Comparison of US Pharmacopeia Simulated Intestinal Fluid TS (without pancreatin) and Phosphate Standard Buffer pH 6.8, TS of the International Pharmacopoeia with Respect to Their Use in In Vitro Dissolution Testing

Abstract

Introduction Buffer solutions suitable for dissolution tests are described as such only in The United States Pharmacopeia (USP);The International Pharmacopoeia (IntPh),for example,broadly describes the composition of buffer solutions without specifying their fields of applicability. In this study Simulated Intestinal Fluid (SIFsp),which is described in The 26th United States Pharmacopeia (USP 26) as an 0.05 M buffer solution containing potassium dihydrogen phosphate (the pancreatin is omitted from the composition for most dissolution testing applications),and Phosphate Standard Buffer pH 6.8 TS, which is described in Volume 1 of The International Pharmacopoeia,Third Edition,(IntPh 3) as a mixture of 0.025 M potassium dihydrogen phosphate buffer solution and 0.025 M di-sodium hydrogen phosphate buffer solution,were investigated with respect to their interchangeability as dissolution test media. Both are pH 6.8 phosphate buffers,and they have similar osmolalities (114 mOsmol/kg) and buffer capacities (18 mEq/L/pH/unit). However, in the USP medium potassium (50mM) dominates over sodium (22mM) whereas in the IntPh buffer sodium (49.7mM) dominates over potassium (25mM). [Note: For the current investigations the IntPh phosphate buffer media was used as monographed in the 3rd edition,Volume 1. With the publication of Volume 5 the composition of the buffer pH 6.8 medium has been changed. Volume 5 describes a 0.04 M disodium hydrogen phosphate buffer solution for Buffer pH 6.8.]. The applicability and the interchangeability of these two compositionally similar but not identical buffers as dissolution media was investigated for products containing one of three drug substances: Metronidazole,a typical BCS Class 1 drug,and indometacin and ibuprofen,two drugs belonging to BCS Class 2. In each case several commercial products currently available on the German market were investigated. Products included uncoated,film coated,and sugar coated tablets as well as hard gelatin capsules.