In vitro dissolution of proton-pump inhibitor products intended for paediatric and geriatric use in physiological bicarbonate buffer

Abstract

Proton-pump inhibitor (PPI) products based on enteric coated multiparticulates are design to meet the needs of patients who cannot swallow tablets such as children and older adults. Enteric coated PPI preparations exhibit delays in in vivo absorption and onset of antisecretory effects, which is not reflected by the rapid in vitro dissolution in compendial pH 6.8 phosphate buffer commonly used for assessment of these products. A more representative and physiological medium, pH 6.8 mHanks bicarbonate buffer, was used in this study to evaluate the in vitro dissolution of enteric coated multiparticulate-based PPI products. Commercially available omeprazole, lansoprazole and esomeprazole products were subject to dissolution tests using USP-II apparatus in pH 4.5 phosphate buffer saline for 45 min (acid stage) followed by pH 6.8 phosphate buffer or pH 6.8 mHanks bicarbonate buffer. In pH 6.8 phosphate buffer, all nine tested products displayed rapid and comparable dissolution profiles meeting the pharmacopeia requirements for delayed release preparations. In pH 6.8 mHanks buffer, drug release was delayed and failed the pharmacopeia requirements from most enteric coated preparations. Despite that the same enteric polymer, methacrylic acid-ethyl acrylate copolymer (1:1), was applied to all commercial multiparticulate-based products, marked differences were observed between dissolution profiles of these preparations. The use of pH 6.8 physiological bicarbonate (mHanks) buffer can serve as a useful tool to provide realistic and discriminative in vitro release assessment of enteric coated PPI preparations and to assist rational formulation development of these products.

Development and validation of dissolution testings in acidic media for rabeprazole sodium delayed-release capsules

“…In accord with previous experiments, there is a lag time for enteric-coated preparations to dissolve in the media of pH > 5.0 because of the slow dissolution of the enteric polymer and the dissolution of the drug through the dissolving polymer layer 5 , 39 . Although RAB is very soluble in water, results from this study show that a significant delay (approximately 30 min) in drug release from enteric-coated pellets of ACIPHEX ® Sprinkle in the medium of pH 6.0, which is agreed with the literatures reported previously 40–42 .…”

“…A predictive in vitro dissolution (or release) testing can serve as a useful tool during formulation development by providing discriminative in vitro data to guide the rational selection of desired formulation features 5 . A high-quality solid oral formulation should exhibit excellent effects in different physiological or pathological conditions of the human body after oral administration.…”

Use of bicarbonate buffer systems for dissolution characterization of enteric-coated proton pump inhibitor tablets

“…A compendial phosphate buffer (25 m m ), pH 6.8, was prepared by dissolving Na 2 HPO 4 and KH 2 PO 4 in distilled water according to the Japanese Pharmacopoeia (JP) 16th Edition . m Hanks buffer, pH 6.8, was composed of 136.9 m m NaCl, 5.37 m m KCl, 0.337 m m Na 2 HPO 4 , 0.441 m m KH 2 PO 4 , 0.812 m m MgSO 4 , 1.26 m m CaCl 2 and 4.17 m m NaHCO 3 as previously described . The pH of bicarbonate buffers (composed of 5, 15 and 25 m m NaHCO 3 ) and m Hanks buffer was adjusted and maintained by continuous sparging of CO 2 gas into the media before and during dissolution studies.…”

“…In fasting state, the fluids in the small intestine are mainly buffered by bicarbonate ions, which are secreted from the pancreas and intestinal epithelial cells . Therefore, bicarbonate buffers that simulate the ionic composition and buffering capacity of small intestinal fluids have been regarded as the more biorelevant buffer systems . Testing of some dosage forms containing ionizable drugs or excipients showed a larger variation of the dissolution profiles in bicarbonate buffers than in phosphate buffers .…”

“…Liu et al . also suggested that the use of m Hanks buffer can provide discriminative in vitro release testing for multiparticulate enteric‐coated proton pump inhibitor (PPI) products …”