Manufacturing Of Solid Dosage Forms Research Articles

Characterization of humidity-dependent changes in crystal properties of a new HMG-CoA reductase inhibitor in support of its dosage form development

Humidity-dependent changes in the crystal properties of the disodium salt of a new HMG-CoA reductase inhibitor (SQ-33600) were characterized using a combination of gravimetric, thermal, and spectral techniques. The drug substance was found to exhibit rapid moisture sorption and/or desorption, depending on the environmental conditions. Three crystalline solid hydrates and one liquid crystalline phase were identified, each having a definite stability over a range of humidity. The drug substance turned amorphous upon wet granulation, and the amorphous phase reconverted to crystalline hydrates upon exposure to 33–75% relative humidity. To avoid physical instability of dosage forms due to phase changes, manufacturing of solid dosage forms by dry processing below 52% relative humidity was recommended. The dissolution of drug from solid dosage forms was observed to be independent of the crystal form of the active.

Effect of Solvent-Deposition on Spironolactone Crystal Form

Spironolactone deposited from acetone and methanol onto glass particles in the forms obtained on recrystallisation, but adopted different forms on lactose due to the effects of solvent on the matrix.Solvent-deposition, the precipitation of solute onto a matrix surface by evaporation, is an established process in the manufacture of solid dosage forms, and is commonly used as a mixing technique. As reports of comprehensive studies on the effects of deposition systems on drug particle size, dissolution rate and stability had noted the occurrence of polymorphic behaviour1,2, it was considered of interest to examine whether forms with particular characteristics could be developed on solvent-dsposition. Spironolactone, a steroidal diuretic with variable and dissolution-dependent bioavailability3, was selected for study as it had been found to crystallise from volatile solvents in different forms exhibiting substantially different dissolution rates;4 powdered glass was employed as a model matrix.5This paper was presented in part at the 4th pharmaceutical Technology Conference, Edinburgh, April 1984.