Formulation of Sustained-Release Ketorolac Tromethamine Pellets - Pharmaceutical Technology

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Formulation of Sustained-Release Ketorolac Tromethamine Pellets
The authors evaluated the effect of polymer composition on the drug-release profile and the effect of storage conditions on dissolution characteristics.

Pharmaceutical Technology
Volume 32, Issue 12, pp. 58-61

Table I: Composition of the various coating formulations, each containing 5% of ketorolac tromethamine.
Subsequently, the prepared KT pellets were sieved (2 mm) and coated by four coating formulations using various proportions of Eudragit RL and Eudragit RS (see Table I).

Evaluation of KT pellets. The flowability of the nonpareil coated seeds was evaluated using the angle of repose method (14). To determine the KT content in the pellets, an accurately weighed amount of pellets containing 10 mg KT was sonicated with 100 mL of methanol for 30 min. The dispersion was then filtered, 5 mL of the filtrate was diluted with 50 mL methanol, and KT content was determined using UV spectrophotometry at 323 nm.

Determination of KT for stability study. In accordance with US Pharmacopeia 26 (15), the mobile phase was a degassed mixture of methanol, water, and glacial acetic acid (55:44:1), with a flow rate of 1.2 mL/min. The high-performance liquid chromatography (HPLC) system (C-R7A pluschromatopac, Shimadzu, Kyoto, Japan) was fitted with a column (250 X 4.6 mm, 5-μm particle size) and a 254-nm detector.

In vitro release (dissolution test). Drug release from prepared pellets was assessed using the USP 26 dissolution apparatus, Type I. Appoximately 337 mg of coated pellets were placed in 750 mL of phosphate buffer pH 6.8 as the dissolution medium. The temperature was maintained at 37 0.5 C and agitated at a rate of 90 rpm. At time intervals 1, 2, 3, 4, 5, 6, 7, 8, and 12 h, samples were withdrawn, filtered, suitably diluted, and the drug concentration was determined with spectrophotometry at 323 nm.

Release kinetic study. The release of KT was fitted to different release models to identify the mechanism of release kinetics from the prepared pellets.

Stability study. The prepared pellets were stored at various conditions; namely, 40 C and 75% RH; and 30 C and 75% RH for 4 months; and at shelf conditions (25 C and 60% RH) for 7 months.

Results and discussion

Figure 1: Dissolution-rate profiles of ketorolac tromethamine sustained-released formulations (formulations I–IV). (ALL FIGURES ARE COURTESY OF THE AUTHORS.)
The effect of the polymer composition used in coating the drug-loaded beads; namely Eudragit RL:Eudragit RS (1:2 and 1:3, respectively) on KT dissolution is shown in Figure 1. Generally, the observed drug release from the coated beads can be arranged according to the following increasing order: Eudragit RS < Eudragit RL:Eudragit RS, 1:3 < Eudragit RL:Eudragit RS, 1:2 < Eudragit RL. The authors observed a reduction of release from 88% in pellets coated with Eudragit RL to only 50% release in pellets coated with Eudragit RS after 2 h of dissolution. Corresponding values were 58.9% and 66.3% for pellets coated with a blend of Eudragit RL:Eudragit RS (1:3 and 1:2, respectively) (see Figure 1).


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