US 11,752,104 B2
Oral composition and methods for manufacturing the same and treatment
Meng-Kun Tsai, Taipei (TW); Chih-Chiang Yang, New Taipei (TW); Wen-Che Wang, New Taipei (TW); Tzu-Yu Chien, New Taipei (TW); Chien-Chia Wu, New Taipei (TW); and Lai-Cheng Chin, New Taipei (TW)
Assigned to MEDICAL AND PHARMACEUTICAL INDUSTRY TECHNOLOGY AND, New Taipei (TW)
Filed by MEDICAL AND PHARMACEUTICAL INDUSTRY TECHNOLOGY AND DEVELOPMENT CENTER, New Taipei (TW)
Filed on May 29, 2020, as Appl. No. 16/887,259.
Claims priority of provisional application 62/854,969, filed on May 31, 2019.
Prior Publication US 2020/0375901 A1, Dec. 3, 2020
Int. Cl. A61K 9/16 (2006.01); A61K 31/717 (2006.01); A61K 31/436 (2006.01); A61K 9/00 (2006.01)
CPC A61K 9/167 (2013.01) [A61K 9/0053 (2013.01); A61K 31/436 (2013.01); A61K 31/717 (2013.01)] 16 Claims
 
1. A method for manufacturing an oral composition comprising
milling a first portion of an active ingredient in a water solution with an addition of a first portion of a hydrophilic dispersant comprising d-α-Tocopheryl polyethylene glycol 1000 succinate to form a first portion of a milled active ingredient having a particle size of D90 of 100 nm to 3000 nm;
mixing the first portion of the milled active ingredient with a filler and the first portion of the hydrophilic dispersant in liquid phase to form a liquid precursor;
drying the liquid precursor to form an immediate-release pharmaceutical powder;
milling a second portion of the active ingredient in the water solution with the addition of a second portion of the hydrophilic dispersant comprising d-α-Tocopheryl polyethylene glycol 1000 succinate to form a second portion of the milled active ingredient having the particle size of D90 of 100 nm to 3000 nm;
mixing the second portion of the milled active ingredient with the filler and the second portion of the hydrophilic dispersant in liquid phase to form a liquid mixture;
drying the liquid mixture to form an extended-release pharmaceutical pre-admixture;
mixing a controlled-release material with the extended-release pharmaceutical pre-admixture to form an extended-release pharmaceutical admixture; and
mixing the extended-release pharmaceutical admixture with the immediate-release pharmaceutical powder, wherein a weight ratio of the milled active ingredient of the immediate-release pharmaceutical powder to the extended-release pharmaceutical admixture is 2:8 to 4:6,
wherein an immediate-release pharmaceutical admixture comprises the first portion of the milled active ingredient and the first portion of the hydrophilic dispersant, wherein the active ingredient is substantially insoluble in water; and
the extended-release pharmaceutical admixture comprises the controlled-release material, the second portion of the milled active ingredient, and the second portion of the hydrophilic dispersant, wherein the second portion of the milled active ingredient and the second portion of the hydrophilic dispersant are mixed in the controlled-release material,
wherein the milled active ingredient is present as a nanoparticle in the immediate-release pharmaceutical admixture and the extended-release pharmaceutical admixture, and
wherein the milled active ingredient comprises tacrolimus, a dissolution percentage of tacrolimus is about 20% to about 40% within 4 hrs when assayed in 0.005% hydroxypropyl cellulose (HPC) medium in pH 4.5, and the dissolution percentage of tacrolimus is about 75% to 85% within 24 hrs when assayed in 0.005% hydroxypropyl cellulose (HPC) medium in pH 4.5.