Method for the treatment of acne

Abstract

A method for treatment of acne with tetracyclines is provided. A lower sustained dose and no loading dose is employed, with an optional once-a-day dosing regimen.

1 . A method of treating acne vulgaris, comprising the step of: 
 administering to a person suffering from acne vulgaris an oral tetracycline antibiotic in an amount of from about 0.5 to about 1.5 mg per kilogram of body weight, wherein the oral tetracycline antibiotic is contained in a pharmaceutically suitable delivery vehicle.    
     
     
         2 . The method of  claim 1 , wherein the amount of oral tetracycline antibiotic is from about 0.7 to about 1.3 mg per kilogram of body weight.  
     
     
         3 . The method of  claim 1  or  2 , wherein the oral tetracycline antibiotic is administered without a loading dose.  
     
     
         4 . The method of  claim 1  or  2 , wherein the oral tetracycline antibiotic is minocycline.  
     
     
         5 . The method of  claim 3 , wherein the oral tetracycline antibiotic is minocycline.  
     
     
         6 . The method of  claim 4 , wherein the oral tetracycline antibiotic is administered once a day.  
     
     
         7 . The method of  claim 5 , wherein the oral tetracycline antibiotic is administered once a day.  
     
     
         8 . The method of  claim 4 , wherein the delivery vehicle releases the oral tetracycline antibiotic at a rate of: 
 about 30 to about 52% within about 1 hour    about 53 to about 84% within about 2 hours, and    at least about 85% within about 4 hours.    
     
     
         9 . The method of  claim 5 , wherein the delivery vehicle releases the oral tetracycline antibiotic at a rate of: 
 about 30 to about 52% within about 1 hour    about 53 to about 84% within about 2 hours, and    at least about 85% within about 4 hours.    
     
     
         10 . The method of  claim 5 , wherein the delivery vehicle releases the oral tetracycline antibiotic at a rate of: 
 about 25 to about 52% within about 1 hour    about 53 to about 89% within about 2 hours, and    at least about 90% within about 4 hours.    
     
     
         11 . The method of  claim 4 , wherein the delivery vehicle releases the oral tetracycline antibiotic at a rate of: 
 about 25 to about 52% within about 1 hour    about 53 to about 89% within about 2 hours, and    at least about 90% within about 4 hours.    
     
     
         12 . The method of  claim 5 , wherein the delivery vehicle releases the oral tetracycline antibiotic in such a manner that the antibiotic reaches a C max  in the person's blood from about 2.75 to about 4.0 hours after administration.  
     
     
         13 . The method of  claim 12  wherein the C max  is reached from about 3.0 to about 3.75 hours after administration.  
     
     
         14 . The method of  claim 4 , wherein the delivery vehicle releases the oral tetracycline antibiotic in such a manner that the antibiotic reaches a C max  in the person's blood from about 2.75 to about 4.0 hours after administration.  
     
     
         15 . The method of  claim 14  wherein the C max  is reached from about 3.0 to about 3.75 hours after administration.  
     
     
         16 . The method of  claim 5 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.3 to about 0.5.  
     
     
         17 . The method of  claim 5 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.35 to about 0.45.  
     
     
         18 . The method of  claim 5 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.36 to about 0.40.  
     
     
         19 . The method of  claim 4 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.3 to about 0.5.  
     
     
         20 . The method of  claim 4 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.35 to about 0.45.  
     
     
         21 . The method of  claim 4 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.36 to about 0.40.  
     
     
         22 . The method of  claim 6 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.3 to about 0.5.  
     
     
         23 . The method of  claim 6 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.35 to about 0.45.  
     
     
         24 . The method of  claim 6 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.36 to about 0.40.  
     
     
         25 . The method of  claim 7 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.3 to about 0.5.  
     
     
         26 . The method of  claim 7 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.35 to about 0.45.  
     
     
         27 . The method of  claim 7 , wherein a ratio of fast dissolving carriers to slow dissolving carriers in the delivery vehicle is from about 0.36 to about 0.40.  
     
     
         28 . An oral dosage form comprising: 
 an oral tetracycline antibiotic;    a fast dissolving carrier; and    a slow dissolving carrier;    wherein the fast dissolving carrier and the slow dissolving carrier are at a weight ratio of 0.3 to 0.5 of fast dissolving carrier to slow dissolving carrier.    
     
     
         29 . The oral dosage form of  claim 28 , wherein the ratio of fast dissolving carrier to slow dissolving carrier is 0.35 to 0.45.  
     
     
         30 . The oral dosage form of  claim 28 , wherein the ratio of fast dissolving carrier to slow dissolving carrier is 0.36 to 0.40.  
     
     
         31 . The oral dosage form of  claim 28 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         32 . The oral dosage form of  claim 29 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         33 . The oral dosage form of  claim 30 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         34 . The oral dosage form of  claim 28 , wherein the fast dissolving carrier comprises lactose monohydrate.  
     
     
         35 . The oral dosage form of  claim 29 , wherein the fast dissolving carrier comprises lactose monohydrate.  
     
     
         36 . The oral dosage form of  claim 30 , wherein the fast dissolving carrier comprises lactose monohydrate.  
     
     
         37 . The oral dosage form of  claim 28 , wherein the slow dissolving carrier comprises HPMC.  
     
     
         38 . The oral dosage form of  claim 29 , wherein the slow dissolving carrier comprises HPMC.  
     
     
         39 . The oral dosage form of  claim 30 , wherein the slow dissolving carrier comprises HPMC.  
     
     
         40 . The oral dosage form of  claim 28 , wherein: 
 the fast dissolving carrier comprises lactose monohydrate; and    the slow dissolving carrier comprises HPMC.    
     
     
         41 . The oral dosage form of  claim 29 , wherein: 
 the fast dissolving carrier comprises lactose monohydrate; and    the slow dissolving carrier comprises HPMC.    
     
     
         42 . The oral dosage form of  claim 30 , wherein: 
 the fast dissolving carrier comprises lactose monohydrate; and    the slow dissolving carrier comprises HPMC.    
     
     
         43 . The oral dosage form of  claim 40 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         44 . The oral dosage form of  claim 41 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         45 . The oral dosage form of  claim 42 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         46 . The oral dosage form of  claim 28 , wherein the slow dissolving carrier is present at about 23.5% to about 27.0% by weight of the oral dosage form.  
     
     
         47 . The oral dosage form of  claim 29 , wherein the slow dissolving carrier is present at about 23.5% to about 27.0% by weight of the oral dosage form.  
     
     
         48 . The oral dosage form of  claim 30 , wherein the slow dissolving carrier is present at about 23.5% to about 27.0% by weight of the oral dosage form.  
     
     
         49 . The oral dosage form of  claim 28 , wherein the slow dissolving carrier is present at: 
 23.5% by weight of the oral dosage form when the oral dosage form comprises 135 mg of the oral tetracycline antibiotic; or    27.0% by weight of the oral dosage form when the oral dosage form comprises 45 mg of the oral tetracycline antibiotic.    
     
     
         50 . The oral dosage form of  claim 29 , wherein the slow dissolving carrier is present at: 
 23.5% by weight of the oral dosage form when the oral dosage form comprises 135 mg of the oral tetracycline antibiotic; or    27.0% by weight of the oral dosage form when the oral dosage form comprises 45 mg of the oral tetracycline antibiotic.    
     
     
         51 . The oral dosage form of  claim 30 , wherein the slow dissolving carrier is present at: 
 23.5% by weight of the oral dosage form when the oral dosage form comprises 135 mg of the oral tetracycline antibiotic; or    27.0% by weight of the oral dosage form when the oral dosage form comprises 45 mg of the oral tetracycline antibiotic.    
     
     
         52 . The oral dosage form of  claim 28 , which is formulated to release the oral tetracycline antibiotic at a rate of: 
 30 to 52% within 1 hour;    53 to 84% within 2 hours; and    at least 85% in 4 hours.    
     
     
         53 . The oral dosage form of  claim 29 , which is formulated to release the oral tetracycline antibiotic at a rate of: 
 30 to 52% within 1 hour;    53 to 84% within 2 hours; and    at least 85% within 4 hours.    
     
     
         54 . The oral dosage form of  claim 30 , which is formulated to release the oral tetracycline antibiotic at a rate of: 
 30 to 52% within 1 hour;    53 to 84% within 2 hours; and    at least 85% within 4 hours.    
     
     
         55 . The oral dosage form of  claim 28 , wherein the oral dosage form is formulated to release the oral tetracycline antibiotic at a rate of: 
 25 to 52% within 1 hour;    53 to 89% within 2 hours; and    at least 90% within 4 hours.    
     
     
         56 . The oral dosage form of  claim 29 , wherein the oral dosage form is formulated to release the oral tetracycline antibiotic at a rate of: 
 25 to 52% within 1 hour;    53 to 89% within 2 hours; and    at least 90% within 4 hours.    
     
     
         57 . The oral dosage form of  claim 30 , wherein the oral dosage form is formulated to release the oral tetracycline antibiotic at a rate of: 
 25 to 52% within 1 hour;    53 to 89% within 2 hours; and    at least 90% within 4 hours.    
     
     
         58 . The oral dosage form of  claim 28 , wherein the oral dosage form is formulated to release the oral tetracycline antibiotic in such a manner that C max  is reached at about 3.0 to about 3.75 hours after administration.  
     
     
         59 . The oral dosage form of  claim 29 , wherein the oral dosage form is formulated to release the oral tetracycline antibiotic in such a manner that C max  is reached at about 3.0 to about 3.75 hours after administration.  
     
     
         60 . The oral dosage form of  claim 30 , wherein the oral dosage form is formulated to release the oral tetracycline antibiotic in such a manner that C max  is reached at about 3.0 to about 3.75 hours after administration.  
     
     
         61 . The oral dosage form of  claim 28 , wherein the oral dosage form is a tablet or caplet comprising 40 mg or 135 mg of the oral tetracycline antibiotic.  
     
     
         62 . The oral dosage form of  claim 61 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         63 . The oral dosage form of  claim 62 , wherein: 
 the fast dissolving carrier comprises lactose monohydrate; and    the slow dissolving carrier comprises HPMC.    
     
     
         64 . An oral dosage form comprising: 
 135 mg of an oral tetracycline antibiotic; and    23.5% by weight HPMC;    wherein the oral dosage form is formulated to release the oral tetracycline antibiotic at a rate of: 
 25 to 52% within 1 hour;  
 53 to 89% within 2 hours; and  
 at least about 90% of the oral tetracycline antibiotic within 4 hours.  
   
     
     
         65 . The oral dosage form of  claim 64 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         66 . The oral dosage form of  claim 64 , which is a tablet or caplet.  
     
     
         67 . A method of treating acne vulgaris comprising: 
 administering to the patient with acne vulgaris an effective amount of an oral dosage form selected from: 
 (A) an oral dosage form comprising:  
 an oral tetracycline antibiotic;  
 a fast dissolving carrier; and  
 a slow dissolving carrier;  
 wherein the fast dissolving carrier and the slow dissolving carrier are at a weight ratio of 0.3 to 0.5; and  
 (B) an oral dosage form comprising:  
 135 mg of an oral tetracycline antibiotic; and  
 23.5% by weight HPMC;  
 wherein the oral dosage form is formulated to release the oral tetracycline antibiotic at a rate of:  
 25 to 52% within 1 hour;  
 53 to 89% within 2 hours; and  
 at least about 90% within 4 hours.  
   
     
     
         68 . The method of  claim 67 , further comprising determining the weight of the patient to calculate the effective amount of the oral dosage form.  
     
     
         69 . The method of  claim 68 , wherein the oral dosage form is formulated to provide the patient with about 0.5 to about 1.5 mg/kg/day of the oral tetracycline antibiotic.  
     
     
         70 . The method of  claim 68 , wherein the oral dosage form is formulated to provide the patient with about 0.7 to about 1.3 mg/kg/day of the oral tetracycline antibiotic.  
     
     
         71 . The method of  claim 68 , wherein the oral dosage form is formulated to provide the patient with about 1.0 mg/kg/day of the oral tetracycline antibiotic.  
     
     
         72 . The method of  claim 67 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         73 . The method of  claim 67 , wherein the oral dosage form is administered once a day.  
     
     
         74 . The method of  claim 67 , wherein the oral dosage form is administered without a loading dose.  
     
     
         75 . The method of  claim 67 , wherein the oral dosage form is (A).  
     
     
         76 . The method of  claim 67 , wherein the oral dosage form is (B).  
     
     
         77 . The method of  claim 67 , wherein the oral tetracycline antibiotic reaches C max  at about 3.0 to about 3.75 hours after administration.  
     
     
         78 . A method of preparing an oral dosage form, comprising combining an oral tetracycline antibiotic with a fast dissolving carrier and a slow dissolving carrier to form a combination, wherein the fast dissolving carrier and the slow dissolving carrier are at a weight ratio of 0.3 to 0.5 of fast dissolving carrier to slow dissolving carrier.  
     
     
         79 . The method of  claim 78 , wherein the weight ratio of fast dissolving carrier to slow dissolving carrier is 0.35 to 0.45.  
     
     
         80 . The method of  claim 78 , wherein the weight ratio of fast dissolving carrier to slow dissolving carrier is 0.36 to 0.40.  
     
     
         81 . The method of  claim 78 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         82 . The method of  claim 79 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         83 . The method of  claim 80 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         84 . The method of  claim 78 , wherein the fast dissolving carrier comprises lactose monohydrate.  
     
     
         85 . The method of  claim 79 , wherein the fast dissolving carrier comprises lactose monohydrate.  
     
     
         86 . The method of  claim 80 , wherein the fast dissolving carrier comprises lactose monohydrate.  
     
     
         87 . The method of  claim 78 , wherein the slow dissolving carrier comprises HPMC.  
     
     
         88 . The method of  claim 79 , wherein the slow dissolving carrier comprises HPMC.  
     
     
         89 . The method of  claim 80 , wherein the slow dissolving carrier comprises HPMC.  
     
     
         90 . The method of  claim 78 , wherein: 
 the fast dissolving carrier comprises lactose monohydrate; and    the slow dissolving carrier comprises HPMC.    
     
     
         91 . The method of  claim 79 , wherein: 
 the fast dissolving carrier comprises lactose monohydrate; and    the slow dissolving carrier comprises HPMC.    
     
     
         92 . The method of  claim 80 , wherein: 
 the fast dissolving carrier comprises lactose monohydrate; and    the slow dissolving carrier comprises HPMC.    
     
     
         93 . The method of  claim 90 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         94 . The method of  claim 91 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         95 . The method of  claim 92 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         96 . The method of  claim 78 , wherein the slow dissolving carrier is present at about 23.5 to about 27.0% by weight of the oral dosage form.  
     
     
         97 . The method of  claim 79 , wherein the slow dissolving carrier is present at about 23.5% to about 27.0% by weight of the oral dosage form.  
     
     
         98 . The method of  claim 80 , wherein the slow dissolving carrier is present at about 23.5% to about 27.0% by weight of the oral dosage form.  
     
     
         99 . The method of  claim 78 , wherein the slow dissolving carrier is present at: 
 23.5% by weight of the oral dosage form when the oral dosage form comprises 135 mg of the oral tetracycline antibiotic; or    27.0% by weight of the oral dosage form when the oral dosage form comprises 45 mg of the oral tetracycline antibiotic.    
     
     
         100 . The method of  claim 79 , wherein the slow dissolving carrier is present at: 
 23.5% by weight of the oral dosage form when the oral dosage form comprises 135 mg of the oral tetracycline antibiotic; or    27.0% by weight of the oral dosage form when the oral dosage form comprises 45 mg of the oral tetracycline antibiotic.    
     
     
         101 . The method of  claim 80 , wherein the slow dissolving carrier is present at: 
 23.5% by weight of the oral dosage form when the oral dosage form comprises 135 mg of the oral tetracycline antibiotic; or    27.0% by weight of the oral dosage form when the oral dosage form comprises 45 mg of the oral tetracycline antibiotic.    
     
     
         102 . The method of  claim 78 , further comprising compressing the combination into a tablet.  
     
     
         103 . The method of  claim 102 , further coating the tablet with Opadry II.  
     
     
         104 . A method of preparing an oral dosage form comprising combining an oral tetracycline antibiotic with 23.5% by weight of HPMC to form a combination, wherein the oral dosage form comprises 135 mg of an oral tetracycline antibiotic and the oral dosage form is formulated to release the oral tetracycline antibiotic at a rate of: 
 25 to 52% within 1 hour;    53 to 89% within 2 hours; and    at least about 90% within 4 hours.    
     
     
         105 . The method of  claim 104 , wherein the oral tetracycline antibiotic is minocycline as hydrochloride.  
     
     
         106 . The method of  claim 104 , further comprising compressing the combination into a tablet.  
     
     
         107 . The method of  claim 106 , further coating the tablet with Opadry II.