Pharmaceutical compositions with improved dissolution

Abstract

The invention relates to methods of screening mixtures containing a pharmaceutical compound and an excipient to identify properties of the pharmaceutical compound/excipient combination that retard solid-state nucleation. The invention further relates to increasing the solubility, dissolution and bioavailability of a drug with low solubility in gastric fluids conditions by combining the drug with a recrystallization/precipitation retardant and an optional enhancer.

Description

FIELD OF THE INVENTION The present invention relates to pharmaceutical compositions and methods for preparing same. BACKGROUND OF THE INVENTION Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide) is a substituted pyrazolylbenzenesulfonamide represented by the structure: Celecoxib belongs to the general class of non-steroidal anti-inflammatory drugs (NSAIDs). Unlike traditional NSAIDs, celecoxib is a selective inhibitor of cyclooxygenase II (COX-2) that causes fewer side effects when administered to a subject. The synthesis and use of celecoxib are further described in U.S. Pat. Nos. 5,466,823, 5,510,496, 5,563,165, 5,753,688, 5,760,068, 5,972,986, and 6,156,781, the contents of which are incorporated by reference in their entirety. Orally deliverable liquid formulations of celecoxib are discussed in U.S. Patent Application Publication No. 2002 / 0107250 in the name of Hariharan, et al., the contents of which are incorporated herein by reference...

AI Technical Summary

Benefits of technology

One advantage of the present invention is that the plurality of containers may be presented in a multiple well plate format or block and tube format such that at least 24, 48, 96, 384, or 1536 samples are assayed in parallel. Multiple block and tubes or multiwell plates may be assayed such that at least 1000, 3000, 5000, 7000, 10000, 20000, 30000, 40000, 50000, 60000, 70000, 80000, 90000, or 100000 samples are assayed. This is advantageous because the process may be operated in a semi-automated or automated way using existing multiple well plate format-based apparatus. At least the step of dispensing may be performed with automated liquid handling apparatus. Accordingly, it is possible to operate the process as a high throughput screen. Additionally, using a multiple well plate format, the scale of the screening is relatively low. For example, each sample may contain less than 100 mg, 50 mg, 25 mg, 10, mg, 5 mg, 750 ug, 500 ug, 250, ug, 100 ug, 75 ug, 50 ug, 25 ug, 10 ug, 1 ug, 750 ng, 500 ng, 250 ng, 100 ng, or less than 50 ng, depending on the api, sample size, etc. This therefore minimises the amount of active pharmaceutical ingredient material which is needed to identify excipients or properties of the combination of pharmaceutical compound and excipient that retard onset of nucleation. In this way, improved speed and relatively low cost are advantages.

The intimate mixture formed in the process may be achieved by any conventional method, including the use of a mixer during or after dispensing of the solutions. Once the mixture has been formed, it is generally advantageous to incubate the mixture at a constant temperature, such as approximately 37° C., to simulate in vivo conditions.

Measurement of onset of solid-state nucleation or precipitation may be determined by measuring light scattering of a mixture. This may be achieved by any conventional light scattering measurement, such as the use of a nephelometer. It is also possible to include a further step in which the crystallinity of the products of the solid-state nucleation or precipitation is determined. This step is conveniently pe

Problems solved by technology

Normally, the enhancer does not improve the length of time the api can remain supersatu

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