Dilution potential: a new perspective.

Abstract

The objective of this work was to develop a method to assess the dilution capacity of direct compression excipients based on a technique previously proposed by Minchom and Armstrong (MA). The technique involves the addition of increasing quantities of a poorly compactible (compressible) material to the excipient and measuring the resultant decrease in the AUC of the tensile strength versus compaction force profiles. The AUC of each mixture is divided by the AUC of the "0% mixture" to obtain MA's "work potential," called "area ratios" in the present study. The applicability of this approach was tested using three excipients differing in their deformation mechanisms: microcrystalline cellulose (Avicel PH 101, 102, 200, 301, 302) representing a plastic material; dibasic calcium phosphate (Cal-Star) representing a brittle material, and anhydrous lactose, which exhibits both brittle and plastic properties. Ascorbic acid or acetaminophen was the poorly compactible challenge material. In the first study, the MA method was found to apply only to Avicel PH 101, since the area ratios for mixtures containing different compositions of acetaminophen with either Cal-Star or anhydrous lactose remain constant until a certain percentage of drug is exceeded, after which a decline starts to be observed. Further work carried out on mixtures of different grades of Avicel with ascorbic acid revealed that MA's approach reflects only the ability of the excipient to handle internal stress induced by the drug and does not take into account the intrinsic ability of the drug-free excipient to form strong compacts. A new index was thus proposed, called the dilution capacity index (DCI), which weights the MA index by the AUC of the drug-free excipient. The results suggest that DCI can be used to compare different grades of microcrystalline cellulose and provide in-house quality control for microcrystalline cellulose suppliers.