Drug-excipient interactions resulting from powder mixing. III: Solid state properties and their effect on drug dissolution

• Published in: Journal of pharmaceutical sciences Vol. 75; no. 6; p. 534
• Main Authors: Chowhan, Z T, Chi, L H
• Format: Journal Article
• Language: English
• Published: United States 01.06.1986
• Subjects: Capsules; Chemistry, Pharmaceutical; Excipients; Kinetics; Microscopy, Electron, Scanning; Particle Size; Pharmaceutical Preparations - analysis; Powders; Prednisone - analysis; Solubility; Starch
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600750603

Micronized prednisone was used to study the effect of powder mixing on drug-excipient interactions and their effect on in vitro dissolution from uncompacted, hand-filled capsules. Two powder formulations contained CaHPO4 X 2H2O (dibasic calcium phosphate dihydrate) as a filler and potato starch or sodium starch glycolate as a disintegrant. The third powder formulation contained pregelatinized starch as a disintegrant/filler. The lubricant in these formulations was magnesium stearate. When drug, CaHPO4 X 2H2O, and the disintegrant were thoroughly mixed and hand filled into capsules without compaction, only approximately 70% of the drug dissolved in 30 min. The incomplete dissolution of the drug was caused by the formation of agglomerates and the inclusion of the drug particles by these agglomerates. In contrast, when a mixture of drug and pregelatinized starch was used, complete dissolution of the drug was achieved after 30 min due to the absence of agglomeration and inclusion. Prolonged mixing of the formulation containing CaHPO4 X 2H2O with magnesium stearate resulted in a decrease in the dissolution rate. The total amount of the drug dissolved at the end of 30 min was reduced from 70 to 20%. The decrease in the rate of drug dissolution resulted from drug-excipient interactions which caused flaking of the magnesium stearate particles. The adhesion of these flakes to the drug particles and drug-excipient agglomerates resulted in hydrophobic coating which reduced water penetration. The rate of drug dissolution was not affected when drug and pregelatinized starch were mixed with magnesium stearate for a prolonged time due to the absence of magnesium stearate flaking and film formation.