Metrics AAPS Poster Presentation Examines Filler Moisture Absorption

Long-term storage comparative analysis between two common fillers finds mannitol protects better

Greenville, NC, November 19, 2010 --( When pharmaceutical scientists need a low-moisture-grade inert filler for drug formulations, they often turn to mannitol or Avicel,® two excipients that inhibit a tablet’s ability to absorb moisture over time. But which filler works better in the long run?

A team at Metrics Inc. led by Anshul Gupte, PhD, development scientist, conducted research to help answer that question. Gupte presented the team’s findings Nov. 17 at a poster session at the American Association of Pharmaceutical Scientists annual conference.

The team started by creating three combinations of Avicel and mannitol – the first consisted of 100 percent Avicel, the second consisted of 75 percent Avicel/25 percent mannitol, and the third consisted of 25 percent Avicel/75 percent mannitol. Where mannitol was used, it was as intra-granular filler. Because it minimizes moisture addition, a roller compaction method was employed as granulation technique.

The tablets were stored long term under two stability conditions: At 25 degrees Celsius and 60-percent relative humidity, and at 40 degrees Celsius and 75-percent relative humidity in calibrated and under ICH storage conditions stability chambers.

The team analyzed the tablets initially and again after three and seven months of storage for assay and impurity levels, moisture and dissolution. Any thermal changes in the drug were tracked with differential scanning calorimetry initially and after three and seven months of stability storage.

Metrics scientists determined that as filler, mannitol better protected against degradation during long-term stability storage.

“We actually anticipated this result because we know that Avicel absorbs moisture over time,” Gupte said. “But it’s still very practical research. Regardless of the compound, Metrics can demonstrate to clients that we have data backing up our recommendations. When you’re a client, this kind of research offers peace of mind and gives you even more confidence in your contract partner.”

Metrics Inc. is one of the most respected contract pharmaceutical development and manufacturing companies in the United States today. Started as an analytical laboratory in 1994, Metrics has evolved into a full-service provider of quality pharmaceutical formulation development; first-time-in-man (FTIM) formulations; clinical material manufacturing (CTM) for Phase I, II and III trials; commercial manufacturing; and analytical method development and validation services.

Metrics has particular expertise in FTIM and Phase I, II, and III CTM manufacturing, having conducted more than 120 FTIM projects for different chemical entities in the last five years alone – while developing more than 700 batches of CTM in the same period.

Metrics, Inc.
Karen Stinneford