Changes in crystallinity and solubility on comminution of digoxin and observations on spironolactone and oestradiol

Abstract

Using infrared spectroscopy, X-ray diffractometry, differential thermal analysis, scanning electron microscopy, solubility and dissolution rate measurements, it was demonstrated that the comminution of digoxin results in the appearance of an amorphous phase. The examination of spironolactone and 17 beta-oestradiol by infrared spectroscopy and differential thermal analysis showed that these compounds also undergo changes in their crystallinity on grinding. Since the dissolution characteristics of poorly soluble drugs may be complex functions of surface area and crystallinity, it is concluded that the most pertinent method for standardizing a sample of a polymorphic drug of low solubility is by means of a powder dissolution test, as the results embrace the influences of particle size, aggregation and polymorphism.

Particulate Analysis – Particle Size

“…A cyclone separation mechanism is used to collect the resultant micronized powder. To obtain small particles particularly those intended for inhalation, large quantities of energy are needed during micronization and this energy can affect the material being processed (Florence and Salole 1976;Otsuka and Kaneniwa 1990). Thus, micronized particles often have both a high surface energy and electrical charge (Buckton et al 1988).…”

Physicochemical Characterization of Pharmaceutical Solids

“…Crystals with smaller particle size resulted in compacts with higher tensile strength at a given pressure attributable to the larger number of contact points with the smaller sized particles. Dissolution rate is inversely proportional to the particle size, that is, the smaller the particle size of the API, the higher is the dissolution rate (Florence and Salole, 1976;Elamin et al, 1994).…”

Polymorphism: an evaluation of the potential risk to the quality of drug products from the Farmácia Popular Rede Própria

“…Studies revealed that for digoxin, the grinding process leads to amorphization (Florence et al, 1976). Storage of the amorphous form at room temperature results in a reduction in solubility (Chiou et al, 1979), which is a great concern considering that this antiarrhythmic has a narrow therapeutic window.…”