Solid state morphology screening of asiaticoside

Abstract

Solid state characterization of asiaticoside, major component in Centella asiatica extracts, was investigated. The solid state characterization includes solid phase characterization, solid state stability, solubility and incompatability with excipients. Solid phase screening was done by recrystallization of asiaticoside in various solvents. The morphology of crystals produced were needle-like (acicular) but different in their respective sizes. Solid state characterization of asiaticoside crystals by X-ray powder diffractometry (XRPD) found 2 polymorphs of asiaticoside. The first polymorph found in raw material asiaticoside and recrystallized product from methyl alcohol after underwent heating at 105°C for 3 hours and were designated as asiaticoside I. Recrystallized products from other solvents utilized are the second polymorph and was called asiaticoside II. Thermogravimetric analyses (TGA) of the 2 polymorphic forms were similar. The melting points were found to be approximately at 230°C. On the other hand the minor difference in endothermic peaks seen in differential scanning calorimetry (DSC) at 40-70°C implied that asiaticoside II may rearranged their internal structure and recrystallized to aasiaticoside I. Solubility of asiaticoside II was higher than asiaticoside I in the early stage but eventually decreased until stable and equal to the saturated concentration of asiaticoside I. This was due to the transformation of asiaticoside II to the-more-stable asiaticoside I during the solubility study. Solid state stability of asiaticoside was investigated using various temperatures and relative humidities. Solid state transformation of asiaticoside II to asiaticoside I was observed when the temperatures increased or the relative humidity decreased while asiaticoside I did not changed. The effect of temperature on chemical stability of asiaticoside I and asiaticoside II found to correlate well with increasing temperature. However, it was not possible to postulate the mechanism due to complex behavior which did not obey any simple kinetic equations tested. Various relative humidities also did not show any correlation with the decomposition of asiaticoside II. Humidity stability of asiaticoside I was proven to be the least stable at 62% RH. Moreover, incompatibility studies with selected excipients found that asiaticoside II degraded to a greater extent than asiaticoside I when mixed with talcum, magnesium stearate and silicon dioxide in the ratio of 1:1. However, degradation of the mixture of asiaticoside with spray dried lactose, pregelatinized starch and dibasic calcium phosphate in the ratio of 1:20 were very difficult to detect due to mixing homogeneity and sampling problems.