Oral suspension of prednisolone acetate

Abstract

The present invention relates to novel oral suspension formulation comprising prednisolone acetate, a pharmaceutically acceptable vehicle and a thickening agent. The present invention further provides a method of treating patients in need of prednisolone with the novel formulation.

1 - 23 . (canceled) 
     
     
         24 . A pharmaceutical composition comprising a pharmaceutically effective amount of fine milled prednisolone acetate particles dispersed in suspension in the composition, wherein the composition is suitable for oral delivery and comprises a thickening agent and a wetting agent. 
     
     
         25 . The composition of  claim 24 , wherein the prednisolone acetate remains dispersed in the suspension without agitation during the shelf life of the composition and has a crystalline stability such that the prednisolone particles stay within a target particle size range over time. 
     
     
         26 . The composition of  claim 24 , wherein the composition is spill-resistant. 
     
     
         27 . The composition of  claim 24 , wherein the pH is between about 4.0 and about 5.9. 
     
     
         28 . The composition of  claim 24 , wherein the pH is between about 4.6 and about 5.4. 
     
     
         29 . The composition of  claim 24 , wherein the composition comprises components that are mutually compatible. 
     
     
         30 . The composition of  claim 24 , wherein the composition is storage-stable. 
     
     
         31 . The composition of  claim 24 , wherein the thickening agent is a carbomer. 
     
     
         32 . The composition of  claim 24 , wherein the wetting agent is a poloxamer. 
     
     
         33 . The composition of  claim 24 , wherein the composition comprises an aqueous vehicle. 
     
     
         34 . The pharmaceutical composition of  claim 24 , wherein the composition, when administered to humans, exhibits pharmacokinetic parameters within the 80-125% confidence interval, with a statistical power of at least 80%, of one or more of the following values:
 a. C max  of 176.27 ng/mL;   b. T max  of 1.00 hour;   c. AUC T  of 812.39 ng·h/mL;   d. AUC ∞  of 846.53 ng·h/mL;   e. K el  of 0.2629 hr −1 ; and   f. T 1/2el  of 2.66 hours.   
     
     
         35 . The pharmaceutical composition of  claim 24 , comprising from about 0.5 mg/mL to about 5 mg/mL of prednisolone acetate. 
     
     
         36 . The pharmaceutical composition of  claim 24 , comprising from about 0.5 mg/mL to about 5 mg/mL of prednisolone acetate, water, glycerin, sorbitol in an amount up to about 20% (w/w), propylene glycol in an amount up to about 20% (w/w), wetting agent in an amount up to about 3% (w/w) and a thickening agent in an amount up to about 1% (w/w). 
     
     
         37 . The pharmaceutical composition of  claim 24 , comprising:
 a. from about 5 mg/5 mL to about 15 mg/5 mL prednisolone acetate;   b. 0.1% poloxamer 188;   c. 50% glycerin;   d. 5% sorbitol crystalline;   e. 5% propylene glycol;   f. 0.065% edetate disodium;   g. 0.2% sucralose;   h. carbomer in an amount up to about 1%;   i. 0.04% butylparaben; and   j. sodium hydroxide.   
     
     
         38 . The pharmaceutical composition of  claim 24 , wherein the composition exhibits an in vitro dissolution profile of about 82% to about 85% released after about 15 minutes, about 93% to about 95% released after about 30 minutes, about 95% to about 97% released after about 45 minutes and about 96% to about 97% released after about 60 minutes. 
     
     
         39 . A method for treating a patient in need of prednisolone, comprising the step of orally administering a therapeutically effective amount of the pharmaceutical composition of  claim 24 . 
     
     
         40 . The method of  claim 39 , wherein the patient is suffering from a medical condition selected from the group consisting of endocrine disorders, rheumatic disorders, collagen diseases, dermatologic diseases, allergic states, respiratory diseases, hematologic disorders, neoplastic diseases, edema, gastrointestinal diseases and nervous diseases.