US 12,239,691 B2
Formulations for oral administration of active agents
Gregory Burshtein, ModiIn (IL); Ariel Rothner, Jerusalem (IL); Phillip M. Schwartz, Jerusalem (IL); and Hillel Galitzer, Yad Binyamin (IL)
Assigned to Entera Bio Ltd., Jerusalem (IL)
Appl. No. 16/326,213
Filed by Entera Bio Ltd., Jerusalem (IL)
PCT Filed Aug. 17, 2017, PCT No. PCT/IL2017/050920
§ 371(c)(1), (2) Date Feb. 17, 2019,
PCT Pub. No. WO2018/033927, PCT Pub. Date Feb. 22, 2018.
Claims priority of provisional application 62/375,989, filed on Aug. 17, 2016.
Prior Publication US 2019/0209657 A1, Jul. 11, 2019
Int. Cl. A61K 9/40 (2006.01); A61K 9/00 (2006.01); A61K 9/20 (2006.01); A61K 9/28 (2006.01); A61K 38/29 (2006.01); A61K 47/18 (2017.01); A61P 19/08 (2006.01); A61P 19/10 (2006.01)
CPC A61K 38/29 (2013.01) [A61K 9/0053 (2013.01); A61K 9/2013 (2013.01); A61K 9/2095 (2013.01); A61K 9/2806 (2013.01); A61K 47/18 (2013.01); A61P 19/08 (2018.01); A61P 19/10 (2018.01); A61K 9/0056 (2013.01)] 30 Claims
 
1. A pharmaceutical composition multi-unit dosage form comprising at least three discrete unit dosage forms bound to one another by a coating and/or matrix, each of said unit dosage forms comprising a therapeutically active agent and an absorption enhancer, said therapeutically active agent having a molecular weight in a range of 1 kDa to 100 kDa and/or being a BCS Class III agent, said unit dosage forms together comprising a therapeutically effective amount of said therapeutically active agent and an effective amount of said absorption enhancer, wherein said coating and/or matrix is formulated for immediate release of said unit dosage forms upon oral administration, such that the multi-unit dosage form disintegrates in gastric fluid and/or in saliva within no more than 5 minutes to thereby release said unit dosage forms, wherein said absorption enhancer is selected from the group consisting of NAC (8-N-(2-hydroxybenzoyl)aminocaprylate), NAD (10-N-(2-hydroxybenzoyl)aminodecanoic acid), 5-CNAC (8-N-(5-chlorosalicyloyl)aminocaprylic acid), 4-MOAC (8-N-(2-hydroxy-4-methoxybenzoyl)aminocaprylic acid), 4-CNAB (4-N-(2-hydroxy-4-chlorobenzoyl)aminobutanoic acid) and salts thereof, and wherein at least 50 weight percents of the unit dosage forms consists of said absorption enhancer.