In this study, Metrics Contract Services was tasked with a complex re-formulation project. Briefly, the free-acid form of an API, Compound XY, was previously manufactured as 5-mg, 10-mg, and 25-mg strength tablets using direct compression process. But the free-acid form of the compound proved to be poorly soluble in aqueous media. Hence, to increase the solubility of Compound XY, a salt form of the drug was explored.1 Out of all the salt forms investigated, potassium-salt was found to be the least sticky and least hygroscopic; therefore, it was selected for further study.

Metrics scientists were tasked with manufacturing the potassium-salt form tablets of Compound XY at all of the above strengths using the same tablet composition used to produce the free-acid form tablets. While manufacturing the potassium-salt form tablets, Metrics scientists observed various problematic issues described further. The blend flow from the hopper to die cavity was very poor, resulting in undesired weight variation. Additionally, the tablet surface showed discoloration, an effect that worsened with increasing tablet strength. As a result of the study presented here, the potassium-salt form of Compound XY was reformulated to yield tablets of acceptable dissolution, weight, properties, and appearance without adding any new excipients to the formulation.

BACKGROUND

The tablet weight of both the 5-mg and 10-mg formulations was 64 mg; the tablet weight of the 25-mg formulation was 160 mg. In order to expedite the reformulation development, it was decided to follow the same formulation process originally used to manufacture the free-form of Compound XY. Diverting from the previous formulation process would have affected the analytical methods.

During the manufacturing of 10-mg strength of Compound XY, scientists observed weight variation, so the tablet press was adjusted to accommodate the tablet weight. At this point, discoloration was observed on the tablet surface. Hence, the tablet press was disassembled, and the feed frame was inspected. It was discovered that the powder blend itself was discoloring as a part of the compression event. Additionally, the blend was sticking to the feed frame and the die table. Figure 1A shows the sticking of the blend to the die table and the scrapper.

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