Compaction behaviour and new predictive approach to the compressibility of binary mixtures of pharmaceutical excipients.
The compressibility of three pharmaceutical excipients (microcrystalline cellulose, lactose and anhydrous calcium phosphate) and their binary mixtures was studied. The aim of this work was to observe the impact of the mass composition of the mixture on the compressibility. The single-compound materials and their mixtures were compacted using instrumented presses. It allowed obtaining compression cycles (i.e., force-displacement curves) which were associated with energy measurements (specific compaction energy, Esp cp and specific expansion energy, Esp exp). It was observed that for the mixtures studied, the change of Esp cp with the mass composition could be fitted using a linear relationship (it was not the case with Esp exp). A linear relationship between the porosity of mixture's compacts and the mass composition was also obtained. Heckel's plots were then obtained for the three excipients and the mixtures. The mean yield pressure was calculated with the "in-die-method" and the "out-of-die method". A proportional relationship was not valid for the mean yield pressures. But, a predictive approach was proposed in order to obtain indirectly the mean yield pressure of a binary mixture if the data of the single materials were known. It used the linear mixing rule observed with the porosity. The validity was verified and compared with the experimental values. This comparison showed that it was possible to predict the mean yield pressure of binary mixtures from the accessible data of the single excipients.
Busignies
V
V
Centre d'études Pharmaceutiques de l'Université Paris XI, France.
Leclerc
B
B
Porion
P
P
Evesque
P
P
Couarraze
G
G
Tchoreloff
P
P
D002130:Calcium Phosphates / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding; D004355:Drug Stability; D007785:Lactose / Q000737:chemistry; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011208:Powders; D011312:Pressure; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D013718:Tensile Strength
D002130:Calcium Phosphates; D004364:Pharmaceutical Preparations; D011208:Powders; D013607:Tablets; D002482:Cellulose; C020243:calcium phosphate; D007785:Lactose; C109691:microcrystalline cellulose