Mirtazapine Solid Dosage Forms

Abstract

A non-effervescent, solid dosage form containing mirtazapine, which is used to form mirtazapine pharmaceutical tablets. The dosage form contains mirtazapine, a hydrophilic component, and at least one lubricant. In some embodiments, the dosage forms contain a salivating agent. Processes for producing mirtazapine orally disintegrating tablets are also provided.

1 - 41 . (canceled) 
     
     
         42 . A method of treating neurological disorders and diseases which comprises administering a non-effervescent, orally disintegrating mirtazapine tablet comprising:
 i) about 0.5% to about 10% of mirtazapine;   ii) about 35% to about 65% by weight of water-soluble carbohydrate selected from the group consisting of mannitol, xylitol, sorbitol, sucrose and combinations thereof;   iii) about 15% to about 35% by weight of a disintegrating agent selected from the group consisting of crospovidone, croscarmelose sodium, sodium starch glycolate and combinations thereof;   iv) about 5% to about 15% by weight of microcrystalline cellulose;   v) about 0.5% to about 4% by weight of at least one lubricant;   vi) 0 to about 10% by weight of a salivating agent;   vii) optionally a coloring agent;   viii) optionally a flavoring agent; and   ix) optionally a sweetener.   
     
     
         43 - 51 . (canceled) 
     
     
         52 . The method of  claim 42  wherein the tablet comprises 15 mg, 30 mg or 45 mg of mirtazapine and exhibits a hardness of about 1.5 kp to about 3 kp, a hardness greater than 1.0 kp after exposure for 24 hours at 25° C. and 60% relative humidity and greater than about 0.8 kp after exposure for 60 minutes at 40° C. and 75% relative humidity. 
     
     
         53 . The method according to  claim 42  wherein the tablet disintegrates in about 3 to about 8 seconds. 
     
     
         54 . The method of  claim 42  wherein the hardness of the tablet is about 2 kp to about 3 kp. 
     
     
         55 . The method of  claim 42  wherein the tablet comprises:
 i) about 0.5% to about 10% by weight of mirtazapine; 
 ii) about 35% to about 65% by weight of mannitol; 
 iii) about 15% to about 35% by weight of crospovidone; 
 iv) about 5% to about 15% by weight of microcrystalline cellulose; 
 v) about 0.5% to about 4% by weight of at least one lubricant; 
 vi) 0 to about 10% by weight of a salivating agent; 
 vii) colloidal silicon dioxide; 
 viii) optionally a coloring agent; 
 xi) optionally a flavoring agent; and 
 x) optionally a sweetener. 
 
     
     
         56 . The method of  claim 55  wherein the tablet comprises 15 mg, 30 mg or 45 mg of mirtazapine and exhibits a hardness of about 1.5 kp to about 3 kp, a hardness greater than 1.0 kp after exposure for 24 hours at 25° C. and 60% relative humidity and greater than about 0.8 kp after exposure for 60 minutes at 40° C. and 75% relative humidity. 
     
     
         57 . A method of treating neurological disorders and diseases which comprises administering a non-effervescent, orally disintegrating mirtazapine tablet prepared by a method consisting of:
 a) preparing a dry mixture consisting of:   i) about 0.5% to about 10% by weight of mirtazapine;   ii) about 35% to about 65% by weight of water-soluble carbohydrate selected from the group consisting of mannitol, xylitol, sorbitol, sucrose and combinations thereof;   iii) about 15% to about 35% by weight of a disintegrating agent selected from the group consisting of crospovidone, croscarmelose sodium, sodium starch glycolate and combinations thereof;   iv) about 5 to about 15% by weight of microcrystalline cellulose;   v) about 0.5% to about 4% by weight of at least one lubricant;   vi) 0 to about 10% by weight of a salivating agent;   vii) optionally a coloring agent;   viii) optionally a flavoring agent; and   ix) optionally a sweetener; and   b) compressing the dry mixture into 15 mg, 30 mg or 45 mg mirtazapine tablets.   
     
     
         58 . The method of  claim 57  wherein the tablet exhibits a hardness of about 1.5 kp to about 3 kp, a hardness greater than 1.0 kp after exposure for 24 hours at 25° C. and 60% relative humidity and greater than about 0.8 kp after exposure for 60 minutes at 40° C. and 75% relative humidity. 
     
     
         59 . The method according to  claim 57  wherein the tablet disintegrates in about 3 to about 8 seconds. 
     
     
         60 . The method of  claim 57  wherein the hardness of the tablet is about 2 kp to about 3 kp. 
     
     
         61 . The method of  claim 57  wherein the orally disintegrating mirtazapine tablet is prepared by a method consisting of:
 a) preparing a dry mixture consisting of: 
 i) about 0.5% to about 10% by weight of mirtazapine; 
 ii) about 35% to about 65% by weight of mannitol; 
 iii) about 15% to about 35% by weight of crospovidone; 
 iv) about 5 to about 15% by weight of microcrystalline cellulose; 
 v) about 0.5% to about 4% by weight of at least one lubricant; 
 vi) 0 to about 10% by weight of a salivating agent; 
 vii) colloidal silicon dioxide; 
 viii) optionally a coloring agent; 
 xi) optionally a flavoring agent; and 
 x) optionally a sweetener.