API in Capsule Services Save Clients Time, Money

Case Study 1:  API in Capsule Services Save Clients Time, Money

A pharmaceutical manufacturer had a problem: It needed to reduce the amount of fill in its 1-milligram-dose encapsulated product by 50 and 75 percent while adhering to a tight schedule and budget. The existing product was a dry blend filled into a hard gelatin capsule that had already been validated for assay, uniformity, and stability. But time constraints prevented the company from developing lower-potency blends that could be encapsulated volumetrically. And filling the capsules gravimetrically by hand would be too labor-intensive and time-consuming.

In search of a solution, the company brought its problem to Xcelience, a formulation development company based in Tampa, FL. Xcelience suggested using its Xcelodose 600, micro-filling system supplied by Capsugel, Greenswood, SC. The system typically fills neat API into capsules for use in clinical trials. In fact, Xcelience had validated the system for GMP manufacturing in early 2005 and had since used it to fill numerous APIs into capsules at weights of 100 micrograms to 500 milligrams. In this case, Xcelience suggested using the micro-filling method for the manufacturer’s lower-dose products, even though they were powder blends, not neat APIs.

The main concern was blend segregation during filling since the micro-filling system triggers powder flow by tapping on its dosing head. Therefore, Xcelience first needed to demonstrate that the technique would provide content uniformity that was the same as or better than that provided by conventional capsule filling.

In practice, the micro-filling system dispensed 30 and 60 milligrams of the blend (1 percent API and 99 percent pre-gelatinized starch) into size 3 hard gelatin capsules. Then, workers recorded the weight of each filled capsule. HPLC analysis was used to determine content uniformity.

Statistical analysis showed that the content determined by weight and assay of both product batches was not significantly different from the existing product. The 230 capsules filled with 30 milligrams had a mean of 98.9 percent of the target weight, with a relative standard deviation (RSD) of 2.2 percent. In a 30-capsule assay, the mean was 100 percent of the label claim, with an RSD of 1.9 percent. The 231 capsules filled with 60 milligrams had a mean of 99.4 percent of the target weight, with an RSD of 0.9 percent. In a 30-capsule assay of the 60 milligram capsules, the means was 99.6 percent of the label claim, with an RSD of 1.8 percent. These results confirmed that the micro-filling system could uniformly fill the capsules with the blend without segregation.

With Xcelience’s help, the pharmaceutical manufacturer achieved its goal on time and within its budget and did not spend any time or money on product or process development.

As seen in the March 2007 issue of Tablets & Capsules. Available at www.tabletscapsules.com.