公开(公告)号：US10973768B2

公开(公告)日：2021-04-13

申请号：US14381944

申请日：2013-02-28

Applicant: Bristol-Myers Squibb Company

Inventor： Deniz Erdemir ,  Shih-Ying Chang ,  Divyakant Desai ,  San Kiang

IPC: A61K9/48 ,  A61K9/28 ,  A61K9/16 ,  A61K9/14 ,  A61K31/155 ,  A61K9/24 ,  A61J3/10 ,  A61K9/20 ,  A61K31/7004 ,  A61K31/403

Abstract: The present disclosure relates to methods for making extended-release formulations of water-soluble active pharmaceutical ingredients such as metformin HCl. In one aspect, the disclosure provides a method that includes adding an aqueous solution of an active pharmaceutical ingredient to an agitated mixture of one or more release-modifying polymers and optionally one or more binders in one or more organic solvents, the one or more organic solvents together being an antisolvent for the active pharmaceutical ingredient, water being sufficiently soluble in the one or more organic solvents such that the water added as part of the aqueous solution dissolves in the mixture, the addition thereby precipitating the active pharmaceutical ingredient; separating the active pharmaceutical ingredient and the one or more release-modifying polymers and, if present, the one or more binders from the one or more organic solvents to yield co-processed particles; and drying the co-processed particles. The methods can be used to make dosage forms such as tablets having reduced amounts of release-modifying polymers.

公开(公告)号：US09248139B2

公开(公告)日：2016-02-02

申请号：US13716306

申请日：2012-12-17

Applicant: Bristol-Myers Squibb Company

Inventor： Shih-Ying Chang ,  Donald Kientzler ,  Deniz Erdemir ,  San Kiang ,  Tamar Rosenbaum

IPC: A61K31/675 ,  A61K9/14 ,  A61K9/20

CPC classification number: C07D471/04 ,  A61K9/14 ,  A61K9/146 ,  A61K9/2054 ,  A61K9/2095 ,  A61K31/675 ,  C07F9/6561

Abstract: A process for the production of a formulation of HIV attachment inhibitor piperazine tris salt prodrug compound involves dissolving the prodrug compound in a solvent to form a solution; adding a first quantity of a first anti-solvent to the solution; then dispersing a first quantity of HPMC in the solution; adding a second quantity of the first anti-solvent to the solution; dispersing a second quantity of HPMC in the solution; then adding a second anti-solvent to the solution so as to crystallize the compound with the HPMC and thereby form the formulation, wherein the second anti-solvent is a combination of acetone and isopropyl acetate (IPAC). The formulation is then washed, and dried.

Abstract translation: 制备HIV附着抑制剂哌嗪三盐前药化合物的制剂的方法包括将前药化合物溶解在溶剂中以形成溶液; 向溶液中加入第一量的第一种抗溶剂; 然后将第一量的HPMC分散在溶液中; 向溶液中加入第二量的第一种反溶剂; 将第二量的HPMC分散在溶液中; 然后向溶液中加入第二种抗溶剂，以使化合物与HPMC结晶，从而形成制剂，其中第二种抗溶剂是丙酮和乙酸异丙酯（IPAC）的组合。 然后将制剂洗涤并干燥。

公开(公告)号：US20150050335A1

公开(公告)日：2015-02-19

申请号：US14381944

申请日：2013-02-28

Applicant: Bristol-Myers Squibb Company

Inventor： Deniz Erdemir ,  Shih-Ying Chang ,  Divyakant Desai ,  San Kiang

IPC: A61K9/20 ,  A61K31/7004 ,  A61K31/403 ,  A61K9/48 ,  A61K9/28 ,  A61K9/16 ,  A61K9/14 ,  A61J3/10 ,  A61K31/155 ,  A61K9/24

CPC classification number: A61K9/2054 ,  A61J3/10 ,  A61K9/146 ,  A61K9/1682 ,  A61K9/1694 ,  A61K9/2086 ,  A61K9/209 ,  A61K9/2095 ,  A61K9/28 ,  A61K9/4833 ,  A61K9/4866 ,  A61K31/155 ,  A61K31/403 ,  A61K31/7004 ,  A61K2300/00

Abstract: The present disclosure relates to methods for making extended-release formulations of water-soluble active pharmaceutical ingredients such as metformin HCl. In one aspect, the disclosure provides a method that includes adding an aqueous solution of an active pharmaceutical ingredient to an agitated mixture of one or more release-modifying polymers and optionally one or more binders in one or more organic solvents, the one or more organic solvents together being an antisolvent for the active pharmaceutical ingredient, water being sufficiently soluble in the one or more organic solvents such that the water added as part of the aqueous solution dissolves in the mixture, the addition thereby precipitating the active pharmaceutical ingredient; separating the active pharmaceutical ingredient and the one or more release-modifying polymers and, if present, the one or more binders from the one or more organic solvents to yield co-processed particles; and drying the co-processed particles. The methods can be used to make dosage forms such as tablets having reduced amounts of release-modifying polymers.

Abstract translation: 本公开涉及制备水溶性活性药物成分例如二甲双胍HCl的缓释制剂的方法。 一方面，本公开提供了一种方法，其包括将活性药物成分的水溶液添加到一种或多种释放改性聚合物和任选的一种或多种有机溶剂中的一种或多种粘合剂的搅拌混合物中，所述一种或多种有机溶剂 溶剂一起是用于活性药物成分的抗溶剂，水在一种或多种有机溶剂中充分溶解，使得作为水溶液的一部分加入的水溶解在混合物中，从而沉淀活性药物成分; 从一种或多种有机溶剂中分离活性药物成分和一种或多种释放改性聚合物和（如果存在的话）一种或多种粘合剂以产生共加工颗粒; 并干燥共处理颗粒。 该方法可用于制备剂型，例如具有减少量的释放改性聚合物的片剂。

公开(公告)号：US20160102093A1

公开(公告)日：2016-04-14

申请号：US14974644

申请日：2015-12-18

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Shih-Ying Chang ,  Donald Kientzler ,  Deniz Erdemir ,  San Kiang ,  Tamar Rosenbaum

IPC: C07D471/04 ,  C07F9/6561

CPC classification number: C07D471/04 ,  A61K9/14 ,  A61K9/146 ,  A61K9/2054 ,  A61K9/2095 ,  A61K31/675 ,  C07F9/6561

Abstract: A process for the production of a formulation of HIV attachment inhibitor piperazine tris salt prodrug compound involves dissolving the prodrug compound in a solvent to form a solution; adding a first quantity of a first anti-solvent to the solution; then dispersing a first quantity of HPMC in the solution; adding a second quantity of the first anti-solvent to the solution; dispersing a second quantity of HPMC in the solution; then adding a second anti-solvent to the solution so as to crystallize the compound with the HPMC and thereby form the formulation, wherein the second anti-solvent is a combination of acetone and isopropyl acetate (IPAC). The formulation is then washed, and dried.

Abstract translation: 制备HIV附着抑制剂哌嗪三盐前药化合物的制剂的方法包括将前药化合物溶解在溶剂中以形成溶液; 向溶液中加入第一量的第一种抗溶剂; 然后将第一量的HPMC分散在溶液中; 向溶液中加入第二量的第一种反溶剂; 将第二量的HPMC分散在溶液中; 然后向溶液中加入第二种抗溶剂，以使化合物与HPMC结晶，从而形成制剂，其中第二种抗溶剂是丙酮和乙酸异丙酯（IPAC）的组合。 然后将制剂洗涤并干燥。

公开(公告)号：US20130164345A1

公开(公告)日：2013-06-27

申请号：US13716306

申请日：2012-12-17

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Shih-Ying Chang ,  Donald Kientzler ,  Deniz Erdemir ,  San Kiang ,  Tamar Rosenbaum

IPC: A61K31/675 ,  A61K9/14

CPC classification number: C07D471/04 ,  A61K9/14 ,  A61K9/146 ,  A61K9/2054 ,  A61K9/2095 ,  A61K31/675 ,  C07F9/6561

Abstract: A process for the production of a formulation of HIV attachment inhibitor piperazine tris salt prodrug compound involves dissolving the prodrug compound in a solvent to form a solution; adding a first quantity of a first anti-solvent to the solution; then dispersing a first quantity of HPMC in the solution; adding a second quantity of the first anti-solvent to the solution; dispersing a second quantity of HPMC in the solution; then adding a second anti-solvent to the solution so as to crystallize the compound with the HPMC and thereby form the formulation, wherein the second anti-solvent is a combination of acetone and isopropyl acetate (IPAC). The formulation is then washed, and dried.

Abstract translation: 制备HIV附着抑制剂哌嗪三盐前药化合物的制剂的方法包括将前药化合物溶解在溶剂中以形成溶液; 向溶液中加入第一量的第一种抗溶剂; 然后将第一量的HPMC分散在溶液中; 向溶液中加入第二量的第一种反溶剂; 将第二量的HPMC分散在溶液中; 然后向溶液中加入第二种抗溶剂，以使化合物与HPMC结晶，从而形成制剂，其中第二种抗溶剂是丙酮和乙酸异丙酯（IPAC）的组合。 然后将制剂洗涤并干燥。