Abstract: Aspects of the present application relates to crystalline form T5 of Tafamidis. The present application further relates to its pharmaceutical composition and preparative processes.
DESC:The following specification describes the invention.
INTRODUCTION
Aspects of the present application relate to solid forms of Tafamidis and preparative processes thereof. Specific aspects relate to crystalline form T5 of Tafamidis and processes for their preparation.
The drug compound having the adopted name “Tafamidis” has chemical name: 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid as below.
Tafamidis is a selective stabilizer of transthyretin developed by The Scripps Research Institute and marketed by Pfizer as VYNDAQEL® (Tafamidis meglumine) and VYNDAMAXTM (Tafamidis) oral capsule for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.
US 7214695 B2 patent first disclosed Tafamidis and its use thereof for the treatment of transthyretin amyloid disease. It further discloses a general procedure for the preparation of benzoxazoles, particularly Tafamidis. US 9249112 B2 patent discloses the meglumine salt of Tafamidis along with its amorphous and crystalline forms. The US 9770441 B2 patent discloses amorphous and crystalline forms (Form 1, 2, 4 and 6) of Tafamidis.
The reported solid forms of Tafamidis are not viable at industrial scale and there remains a need for alternate solid forms of Tafamidis and their preparative processes.
SUMMARY
In an aspect, the present application provides a crystalline Form T5 of Tafamidis, characterized by a PXRD pattern comprising the peaks at about 8.2, 11.6, 19.2 and 20.8° ± 0.2° 2?.
In another aspect, the present application provides a process for the preparation of crystalline Form T5 of Tafamidis, comprising the step of crystallizing Tafamidis from a mixture comprising water.
In another aspect, the present application provides a pharmaceutical composition comprising crystalline Form T5 of Tafamidis and atleast one pharmaceutically acceptable excipient.
BRIEF DESCRIPTION OF THE DRAWING
Figure 1 is an illustrative X-ray powder diffraction pattern of crystalline Form-T5 of Tafamidis, prepared by the method of Example 1.
DETAILED DESCRIPTION
Aspects of the present application relates to solid form of Tafamidis and the pharmaceutical compositions thereof. Specific aspect of present application relate to crystalline Form T5 of Tafamidis and their preparative processes.
In an aspect, the present application provides a crystalline Form T5 of Tafamidis, characterized by a PXRD pattern comprising the peaks at about 8.2, 11.6, 19.2 and 20.8° ± 0.2° 2?. In an embodiment, the crystalline Form-T5 is characterized by one or more additional peaks at about 13.0, 15.1, 20.2, 24.3, and 33.1° ± 0.2° 2?. In an embodiment, the present application provides crystalline Form-T5 of Tafamidis, characterized by a powder X-ray diffraction pattern, as illustrated by Figures 1.
In another aspect, the present application provides a process for the preparation of crystalline Form-T5 of Tafamidis, comprising the step of crystallizing Tafamidis from a mixture comprising water.
In embodiments, Tafamidis used in this aspect may be obtained by any methods known in the art or a reaction mixture comprising Tafamidis may be used directly.
In embodiments, the crystalline Form T5 may be isolated by separating the solids from the solvent through suitable techniques known in the art such as filtration, decantation and the like.
In embodiments, the isolated solid may be dried under suitable drying conditions such as aerial drying, drying under vacuum or inert gas at a suitable temperature of about 25°C or above.
In embodiments, the crystalline forms of Tafamidis of the present application are stable under thermal, humid and stress conditions. Further, the crystalline forms of present application exhibits superior solubility in solvents such as water, as compared to reported crystalline forms of Tafamidis.
In another aspect, the present application provides a crystalline Form T5 Tafamidis, and its the pharmaceutical compositions thereof, comprising Tafamidis with a chemical purity of atleast 99% by HPLC or atleast 99.5% by HPLC or atleast 99.9% by HPLC.
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 application in any manner. Variations of the described procedures, as will be apparent to those skilled in the art, are intended to be within the scope of the present application.
Definitions
The term "about" when used in the present application preceding a number and referring to it, is meant to designate any value which lies within the range of ±10%, preferably within a range of ±5%, more preferably within a range of ±2%, still more preferably within a range of ±1 % of its value. For example "about 10" should be construed as meaning within the range of 9 to 11 , preferably within the range of 9.5 to 10.5, more preferably within the range of 9.8 to 10.2, and still more preferably within the range of 9.9 to 10.1.
Examples
Example-1: Preparation of crystalline Form T5 of Tafamidis.
A mixture of Tafamidis (5g) was dissolved in DMSO (40mL) with concomitant heating at ~75oC. The mixture was cooled down to ~35oC followed by addition of water (20mL). The obtained solid was isolated and dried under vacuum to afford the title crystalline Form T5 of Tafamidis.
,CLAIMS:We Claim
Claim 1: A crystalline Form T5 of Tafamidis, characterized by a PXRD pattern comprising the peaks at about 8.2, 11.6, 19.2 and 20.8° ± 0.2° 2?.
Claim 2: A process for the preparation of crystalline Form T5 of Tafamidis of claim 1, comprising the step of crystallizing Tafamidis from a mixture comprising water.
Claim 3: A pharmaceutical composition comprising crystalline Form T5 of Tafamidis and at least one pharmaceutically acceptable excipient.
| # | Name | Date |
|---|---|---|
| 1 | 202041049413-STATEMENT OF UNDERTAKING (FORM 3) [12-11-2020(online)].pdf | 2020-11-12 |
| 2 | 202041049413-PROVISIONAL SPECIFICATION [12-11-2020(online)].pdf | 2020-11-12 |
| 3 | 202041049413-FORM 1 [12-11-2020(online)].pdf | 2020-11-12 |
| 4 | 202041049413-DRAWINGS [12-11-2020(online)].pdf | 2020-11-12 |
| 5 | 202041049413-ENDORSEMENT BY INVENTORS [03-11-2021(online)].pdf | 2021-11-03 |
| 6 | 202041049413-DRAWING [03-11-2021(online)].pdf | 2021-11-03 |
| 7 | 202041049413-CORRESPONDENCE-OTHERS [03-11-2021(online)].pdf | 2021-11-03 |
| 8 | 202041049413-COMPLETE SPECIFICATION [03-11-2021(online)].pdf | 2021-11-03 |