(536a) Using Powder Surface Energies to Predict Mixing Properties of Model Excipient-API Blends

During pharmaceutical processing it is common to mix dry blends of different components. During transport or dispensing of this blend, the components may segregate. This can be particularly troublesome when the API is not dispensing uniformly. This can lead to dosage irregularities during production. Therefore, predicting blend stability of different mixtures can be valuable in optimizing product processing and formulation.

METHODS:

Binary blends of acetaminophen with the excipients were tested for initial goodness-of-blend (% RSD and drug loading) as well as blend stability after applied mechanical energy. Acetaminophen and excipients were sieved such that the largest acetaminophen particles were smaller than the smallest excipient particles. The blends were placed above a screen sized such that acetaminophen could pass through and tapped in order to promote drug loss if blends were not cohesive. Inverse Gas Chromatography (IGC) was used to measure the surface energy values of the Acetaminophen and excipients, independently. Then, the spreading coefficient was used to predict blend behavior.

RESULTS AND DISCUSSION:

The acetaminophen-mannitol formed a good initial blend and showed no loss upon tapping. Acetaminophen-microcrystalline cellulose formed a good initial blend, but showed significant loss of drug upon tapping. Acetaminophen-Prosolv showed a poor initial blend, but no significant loss upon tapping. The spreading coefficients (Acetaminophen over excipient) correlated well with the mechanical data. The spreading coefficients were as follows: 23.7, 18.2, and 8.6 mJ/m² for the Acetaminophen/mannitol, Acetaminophen/microcrystalline cellulose, and Acetaminophen/Prosolv mixtures, respectively. Higher spreading coefficients indicate the Acetaminophen is more likely to stick to the larger excipient particles.

CONCLUSIONS:

Both mechanical (% RSD and blend stability) and thermodynamic (spreading coefficient) mixing parameters indicated the following trend of excipients when blended with Acetaminophen: mannitol > microcrystalline cellulose > Prosolv. Therefore spreading coefficients obtained through the individual components' surface energy values could be used to predict ultimate blend performance.