Relations between crystallisation conditions and micromeritic properties of ibuprofen.
The effects of solvent, cooling rate and type of methacrylic polymer (Eudragit(R)) on the micromeritic properties (size, elongation ratio, roundness and fullness ratio), the temperature change in the crystallisation liquid, the crystal yield and the extent of agglomeration of ibuprofen crystals have been compared. Twenty batches of crystals were prepared and Latin square experimental design was applied with four levels for each factor. It was found that crystal yield (Y) is related to the extrapolated point of maximum rate of temperature-deviation (T(d)) with a logarithmic-type equation [Y=34.45lnT(d)-28.00] and to the area under the curve of temperature-deviation versus time (AUC) with a polynomial equation including cooling rate [Y=19.95AUC-1.57AUC/CR+63.00]. Crystal size is affected by the cooling rate and analysis of variance (ANOVA) showed that elongation ratio and fullness ratio of single crystals (P=0.05 and 0.05), as well as roundness and fullness ratio of agglomerates (P=0.05 and 0.1), are affected by the solvent. Post hoc statistical analysis of the solvent effects on the shape of crystals and agglomerates (Tukey's HSD multiple pairwise comparison test of means) indicated that their significance lies in the different polarity and may be attributed to interactions of solvent (acetone) with the growing crystal faces. Extent of crystal agglomeration was found to be inversely proportional to the ratio of elongation ratio/circle equivalent diameter of the single crystals.
Nikolakakis
I
I
Laboratory of Pharmaceutical Technology, School of Pharmacy, University of Thessaloniki, 54006, Thessaloniki, Greece. yannikos@pharm.auth.gr
Kachrimanis
K
K
Malamataris
S
S
D019540:Area Under Curve; D003460:Crystallization; D007052:Ibuprofen / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D013696:Temperature
D007052:Ibuprofen