifying agent comprises a fatty alcohol; and   a biologically active agent selected from the group consisting of an antibiotic agent, a free radical generating agent, an antifungal agent, an antiviral agent, a non-steroidal anti-inflammatory drug, an immunosuppressant, an antihistamine agent, an anti-inflammatory agent, a retinoid agent, a tar agent, an antipruritics agent, and a scabicide agent; wherein the antibiotic agent is selected from the group consisting of chloramphenicol, tetracyclines, synthetic and semi-synthetic penicillins, beta-lactams, quinolones, fluoroquinolones, macrolide antibiotics, peptide antibiotics, cyclosporines, erythromycin, and clyndamycin;   wherein the composition is a semi-solid a rest and liquefies upon application of shear forces thereto;   wherein the composition is free of a netted framework of solidifying agent; and   wherein the disease or disorder is selected from the group consisting of psoriasis, acne, seborrhea, seborrheic dermatitis, alopecia, excessive hair growth, ichthyosis, infection, inflammation, wounds, burns, cuts, ulcers, psoriasis, seborrheic dermatitis of the face and trunk, seborrheic blepharitis, contact dermatitis, stasis dermatitis, and exfoliative dermatitis.