US 2026/0248724 A1 · INJECTABLE HIGH CONCENTRATION PHARMACEUTICAL FORMULATIONS AND METHODS OF MANUFACTURING AND USE THEREOF

Abstract

The present invention provides compositions comprising one or more active pharmaceutical ingredients, wherein the compositions are in the form of high solids content concentrated suspensions capable of being injected in relatively low volumes into an animal using standard commercially available syringes. The invention also provides methods of making such compositions, particularly those compositions comprising high molecular weight active ingredients (e.g., antibodies, enzymes and other proteins and peptides) at relatively high therapeutic concentrations in the high solids content concentrated suspensions. The invention further provides methods of using such formulations in treating, preventing, and/or ameliorating certain diseases and physical disorders in animals, including humans, in need thereof.

Claims35

Dependent claims

A method of preparing a therapeutic composition comprising a concentrated suspension, said composition having a solids concentration of greater than about 350 mg/mL, wherein the concentrated suspension comprises one or more active pharmaceutical ingredients, one or more pharmaceutically acceptable excipients, at least one rheology modifier, and one or more non-solvent fluids, wherein said paste is capable of being injected subcutaneously, intracutaneously, intradermally, or intramuscularly into an animal in a volume of 3 mL or less at a flow rate of at least 30 μL/s using a commercially available needle/syringe combination, the method comprising (a) obtaining a spray-dried powder comprising said one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients;

(b) combining said powder with one or more diluents to form a suspension of said powder in said one or more diluents;
(c) mixing the suspension to evenly distribute the powder in the diluent;
(d) removing excess diluent from said suspension, thereby forming a paste;
and (e) mixing said paste to form an injectable high solids content paste.

1 more element

An apparatus for increasing the solids content of a suspension comprising a powder and a diluent, the apparatus comprising:

(a) a main body that is substantially hollow and defines an interior volume configured to receive and retain the suspension, the main body comprising at least two openings in fluid communication with the interior volume, wherein at least one of the openings is configured to be temporarily sealed;
(b) any number of auxiliary bodies, each auxiliary body being attachable to the main body or to another auxiliary body, wherein at least one auxiliary body is configured to provide a connection to a source of force or pressure for driving a separation process in which a portion of the diluent is removed from the suspension while the powder is substantially retained;
(c) any number of interchangeable bodies, each interchangeable body being attachable to the main body, to one or more auxiliary bodies or to one or more other interchangeable body, wherein at least one interchangeable body is configured to support one or more separation media;
and
(d) one or more separation medium disposed within the apparatus and configured to permit passage of the diluent therethrough while retaining substantially all of the powder, upon application of the force and/or pressure.

2 more elements

An apparatus for producing a viscoelastic suspension from a suspension comprising a powder and a diluent, the apparatus comprising:

(a) a main body that is substantially hollow and defines an interior volume for receiving the suspension, the main body comprising at least two openings in fluid communication with the interior volume;
(b) any number of auxiliary bodies attachable to the main body, wherein at least one auxiliary body provides a connection to a source of force or pressure configured to drive a separation process in which a portion of the diluent is removed from the suspension;
(c) any number interchangeable bodies attachable to the main body, wherein at least one interchangeable body supports one or more separation media configured to retain substantially all of the powder while permitting passage of the diluent;
(d) a pushing device disposed within or adjacent to the interior volume and configured to apply force to the suspension;
and
(e) one or more feedback systems operatively coupled to the apparatus, the feedback systems being configured to measure, observe, or otherwise determine one or more parameters indicative of the status of the separation process, and to use the one or more parameters to direct, adjust, monitor, or terminate the separation process, wherein the feedback system is electronic, mechanical, or any combination thereof.

3 more elements

A method of producing a viscoelastic suspension, the method comprising:

(a) introducing a suspension comprising one or more powders and one or more diluents into an interior volume of a main body of an apparatus, the main body being substantially hollow and comprising at least two openings in fluid communication with the interior volume;
(b) applying a force or pressure to the suspension within the interior volume via so as to cause a portion of the diluent to pass through one or more separation media supported by at least one interchangeable body attached to the main body, while retaining substantially all of the powder within the interior volume, thereby concentrating the powder relative to its concentration in the suspension prior to the application of the force or pressure;
and
(c) monitoring one or more parameters indicative of the status of the separation and/or the status of one or more parts of the apparatus using a feedback system;
and optionally
(d) determining a solids content of the composition following the application of the force or pressure;
and
(e) upon determining that the solids content exceeds a target solids content, diluting the composition with additional diluent and mixing the composition to substantially achieve the target solids content of the viscoelastic suspension, wherein the mixing is accomplished by manual mixing, low-shear mixing, planetary-centrifugal mixing, or by high-shear mixing if said suspension is determined to contain agglomerates;
or
(f) upon determining that the solids content is below a target solids content, reapplying force or pressure to the composition to remove additional diluent until the target solids content is substantially achieved.

7 more elements

Dependencies are inferred from the claim text.

Injectable high concentration pharmaceutical formulations and methods of manufacturing and use thereof

Life of this patent

Injectable high concentration pharmaceutical formulations and methods of manufacturing and use thereof

Life of this patent

Abstract

Claims35