WO2016038532A1 - Amorphous treprostinil diethanolamine - Google Patents
Amorphous treprostinil diethanolamine Download PDFInfo
- Publication number
- WO2016038532A1 WO2016038532A1 PCT/IB2015/056859 IB2015056859W WO2016038532A1 WO 2016038532 A1 WO2016038532 A1 WO 2016038532A1 IB 2015056859 W IB2015056859 W IB 2015056859W WO 2016038532 A1 WO2016038532 A1 WO 2016038532A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- treprostinil diethanolamine
- pharmaceutically acceptable
- solvent
- amorphous solid
- solid dispersion
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
Definitions
- the present disclosure relates to amorphous solid dispersion of treprostinil diethanolamine and its preparation thereof.
- Treprostinil diethanolamine is a prostacyclin vasodilator indicated for treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity.
- PAH pulmonary arterial hypertension
- ORENITRAM ® tablets contain treprostinil diethanolamine, a tricyclic benzindene analogue of prostacyclin and the chemical name is acetic acid, 2-[[(lR,2R,3aS,9aS)- 2,3,3a,4,9,9a-hexahydro-2-hydroxy-l-[(3S)-3-hydroxyoctyl]-lH-benz[f]inden-5-yl] oxy]-, complexed with 2,2'-iminobis[ethanol] (1: 1). Its structural formula is:
- Treprostinil diethanolamine is currently available as an active pharmaceutical ingredient in an extended-release formulation.
- Non-immediate release formulations such as controlled-release and extended-release formulations often utilize drug carriers to modify and/or improve the delivery of the drugs from the dosage form.
- Treprostinil diethanolamine is difficult to work with during formulation, thus limiting the pharmaceutical approaches that may be employed.
- the present invention addresses these shortcomings of the prior art by providing amorphous solid dispersion of treprostinil diethanolamine and one or more pharmaceutically acceptable carriers that can be readily processed into a final dosage form.
- the present invention provides amorphous solid dispersion of treprostinil diethanolamine and a process for the preparation thereof.
- Yet another aspect of the present invention is to provide a process for formulating different pharmaceutical compositions of amorphous solid dispersions of treprostinil diethanolamine.
- Figure 1 is an X-ray powder diffractogram of amorphous solid dispersion of treprostinil diethanolamine.
- the present invention provides amorphous solid dispersion of treprostinil diethanolamine and a process for the preparation thereof.
- One aspect of the present invention provides treprostinil diethanolamine in solid dispersion with one or more pharmaceutically acceptable carriers useful for the formulation of solid dosage forms.
- Another aspect of the present invention provides a process for the preparation of amorphous solid dispersion of treprostinil diethanolamine with pharmaceutically acceptable carriers, which may include the following steps: a) combining treprostinil diethanolamine with pharmaceutically acceptable carriers in a solvent;
- treprostinil diethanolamine and pharmaceutically acceptable carriers are dissolved in a suitable solvent or mixture of solvents.
- the treprostinil diethanolamine to be dissolved may be prepared by any prior-art process and may exist in crystalline or amorphous form.
- the treprostinil diethanolamine may be dissolved in the solvent while one or more pharmaceutically acceptable carriers may be dissolved or suspended in a solvent or mixture of solvents
- the solvent may be an alcoholic solvent, for example, methanol, ethanol, isopropanol, 1-butanol, 2-butanol, isoamyl alcohol, isobutyl alcohol, 1-pentanol, 1- propanol, 2-propanol, or mixtures thereof.
- the solvent may be hydrocarbon solvent, for example n-hexane, n-heptane, cyclohexane or mixture thereof.
- the solvent may be dimethyl formamide or dimethylsulfoxide.
- the pharmaceutically acceptable carriers may be soluble in the solvent. In other embodiments, the pharmaceutically acceptable carriers may be soluble or suspendable in the solvent.
- the specific pharmaceutically acceptable carriers that may be employed within the context of the present invention may be specified by the desired composition of the solid dispersion or the desired composition of the final pharmaceutical dosage form. Accordingly, the specific percentage of each pharmaceutically acceptable carrier may vary widely from about 0.1% to about 99.9%, depending on the particular composition desired. Examples of suitable pharmaceutically acceptable carriers include, as examples, povidone, silica gel, cellulose acetate, polyethylene glycol (for example, PEG-4000), and magnesium stearate.
- the amount of solvent and the temperature at which the solvent is held will vary based on the various components of the composition. Such parameters may be selected by one of ordinary skill in the art by routine experimentation.
- the solvent may then be removed. This may be carried out by methods well known in the art. For example, the solvent may be removed by distillation, evaporation, freeze drying, spray drying or agitated thin film drier. One of skill in the art will additionally recognize other methods by which solvent may be removed from the mixture. Next, amorphous solid dispersion of treprostinil diethanolamine with pharmaceutically acceptable carriers may be isolated.
- the solid dispersions of the present invention may be evaluated by performing a measurement of the X-ray powder diffraction pattern of the solid dispersion.
- the X-ray diffraction pattern of an exemplary solid dispersion of the disclosure was measured on a BRUKER D-8 Discover powder diffractometer equipped with goniometer of ⁇ /2 ⁇ configuration and Lynx Eye detector.
- the Cu-anode X-ray tube was operated at 40 kV and 30 mA. The experiments were conducted over the 2 ⁇ range of 2.0°-50.0°, 0.030° step size, and 0.4 seconds step time.
- a representative solid dispersion of treprostinil diethanolamine of the present invention with povidone, silica gel, cellulose acetate, polyethylene glycol (for example, PEG-4000), and magnesium stearate included as the pharmaceutically acceptable carriers has an x-ray powder diffraction pattern as shown in FIG. 1.
- reaction conditions e.g., reaction time or temperature
- amorphous solid dispersions of treprostinil diethanolamine of the present invention may be used in the formulation of tablets for oral administration.
- xylitol maltodextrin
- sodium lauryl sulfate magnesium stearate
- cellulose acetate triethyl citrate
- polyvinyl alcohol titanium dioxide
- polyethylene glycol polyethylene glycol
- talc a wide variety of pharmaceutically acceptable excipients that may be included in such a tablet formulation, including xylitol, maltodextrin, sodium lauryl sulfate, magnesium stearate, cellulose acetate, triethyl citrate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc.
- the tablets may also contain artificial flavorings and colorings.
- the tablets formulated using the amorphous solid dispersions of the present invention may have an extended-release profile.
- the extended-release profile may be accomplished by a variety of methods and formulations well known to those of skill in the art.
- amorphous solid dispersions of treprostinil diethanolamine disclosed herein may be included in formulations administered to patients for the treatment of pulmonary arterial hypertension to improve exercise capacity.
- An individual solid dosage form, such as tablets, may contain from about 0.125 mg treprostinil (or a pharmaceutically equivalent amount of a salt thereof) to about 2.5 mg treprostinil (or a pharmaceutically equivalent amount of a salt thereof).
- PEG-4000 (0.5 g) was added to a stirred solution of treprostinil diethanolamine (0.5 g) in methanol (5 mL). This solution was then stirred for 1 hour at room temperature. The reaction mixture was concentrated to dryness under vacuum at temperature below 40°C to obtain amorphous solid dispersion of treprostinil diethanolamine.
- Magnesium stearate (0.5 g) was added to a stirred solution of treprostinil diethanolamine (0.5 g) in methanol (5 mL). This solution was then stirred for 1 hour at room temperature. The reaction mixture was concentrated to dryness under vacuum at temperature below 40°C to obtain amorphous solid dispersion of treprostinil diethanolamine.
Landscapes
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present disclosure provides amorphous solid dispersion of treprostinil diethanolamine together with pharmaceutically acceptable carriers and a process for the preparation thereof. The amorphous solid dispersions of treprostinil diethanolamine disclosed herein are useful for the preparation of solid pharmaceutical dosage forms.
Description
AMORPHOUS TREPROSTINIL DIETHANOLAMINE
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of the earlier filing date of Indian Provisional Patent Application No. 4417/CHE/2014 filed on Sep 9, 2014.
BACKGROUND OF THE INVENTION
FIELD OF THE INVENTION
The present disclosure relates to amorphous solid dispersion of treprostinil diethanolamine and its preparation thereof.
BACKGROUND OF THE INVENTION
Treprostinil diethanolamine is a prostacyclin vasodilator indicated for treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity.
ORENITRAM® tablets contain treprostinil diethanolamine, a tricyclic benzindene analogue of prostacyclin and the chemical name is acetic acid, 2-[[(lR,2R,3aS,9aS)- 2,3,3a,4,9,9a-hexahydro-2-hydroxy-l-[(3S)-3-hydroxyoctyl]-lH-benz[f]inden-5-yl] oxy]-, complexed with 2,2'-iminobis[ethanol] (1: 1). Its structural formula is:
U.S. Patent No. 7,417,070 (which is hereby incorporated by reference) discloses treprostinil diethanolamine and crystalline Form A and crystalline Form B of treprostinil diethanolamine.
Treprostinil diethanolamine is currently available as an active pharmaceutical ingredient in an extended-release formulation. Non-immediate release formulations such as controlled-release and extended-release formulations often utilize drug carriers to modify and/or improve the delivery of the drugs from the dosage form. Treprostinil diethanolamine, however, is difficult to work with during formulation, thus limiting the pharmaceutical approaches that may be employed. The present invention addresses these shortcomings of the prior art by providing amorphous solid dispersion of treprostinil diethanolamine and one
or more pharmaceutically acceptable carriers that can be readily processed into a final dosage form.
SUMMARY OF THE INVENTION
The present invention provides amorphous solid dispersion of treprostinil diethanolamine and a process for the preparation thereof.
One embodiment of the present invention provides a process for the preparation of amorphous solid dispersion of treprostinil diethanolamine which may include the following steps:
a) combining treprostinil diethanolamine with one or more pharmaceutically acceptable carriers in a solvent;
b) removing the solvent; and
c) isolating amorphous solid dispersion of treprostinil diethanolamine.
Yet another aspect of the present invention is to provide a process for formulating different pharmaceutical compositions of amorphous solid dispersions of treprostinil diethanolamine.
BRIEF DESCRIPTION OF THE FIGURES
Further aspects of the present disclosure together with additional features contributing thereto and advantages accruing there from will be apparent from the following description of embodiments of the invention which are shown in the accompanying drawing figures wherein:
Figure 1 is an X-ray powder diffractogram of amorphous solid dispersion of treprostinil diethanolamine.
DETAILED DESCRIPTION OF THE INVENTION
It is to be understood that the figures and descriptions of the present invention have been simplified to illustrate elements that are relevant for a clear understanding of the invention, while eliminating, for purposes of clarity, other elements that may be well known. The detailed description will be provided herein below with reference to the attached drawings.
The present invention provides amorphous solid dispersion of treprostinil diethanolamine and a process for the preparation thereof. One aspect of the present invention provides treprostinil diethanolamine in solid dispersion with one or more pharmaceutically acceptable carriers useful for the formulation of solid dosage forms.
Another aspect of the present invention provides a process for the preparation of amorphous solid dispersion of treprostinil diethanolamine with pharmaceutically acceptable carriers, which may include the following steps: a) combining treprostinil diethanolamine with pharmaceutically acceptable carriers in a solvent;
b) removing the solvent; and
c) isolating amorphous solid dispersion of treprostinil diethanolamine.
According to some embodiments of the present invention, treprostinil diethanolamine and pharmaceutically acceptable carriers are dissolved in a suitable solvent or mixture of solvents. The treprostinil diethanolamine to be dissolved may be prepared by any prior-art process and may exist in crystalline or amorphous form.
In other embodiments of the present invention, the treprostinil diethanolamine may be dissolved in the solvent while one or more pharmaceutically acceptable carriers may be dissolved or suspended in a solvent or mixture of solvents
In some embodiments, the solvent may be an alcoholic solvent, for example, methanol, ethanol, isopropanol, 1-butanol, 2-butanol, isoamyl alcohol, isobutyl alcohol, 1-pentanol, 1- propanol, 2-propanol, or mixtures thereof. In other embodiment the solvent may be hydrocarbon solvent, for example n-hexane, n-heptane, cyclohexane or mixture thereof. In other embodiments, the solvent may be dimethyl formamide or dimethylsulfoxide. One of skill in the art will recognize numerous organic solvents capable of dissolving treprostinil diethanolamine.
Within the scope of the present invention, a wide variety of pharmaceutically acceptable carriers may be employed. In some embodiments, the pharmaceutically acceptable carriers may be soluble in the solvent. In other embodiments, the pharmaceutically acceptable carriers may be soluble or suspendable in the solvent. The specific pharmaceutically acceptable carriers that may be employed within the context of the
present invention may be specified by the desired composition of the solid dispersion or the desired composition of the final pharmaceutical dosage form. Accordingly, the specific percentage of each pharmaceutically acceptable carrier may vary widely from about 0.1% to about 99.9%, depending on the particular composition desired. Examples of suitable pharmaceutically acceptable carriers include, as examples, povidone, silica gel, cellulose acetate, polyethylene glycol (for example, PEG-4000), and magnesium stearate.
The amount of solvent and the temperature at which the solvent is held will vary based on the various components of the composition. Such parameters may be selected by one of ordinary skill in the art by routine experimentation. According to the present invention, the solvent may then be removed. This may be carried out by methods well known in the art. For example, the solvent may be removed by distillation, evaporation, freeze drying, spray drying or agitated thin film drier. One of skill in the art will additionally recognize other methods by which solvent may be removed from the mixture. Next, amorphous solid dispersion of treprostinil diethanolamine with pharmaceutically acceptable carriers may be isolated.
The solid dispersions of the present invention may be evaluated by performing a measurement of the X-ray powder diffraction pattern of the solid dispersion. The X-ray diffraction pattern of an exemplary solid dispersion of the disclosure was measured on a BRUKER D-8 Discover powder diffractometer equipped with goniometer of Θ/2Θ configuration and Lynx Eye detector. The Cu-anode X-ray tube was operated at 40 kV and 30 mA. The experiments were conducted over the 2Θ range of 2.0°-50.0°, 0.030° step size, and 0.4 seconds step time.
Within the context of the present invention, a representative solid dispersion of treprostinil diethanolamine of the present invention with povidone, silica gel, cellulose acetate, polyethylene glycol (for example, PEG-4000), and magnesium stearate included as the pharmaceutically acceptable carriers has an x-ray powder diffraction pattern as shown in FIG. 1.
With all of the reactions disclosed above, one of skill in the art will recognize that the reaction conditions (e.g., reaction time or temperature) may be adjusted to achieve appropriate yield without undertaking undue experimentation and without departing from the scope of the present disclosure.
Within the context of the present invention, the amorphous solid dispersions of treprostinil diethanolamine of the present invention may be used in the formulation of tablets for oral administration. One of skill in the art will recognize a wide variety of pharmaceutically acceptable excipients that may be included in such a tablet formulation, including xylitol, maltodextrin, sodium lauryl sulfate, magnesium stearate, cellulose acetate, triethyl citrate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc. The tablets may also contain artificial flavorings and colorings.
The tablets formulated using the amorphous solid dispersions of the present invention may have an extended-release profile. The extended-release profile may be accomplished by a variety of methods and formulations well known to those of skill in the art.
The amorphous solid dispersions of treprostinil diethanolamine disclosed herein may be included in formulations administered to patients for the treatment of pulmonary arterial hypertension to improve exercise capacity. An individual solid dosage form, such as tablets, may contain from about 0.125 mg treprostinil (or a pharmaceutically equivalent amount of a salt thereof) to about 2.5 mg treprostinil (or a pharmaceutically equivalent amount of a salt thereof).
Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the disclosure in any manner. Reasonable variations of the described procedures are intended to be within the scope of the present application. While particular aspects of the present application have been illustrated and described, it would be apparent to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the disclosure. It is therefore intended to encompass all such changes and modifications that are within the scope of this disclosure.
Example 1:
Povidone (2 g) and silica gel 230-400 mesh (2 g) were added to a stirred solution of treprostinil diethanolamine (2 g) in methanol (20 mL). This solution was then stirred for 1 hour at room temperature. The reaction mixture was concentrated to dryness under vacuum at temperature below 40°C to obtain amorphous solid dispersion of treprostinil diethanolamine.
Example 2:
Cellulose acetate (0.5 g) was added to a stirred solution of treprostinil diethanolamine (0.5 g) in methanol (5 mL). This solution was then stirred for 1 hour at room temperature. The reaction mixture was concentrated to dryness under vacuum at temperature below 40°C to obtain amorphous solid dispersion of treprostinil diethanolamine.
Example 3:
PEG-4000 (0.5 g) was added to a stirred solution of treprostinil diethanolamine (0.5 g) in methanol (5 mL). This solution was then stirred for 1 hour at room temperature. The reaction mixture was concentrated to dryness under vacuum at temperature below 40°C to obtain amorphous solid dispersion of treprostinil diethanolamine.
Example 4:
Magnesium stearate (0.5 g) was added to a stirred solution of treprostinil diethanolamine (0.5 g) in methanol (5 mL). This solution was then stirred for 1 hour at room temperature. The reaction mixture was concentrated to dryness under vacuum at temperature below 40°C to obtain amorphous solid dispersion of treprostinil diethanolamine.
Example 5:
Povidone K30 (35 g) was added to a stirred solution of treprostinil diethanolamine
(35 g) in methanol (175 mL). n-heptane (700 mL) and silica gel (230-400 mesh) (35 g) were added. The reaction mixture was stirred for 1 hour and then concentrated to dryness under vacuum at temperature below 40°C to obtain amorphous solid dispersion of treprostinil diethanolamine.
Claims
1. Amorphous solid dispersion of treprostinil diethanolamine with a pharmaceutically acceptable carrier.
2. The dispersion of claim 1, wherein the pharmaceutically acceptable carrier is selected from the group consisting of povidone, silica gel, cellulose acetate, polyethylene glycol, and magnesium stearate.
3. A process for preparing amorphous solid dispersion of treprostinil diethanolamine comprising:
a. combining treprostinil diethanolamine with pharmaceutically acceptable carriers in a solvent;
b. removing the solvent; and
c. isolating the amorphous solid dispersion of treprostinil diethanolamine.
4. The process of claim 3, wherein the solvent is selected from the group consisting of methanol, ethanol, isopropanol, 1-butanol, 2-butanol, isoamyl alcohol, isobutyl alcohol, 1-pentanol, 1-propanol, 2-propanol, n-hexane, n-heptane, cyclohexane and mixtures thereof.
5. The process of claim 3, wherein the pharmaceutically acceptable carrier is soluble or suspendable in the solvent.
The process of claim 3, wherein the pharmaceutically acceptable carrier is selected from the group consisting of povidone, silica gel, cellulose acetate, polyethylene glycol, and magnesium stearate.
7. The process of claim 3, wherein the isolating step is achieved by distillation, evaporation, freeze drying, spray drying, or agitated thin film drying.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN4417/CHE/2014 | 2014-09-09 | ||
| IN4417CH2014 | 2014-09-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2016038532A1 true WO2016038532A1 (en) | 2016-03-17 |
Family
ID=54249544
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2015/056859 WO2016038532A1 (en) | 2014-09-09 | 2015-09-08 | Amorphous treprostinil diethanolamine |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2016038532A1 (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018058124A1 (en) | 2016-09-26 | 2018-03-29 | United Therapeutics Corporation | Treprostinil prodrugs |
| CN111801313A (en) * | 2018-03-09 | 2020-10-20 | 奇诺因药物和化学工厂私人有限公司 | Process for preparing polymorph B of treprostinil diethanolamine salt |
| JP2021502384A (en) * | 2017-11-10 | 2021-01-28 | ディスパーソル テクノロジーズ リミテッド ライアビリティ カンパニー | Improved drug formulation |
| WO2021041320A1 (en) | 2019-08-23 | 2021-03-04 | United Therapeutics Corporation | Treprostinil prodrugs |
| EP3838884A1 (en) | 2019-12-19 | 2021-06-23 | Chirogate International Inc. | An efficient crystallization process for preparing ultrapure treprostinil and crystal prepared therefrom |
| WO2021211916A1 (en) | 2020-04-17 | 2021-10-21 | United Therapeutics Corporation | Treprostinil for use in the treatment of intersitial lung disease |
| WO2021252446A1 (en) | 2020-06-09 | 2021-12-16 | United Therapeutics Corporation | Fumaryl diketopiperidine prodrugs of treprostinil |
| WO2022132655A1 (en) | 2020-12-14 | 2022-06-23 | United Therapeutics Corporation | Methods of treating disease with treprostinil prodrugs |
| WO2022136545A1 (en) * | 2020-12-22 | 2022-06-30 | Radiometer Medical Aps | Blood sampler containing anti-platelet agent and water-soluble matrix material |
| WO2022187352A1 (en) | 2021-03-03 | 2022-09-09 | United Therapeutics Corporation | A dry powder composition of trestinil and its prodrug thereof and further comprising comprising (e)-3,6-bis[4-(n-carbonyl-2-propenyl)amidobutyl]-2,5-diketopiperazine (fdkp) |
| WO2023154705A1 (en) | 2022-02-08 | 2023-08-17 | United Therapeutics Corporation | Treprostinil iloprost combination therapy |
| WO2024155752A1 (en) | 2023-01-19 | 2024-07-25 | United Therapeutics Corporation | Treprostinil analogs |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070254032A1 (en) * | 2006-04-27 | 2007-11-01 | Argaw Kidane | Osmotic drug delivery system |
| US7417070B2 (en) | 2003-05-22 | 2008-08-26 | United Therapeutics Corporation | Compounds and methods for delivery of prostacyclin analogs |
| US8350079B2 (en) * | 2008-05-08 | 2013-01-08 | United Therapeutics Corporation | Treprostinil formulation |
-
2015
- 2015-09-08 WO PCT/IB2015/056859 patent/WO2016038532A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7417070B2 (en) | 2003-05-22 | 2008-08-26 | United Therapeutics Corporation | Compounds and methods for delivery of prostacyclin analogs |
| US20070254032A1 (en) * | 2006-04-27 | 2007-11-01 | Argaw Kidane | Osmotic drug delivery system |
| US8350079B2 (en) * | 2008-05-08 | 2013-01-08 | United Therapeutics Corporation | Treprostinil formulation |
Non-Patent Citations (2)
| Title |
|---|
| GHASTE R ET AL: "Solid dispersions: An overview", vol. 7, no. 5, 11 February 2009 (2009-02-11), pages 12pp, XP009137552, ISSN: 1918-5561, Retrieved from the Internet <URL:http://www.pharmainfo.net/reviews/solid-dispersions-overview> [retrieved on 20090211] * |
| SANDRIEN JANSSENS ET AL: "Review: physical chemistry of solid dispersions", JOURNAL OF PHARMACY AND PHARMACOLOGY, vol. 61, no. 12, 1 December 2009 (2009-12-01), pages 1571 - 1586, XP055023760, ISSN: 0022-3573, DOI: 10.1211/jpp/61.12.0001 * |
Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11672775B2 (en) | 2016-09-26 | 2023-06-13 | United Therapeutics Corporation | Treprostinil prodrugs |
| WO2018058124A1 (en) | 2016-09-26 | 2018-03-29 | United Therapeutics Corporation | Treprostinil prodrugs |
| JP7378393B2 (en) | 2017-11-10 | 2023-11-13 | オースティンピーエックス リミテッド ライアビリティ カンパニー | improved drug formulation |
| JP2021502384A (en) * | 2017-11-10 | 2021-01-28 | ディスパーソル テクノロジーズ リミテッド ライアビリティ カンパニー | Improved drug formulation |
| EP3706731A4 (en) * | 2017-11-10 | 2021-08-18 | Dispersol Technologies, LLC | Improved drug formulations |
| CN111801313A (en) * | 2018-03-09 | 2020-10-20 | 奇诺因药物和化学工厂私人有限公司 | Process for preparing polymorph B of treprostinil diethanolamine salt |
| JP7340534B2 (en) | 2018-03-09 | 2023-09-07 | キノイン・ジヨージセル・エーシユ・ベジエーセテイ・テルメーケク・ジヤーラ・ゼー・エル・テー | Process for producing polymorphic Form B of treprostinil diethanolamine salt |
| JP2021517138A (en) * | 2018-03-09 | 2021-07-15 | キノイン・ジヨージセル・エーシユ・ベジエーセテイ・テルメーケク・ジヤーラ・ゼー・エル・テー | Method for Producing Polymorph B of Treprostinyl Diethanolamine Salt |
| CN111801313B (en) * | 2018-03-09 | 2023-08-29 | 奇诺因药物和化学工厂私人有限公司 | Method for preparing polymorphic form B of treprostinil diethanolamine salt |
| WO2021041320A1 (en) | 2019-08-23 | 2021-03-04 | United Therapeutics Corporation | Treprostinil prodrugs |
| US11634443B2 (en) | 2019-08-23 | 2023-04-25 | United Therapeutics Corporation | Treprostinil prodrugs |
| EP3838884A1 (en) | 2019-12-19 | 2021-06-23 | Chirogate International Inc. | An efficient crystallization process for preparing ultrapure treprostinil and crystal prepared therefrom |
| US11826327B2 (en) | 2020-04-17 | 2023-11-28 | United Therapeutics Corporation | Treatment for interstitial lung disease |
| US20210330621A1 (en) | 2020-04-17 | 2021-10-28 | United Therapeutics Corporation | Treatment for interstitial lung disease |
| WO2021211916A1 (en) | 2020-04-17 | 2021-10-21 | United Therapeutics Corporation | Treprostinil for use in the treatment of intersitial lung disease |
| WO2021252446A1 (en) | 2020-06-09 | 2021-12-16 | United Therapeutics Corporation | Fumaryl diketopiperidine prodrugs of treprostinil |
| US11793780B2 (en) | 2020-06-09 | 2023-10-24 | United Therapeutics Corporation | Prodrugs of treprosiinil |
| WO2022132655A1 (en) | 2020-12-14 | 2022-06-23 | United Therapeutics Corporation | Methods of treating disease with treprostinil prodrugs |
| US11826328B2 (en) | 2020-12-14 | 2023-11-28 | United Therapeutics Corporation | Stable treprostinil prodrugs |
| WO2022136545A1 (en) * | 2020-12-22 | 2022-06-30 | Radiometer Medical Aps | Blood sampler containing anti-platelet agent and water-soluble matrix material |
| WO2022187352A1 (en) | 2021-03-03 | 2022-09-09 | United Therapeutics Corporation | A dry powder composition of trestinil and its prodrug thereof and further comprising comprising (e)-3,6-bis[4-(n-carbonyl-2-propenyl)amidobutyl]-2,5-diketopiperazine (fdkp) |
| WO2023154705A1 (en) | 2022-02-08 | 2023-08-17 | United Therapeutics Corporation | Treprostinil iloprost combination therapy |
| WO2024155752A1 (en) | 2023-01-19 | 2024-07-25 | United Therapeutics Corporation | Treprostinil analogs |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2016038532A1 (en) | Amorphous treprostinil diethanolamine | |
| ES2562843T3 (en) | Form IV of ivabradine hydrochloride | |
| WO2015176602A1 (en) | Tenofovir alafenamide complex, preparation method therefor and use thereof | |
| CN105646584B (en) | Tenofovir Chinese mugwort draws phenol amine fumarate crystal form and its preparation method and application | |
| WO2015139591A1 (en) | Crystalline form of dolutegravir sodium salt and preparation method therefor | |
| US20170129869A1 (en) | Amorphous form of eliglustat hemitartarate | |
| US20100297241A1 (en) | Amorphous Fesoterodine Fumarate | |
| WO2018073839A1 (en) | Amorphous osimertinib mesylate, processes for its preparation and solid amorphous dispersions thereof | |
| US10660963B2 (en) | Pharmaceutical composition containing tacrolimus and preparation methods thereof | |
| EP3102582A1 (en) | Crystalline forms of dolutegravir sodium | |
| JP2018502118A (en) | Process for preparing amorphous tenofovir arafenamide hemifumarate and its premix | |
| WO2016135755A1 (en) | Amorphous apremilast, premixes thereof, and novel crystalline forms of apremilast | |
| KR102276281B1 (en) | Pharmaceutically acceptable salts of pirlindole enantiomers for use in medicine | |
| JP2021523880A (en) | Solid form of dihydropyrimidine compound, its preparation method and its use | |
| US11466031B2 (en) | Polymorphic forms of bictegravir and its sodium salt | |
| WO2017163190A1 (en) | Amorphous ixazomib citrate and solid dispersion thereof | |
| JP5809367B2 (en) | Crystalline polymorph α of levonorgestrel and method for producing the same | |
| KR102697985B1 (en) | Pharmaceutical composition and method for preparing same | |
| WO2018078383A1 (en) | Pharmaceutical composition comprising amorphous selexipag | |
| US11872224B2 (en) | Amorphous solid dispersion formulation | |
| WO2021233434A1 (en) | New crystal form of bictegravir sodium and preparation method therefor | |
| CN111467344A (en) | Lacidipine solid dispersion and preparation method thereof | |
| TW201900646A (en) | Methanesulfonate polycrystal of type 5 phosphodiesterase inhibitor, preparation method and application thereof | |
| US20180030038A1 (en) | Polymorphic Forms of Afatinib Dimaleate | |
| WO2017130219A1 (en) | Amorphous solid dispersion of palbociclib |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 15774717 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 15774717 Country of ref document: EP Kind code of ref document: A1 |