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Abstract:  The purpose of this study was to determine the pharmaceutical acceptability and chemical stability of naratriptan hydrochloride in three extemporaneously compounded suspension formulations.

The naratriptan-hydrochloride oral suspensions were prepared from 2.5-mg commercial tablets yielding a nominal naratriptan concentration of 0.5 mg/mL. The suspension vehicles selected for testing were Syrpalta,® an equal-parts mixture of Ora-Plus™ and Ora-Sweet,™ and an equal-parts mixture of Ora-Plus and Ora-Sweet SF.™ The tablets were crushed and thoroughly triturated to a fine powder using a porcelain mortar and pestle. The powder was incorporated into a portion of the Syrpalta or Ora-Plus suspension vehicle and mixed until homogeneous. The mixtures were then brought to volume with Syrpalta, Ora-Sweet or Ora-Sweet SF, as appropriate. The suspensions were packaged in amber, plastic, screw-cap prescription bottles and stored at 23°C for seven days and 4°C for 90 days.

An adequate suspension was never achieved in Syrpalta. The crushed-tablet powder did not produce a uniformly dispersed mixture and exhibited clumping and a high rate of sedimentation. A distinct layer of the solid tablet material settled immediately after shaking. Over the next four hours, a densely packed, yellow, caked layer formed at the bottom of the containers, making resuspension difficult. During storage, the caking became worse. Chemical analysis was not performed.

The Ora-Plus and Ora-Sweet or Ora-Sweet SF suspensions had a slight greenish cast and were resuspended without difficulty by shaking for approximately ten seconds, yielding easily poured and homogeneous mixtures throughout the study. Visible settling and layering did not begin for four hours with the Ora-Sweet suspension and 24 hours for the Ora-Sweet SF suspension. High-pressure liquid chromatographic analysis found that the naratriptan concentration in both suspensionvehicle combinations exhibited little or no loss for seven days at 23°C and 90 days at 4°C. At least 96% of the initial concentration remained at all time points.

Naratriptan hydrochloride extemporaneously prepared as oral suspensions from tablets in equal-parts mixtures of Ora- Plus suspension vehicle with Ora-Sweet and with Ora-Sweet SF syrups was pharmaceutically acceptable and chemically stable for at least seven days at 23°C and 90 days at 4°C. Syrpalta was unacceptable for use as a vehicle for naratriptan hydrochloride suspensions prepared from tablets.

Related Keywords: chemical stability, high-pressure liquid chromatography, naratriptan, oral suspension, Syrpalta, tablets

Related Categories: PEER-REVIEWED, STABILITIES, COMPATIBILITIES

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