Powder for oral suspension containing tadalafil

Abstract

This document discloses a powder formulation of tadalafil for oral administration. Also disclosed are a method of preparing the powder formulation, a suspension dosage form of tadalafil and a method of treating diseases.

1 - 43 . (canceled) 
     
     
         44 . A method of achieving in a subject a selected area under curve (AUC 0-inf) from a tadalafil suspension, comprising reconstituting a powder formulation into the suspension and administering to the subject the suspension,
 wherein the ratio between the AUC from the suspension and the AUC from an in immediate release tadalafil tablet form with the same dose ranges from about 0.8 to about 1.25,   wherein the ratio between maximum tadalafil plasma concentration (C max ) to average plasma concentration (C ave ) ranging from about 1.4 to about 1.9,   wherein the powder formulation comprises:   tadalafil or a pharmaceutically acceptable salt thereof;   a suspending agent, wherein the suspending agent is in an amount ranging from about 0.1% to about 10% w/w in the powder formulation; and   one or more pharmaceutically acceptable excipients.   
     
     
         45 . The method formulation of  claim 44 , wherein the suspending agent, the one or more pharmaceutically acceptable excipients, and their respective amounts are selected so that the suspension provides an in vitro release of at least 75% of the tadalafil within about 10 minutes under USP dissolution apparatus 2 in 1000 ml of 0.5% SLS at 50 rpm. 
     
     
         46 . The method formulation of  claim 44 , wherein the suspending agent, the one or more pharmaceutically acceptable excipients, and their respective amounts are selected so that the ratio between the AUC from the suspension and the AUC from the in immediate release tadalafil tablet form with the same dose ranges from about 0.9 to about 1.1. 
     
     
         47 . The method formulation of  claim 44 , wherein the suspending agent, the one or more pharmaceutically acceptable excipients, and their respective amounts are selected so that the ratio between the C max  of the tadalafil suspension and a Cmax of the immediate release tablet form ranges from about 0.7 to about 1.20. 
     
     
         48 . The method formulation of  claim 44 , wherein the suspending agent, the one or more pharmaceutically acceptable excipients, and their respective amounts are selected so that the ratio between a maximum tadalafil plasma concentration (C max ) of the tadalafil suspension and a C max  of the immediate release tablet form ranges from about 0.9 to about 1.1. 
     
     
         49 . The method formulation of  claim 44 , wherein the suspending agent, the one or more pharmaceutically acceptable excipients, and their respective amounts are selected so that the ratio between C max  to average plasma concentration (C ave ) ranging from about 1.45 to about 1.65. 
     
     
         50 . The method formulation of  claim 44 , wherein the suspending agent, the one or more pharmaceutically acceptable excipients, and their respective amounts are selected so that the ratio between minimum tadalafil plasma concentration (C min ) to C ave  ranging from about 0.6 to about 0.8. 
     
     
         51 . The method of  claim 44 , wherein the powder formulation further comprises a glidant ranging from about 1% to about 3.5% by weight of the powder formulation. 
     
     
         52 . The method formulation of  claim 51 , where the glidant is silicon dioxide. 
     
     
         53 . The method formulation of  claim 44 , further comprising a diluent selected from the group consisting of sucrose, dextrose, mannitol, sorbitol, maltitol, starch, lactose, microcrystalline cellulose, and any combination thereof, wherein the diluent ranges from about 10% to about 98% by weight of the powder formulation. 
     
     
         54 . The method formulation of  claim 44 , which further comprises sorbitol ranging from about 50% to about 85% by weight in the powder formulation. 
     
     
         55 . The method formulation of  claim 44 , which further comprises sorbitol ranging from about 70% to about 85%. 
     
     
         56 . The method of  claim 44 , wherein the suspending agent is in an amount ranging from about 1% to about 5% w/w in the powder formulation. 
     
     
         57 . The method formulation of  claim 44 , wherein the tadalafil or the pharmaceutically acceptable salt thereof and the suspending agent have a ratio ranging from about 10:1 to about 5:8 by weight. 
     
     
         58 . The method formulation of  claim 44 , wherein the tadalafil or the pharmaceutically acceptable salt thereof and the suspending agent have a ratio of about 5:4 by weight. 
     
     
         59 . The method formulation of  claim 44 , wherein the suspending agent is selected from the group consisting of hydrocolloid gum, cellulosic derivative, a polysaccharide, alginate, acrylic acid copolymer, Polyvinylpyrrolidone, aluminiummagnesium silicate, and any combination thereof. 
     
     
         60 . The method formulation of  claim 44 , wherein the suspending agent is hydrocolloid gum. 
     
     
         61 . The method formulation of  claim 44 , wherein the suspending agent and its amount are selected so that the reconstituted suspension maintains a sedimentation ratio of more than 0.9 in a sitting, non-stirred condition for at least 24 hours. 
     
     
         62 . The method formulation of  claim 44 , wherein the suspending agent, the one or more pharmaceutically acceptable excipients, and their respective amounts are selected so that the suspension prepared from the powder formulation provides a release of the tadalafil bioequivalent to the same dose of tadalafil in immediate release tablet form. 
     
     
         63 . The method formulation of  claim 44 , wherein the subject has been diagnosed with erectile dysfunction, enlarged prostate, pulmonary arterial hypertension, heart failure, hypertension, left ventricle diastolic dysfunction, scleroderma spectrum of disease, systemic sclerosis, fetal growth restriction, skeletal muscle and perceptual fatigue, interstitial lung disease of scleroderma, chronic obstructive pulmonary disease, duchenne muscular dystrophy.