Drug release from spray layered and coated drug-containing beads: Effects of pH and comparison of different dissolution methods

Based on dissolution profiles of three model drugs on spray layered beads w ith the same percentage of Aquacoat(R) coating, it was concluded that in vi tro dissolution of oral controlled-release formulations should be performed in both gastric and intestinal media for ionizable drugs. Ketoprofen tweak acid, pK(a) 4.8), nicardipine HCl (salt of weak organic base, pK(a) 8.6), and acetaminophen (very weak organic acid, pK(a) 9.7 not ionized at physiol ogic pH) provided different dissolution characteristics in enzyme-free simu lated gastric fluid (pH 1.4) and enzyme-free simulated intestinal fluid (pH 7.4), indicating that the rate of drug release was pH dependent and relate d to drug ionization even though the solubility of the coating (ethylcellul ose) is pH independent. In acidic media, ketoprofen release from the beads containing low-level coating (3%) was slower than that of nicardipine HCl, with the opposite holding true in basic media. Acetaminophen was released a t approximately the same rate in both acidic and basic media. A comparison of drug release profiles for nicardipine HCl nude beads was also investigat ed among three different dissolution methods: USP dissolution apparatus I ( basket method, 50 rpm), USP dissolution apparatus II (paddle method, 50 rpm ), and USP dissolution apparatus III (Bio-Dis(R), Van-Kel Industries, 5 and 10 dpm). Release profiles obtained from all methods were similar, indicati ng that the three dissolution methods were comparable.