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MICRONIZED BOSENTAN AND PHARMACEUTICAL COMPOSITIONS THEREOF

IP.com Disclosure Number: IPCOM000234006D
Publication Date: 2014-Jan-07
Document File: 6 page(s) / 44K

Publishing Venue

The IP.com Prior Art Database

Abstract

The present disclosure relates to micronized particles of bosentan having a d90 value of about 2.0 µm to about 11.0 µm. It further relates to pharmaceutical compositions comprising said particles and processes for preparing such compositions.

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MICRONIZED BOSENTAN AND PHARMACEUTICAL COMPOSITIONS THEREOF

Abstract

The present disclosure relates to micronized particles of bosentan having a d90 value of about 2.0 µm to about 11.0 µm.  It further relates to pharmaceutical compositions comprising said particles and processes for preparing such compositions.

Reported herein are micronized particles of bosentan having a d90 value of about 2.0 µm to about 11.0 µm, in particular of about 4.0 µm to about 7.0 µm.

Reported herein are micronized particles having a d90 value of about 4.0 µm to about 7.0 µm; a d50 value of about 2.0 µm to about 3.0 µm; and a d10 value of about 0.1 µm to about 1.0 µm.

Reported herein is a process for the preparation of micronized particles of bosentan having a d90 value of about 2.0 µm to about 11.0 µm, using a dry milling technique.

Reported herein is a pharmaceutical composition comprising micronized particles of bosentan having a d90 value of about 2.0 µm to about 11.0 µm.  The pharmaceutical composition is a solid dosage form and comprises pharmaceutically acceptable excipients selected from the group comprising diluents, binders, disintegrants, lubricants, or mixtures thereof.

Also reported herein is a process for the preparation of the pharmaceutical composition, wherein the process comprises:

a)            mixing bosentan, a diluent, a disintegrant, and optionally a binder;

b)            optionally, granulating the blend of step a) by a dry granulation method or by using a solution or dispersion of a binder;

c)            optionally, mixing the granules of step b) with an extra-granular disintegrant;

d)           lubricating the blend of step a), step b), or step c) and compressing into tablets or filling into capsule shells.

The pharmaceutical composition prepared by using the process described herein is a tablet.  The tablets so disclosed may be further coated with a film coating.

“Bosentan”, as used herein, encompasses bosentan and its pharmaceutically acceptable salts, esters, ethers, isomers, hydrates, solvates, and polymorphs.  As bosentan is a poorly soluble drug belonging to BCS class II, reduction in particle size provides a viable option for improving solubility, and thereby the bioavailability of the drug.  Hence, it is necessary to obtain an optimum particle size for bosentan to improve its dissolution and bioavailability.

Particle size reduction may be carried out using various conventionally available mills such as a ball mill, attrition mill, vibratory mill, air jet mill, sand mill, or a bead mill.  The air jet mill can be used only for the dry milling process, whereas all the other mills may be used for both dry and wet milling.  The milling process may be carried out using bosentan alone, or with other pharmaceutically acceptable excipients.  During wet milling, water may be used as a medium for particle size reduction.  Particle size may be determined using known techniques like the use of light-scattering methods, e.g.,theMalvern® Mastersizer®.  Ram...