Effect of a basic organic excipient on the dissolution of diclofenac salts.
Dissolution of diclofenac from compressed discs containing mixtures of a diclofenac salt and a basic excipient, in various w/w ratios, was examined. Two diclofenac salts, diclofenac deanol (DDNL) and diclofenac tert-butylamine, and the basic excipient 2-amino-2-methyl-1,3-propanediol (AMPD) were examined. Inclusion of the soluble basic excipient at high loadings enhanced the dissolution rate of diclofenac tert-butylamine fivefold; however, it retarded dissolution of the DDNL salt 40-fold in the weight fraction range 40-80% AMPD, despite the fact that AMPD is more than four times more soluble than DDNL. These findings were attributed to the solubilities of salts formed between diclofenac and the basic excipient used. The "salt conversion model" was developed to predict dissolution from mixtures of a salt of an ionizable drug and an ionizable excipient capable of forming a salt with the drug. Deviations from the model at high weight fractions of base and, in the case of the systems containing the more soluble drug, at low weight fractions of base were attributed to carrier-controlled dissolution. The present work illustrates that the solubility of potential salts, which may form between the drug and ionizable excipients present has an important influence on the dissolution of the drug from such compressed mixtures.
O'Connor
Karen M
KM
Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, Trinity College, Dublin, Ireland.
Corrigan
Owen I
OI
D018360:Crystallography, X-Ray; D004008:Diclofenac / Q000737:chemistry*; D004058:Diffusion; D007700:Kinetics; D015233:Models, Statistical; D011409:Propylene Glycols / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
D011409:Propylene Glycols; D004008:Diclofenac; C019250:2-amino-2-methyl-1,3-propandiol