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 with the same percentage of Aquacoat coating, it was concluded that in vitro dissolution of oral controlled-release formulations should be performed in both gastric and intestinal media for ionizable drugs. Ketoprofen (weak acid, pKa 4.8), nicardipine HCl (salt of weak organic base, pKa 8.6), and acetaminophen (very weak organic acid, pKa 9.7, not ionized at physiologic pH) provided different dissolution characteristics in enzyme-free simulated 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 related to drug ionization even though the solubility of the coating (ethylcellulose) 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 at approximately the same rate in both acidic and basic media. A comparison of drug release profiles for nicardipine HCl nude beads was also investigated 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, Van-Kel Industries, 5 and 10 dpm). Release profiles obtained from all methods were similar, indicating that the three dissolution methods were comparable.
Sorasuchart
W
W
College of Pharmacy, Oregon State University, Corvallis 97331, USA.
Wardrop
J
J
Ayres
J W
JW
D000082:Acetaminophen / Q000737:chemistry; D018712:Analgesics, Non-Narcotic / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D002121:Calcium Channel Blockers / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007660:Ketoprofen / Q000737:chemistry; D007700:Kinetics; D009529:Nicardipine / Q000737:chemistry; D013608:Tablets, Enteric-Coated
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D005079:Excipients; D013608:Tablets, Enteric-Coated; D000082:Acetaminophen; D007660:Ketoprofen; D009529:Nicardipine