The effect of particle size reduction on digoxin crystal properties

Quantitative Crystallinity Determinations for β-Lactam Antibiotics by Solution Calorimetry: Correlations with Stability

“…The more exothermic heat of solution for mortar-ground cephalothin sodium (Sample 21, Table I) was consistent with the observed loss of crystallinity on grinding (6,10,14). A quantitative comparison of X-ray and calorimetric crystallinities is given in Table I1 for a series of cephalothin sodium samples.…”

“…Surface tension was measured with a Wilhelmy platinum plate attached to an ele~trobalance~ whose output was fed into a dual-pen recorder8. The methods for the measurement of the surface tension of aqueous solutions and of the change of the surface pressure of the phospholipid monolayer as a function of time after the injection of the drug in the subphase already were described (6)(7)(8). The criterion of equilibrium was the constancy, f 0.1 dyne/cm, of the surface pressure increment, AT, over 30 min.…”

“…Partial crystallinity is a special class of polymorphism and may have significant effects on dissolution rates (5,6) and chemical stability (7). The magnitude of the observed difference in the dissolution rate (5,6) or stability (7) between amorphous and crystalline phases suggests that even a small amount of amorphous phase in an otherwise crystalline sample is sufficient to alter measurably physical and chemical properties.…”

The influence of digoxin particle size on absorption of digoxin and the effect of propantheline and metoclopramide.

“…Shaw & Carless (1974) showed in patients that when administered within a rice paper cachet, absorption was more rapid and complete with digoxin particles of 12 and 3.7 gm size than with particles of 22 tLm, and that 7 days treatment with the 3.7 gm material produced significantly higher steady state plasma digoxin levels than with 22 gm particles. Florence, Salole & Stenlake (1974) reported increased dissolution rate of digoxin after milling to reduce particle size. Shah, Pytelewski, Eisen & Jarowski (1974) confirmed that milling of digoxin enhanced its dissolution rate and also demonstrated significantly increased peak blood levels of digoxin in rats following oral administration of digoxin milled with lactose as compared to unmilled digoxin and lactose.…”

Estimation of the degree of crystallinity in digoxin by X-ray and infrared methods

“…Studies by Florence, Salole & Stenlake (1974) and Florence & Salole (1975) showed that ball milling may lead to a transformation of digoxin from the crystalline to the amorphous state, with a consequent increase in the dissolution rate and the apparent solubility. Other workers (Jounella & Sothmann, 1973;Shaw, Carless & others, 1973) demonstrated that the bioavailability of digoxin depends upon particle size and solubility and/or dissolution rate of the drug administered.…”