Amorphous substance of tricyclic triazolobenzazepine derivative
View Patent ↗Disclosed are 2-(1-isopropoxycarbonyloxy-2-methylpropyl)-7,8-dimethoxy-4(5 H ), 10-dioxo-2 H -1,2,3-triazolo[4,5-c][1]benzazepine, which has been rendered amorphous and possesses improved absorption and dissoluvability, and a pharmaceutical composition comprising the same. Also disclosed are processes for producing 2-(1-isopropoxycarbonyloxy-2-methylpropyl)-7,8-dimethoxy-4(5 H ), 10-dioxo-2 H -1,2,3-triazolo[4,5-c][1]benzazepine, which has been rendered amorphous, and a pharmaceutical composition comprising the same.
1. A composition comprising an amorphous compound 2-(1-isopropoxy-carbonyloxy-2-methylpropyl)-7, 8-dimethoxy-4(5H), 10-dioxo-2H-1,2,3-triazolo[4,5-c][1]benzazepine having no diffraction peak in a powder X-ray diffraction pattern and a solubility of 15 to 20 μg/mL in a 1 wt % methylcellulose solution at 37° C. and methylcellulose and/or hydroxypropylmethylcellulose.
2. The composition according to claim 1 , wherein the mixing ratio of the amorphous compound of 2-(1-isopropoxy-carbonyloxy-2-methylpropyl )-7,8-dimethoxy-4(5H), 10-dioxo-2H-1,2,3-triazolo[4,5-c][1]benzazepine to the total amount of methylcellulose and/or hydroxypropylmethylcellulose is in the range of 1:0.01 to 2.
3. A composition comprising 2-(1-isopropoxy-carbonyloxy-2-methylpropyl)-7,8-dimethoxy-4(5H), 10-dioxo-2H-1,2,3-triazolo[4,5-c][1]benzazepine having no diffraction peak in a powder X-ray diffraction pattern and a solubility of 15 to 20 μg/mL in a 1 wt % methylcellulose solution at 37° C. and a polymer compound, wherein the polymer compound is one or at least two compounds selected from the group consisting of ethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylcellulose, carboxymethylethylcellulose, polyvinyl pyrrolidone, polyvinyl acetal diethylaminoacetate, methacrylic acid copolymer L, aminoalkyl methacryl acrylate copolymer E, and vinyl acetate-vinylpyrrolidone copolymer.
4. A process for producing the composition according to claim 1 , said process comprising the steps of: dissolving 2-(1-isopropoxycarbonyloxy -2-methylpropyl )-7,8-dimethoxy-4(5H), 10-dioxo-2H-1,2,3-triazolo [4,5-c][1]benzazepine and methylcellulose and/or hydroxypropylmethylcellulose in methylene chloride to prepare a solution; and then spray-drying the solution.
5. A process for producing the composition according to claim 3 , said process comprising the steps of: dissolving 2-(1-isopropoxycarbonyloxy-2-methylpropyl)-7,8-dimethoxy-4(5H), 10-dioxo-2H-1,2,3-triazolo[4,5-c][1]benzazepine and the polymer compound in methylene chloride or a methylene chloride/lower alcohol mixed solvent to prepare a solution; and then spray-drying the solution.
6. The process according to claim 5 , wherein the lower alcohol is an alkyl alcohol having 1 to 3 carbon atoms.
7. A pharmaceutical composition for oral administration, comprising the composition according to claim 1 and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition for oral administration, comprising the composition according to claim 2 and a pharmaceutically acceptable carrier.
9. A pharmaceutical composition for oral administration, comprising the composition according to claim 3 and a pharmaceutically acceptable carrier.
10. A method for treating an allergic disease, wherein said method comprises the step of administering the composition according to claim 1 to an animal.
11. A method for treating an allergic disease, wherein said method comprises the step of administering the composition according to claim 2 to an animal.
12. A method for treating an allergic disease, wherein said method comprises the step of administering the composition according to claim 3 to an animal.
13. The method of any one of claims 10 - 12 wherein said animal is a human.