TY - JOUR
T1 - Evolution of a physiological pH 6.8 bicarbonate buffer system
T2 - application to the dissolution testing of enteric coated products
AU - Liu, F.
AU - Merchant, H.A.
AU - Kulkarni, R.P.
AU - Alkademi, M.
AU - Basit, A.W.
N1 - Original article can be found at : http://www.sciencedirect.com Copyright Elsevier
PY - 2011/5
Y1 - 2011/5
N2 - The use of compendial pH 6.8 phosphate buffer to assess dissolution of enteric coated products gives rise to poor in vitro-in vivo correlations because of the inadequacy of the buffer to resemble small intestinal fluids. A more representative and physiological medium, pH 6.8 bicarbonate buffer, was developed to evaluate the dissolution behaviour of enteric coatings. The bicarbonate system was evolved from pH 7.4 Hanks balanced salt solution to produce a pH 6.8 bicarbonate buffer (modified Hanks buffer, mHanks), which resembles the ionic composition and buffer capacity of intestinal milieu. Prednisolone tablets were coated with a range of enteric polymers: hypromellose phthalate (HP-50 and HP-55), cellulose acetate phthalate (CAP), hypromellose acetate succinate (HPMCAS-LF and HPMCAS-MF), methacrylic acid copolymers (EUDRAGIT® L100-55, EUDRAGIT® L30D-55 and EUDRAGIT® L100) and polyvinyl acetate phthalate (PVAP). Dissolution of coated tablets was carried out using USP-II apparatus in 0.1 M HCl for 2 h followed by pH 6.8 phosphate buffer or pH 6.8 mHanks bicarbonate buffer. In pH 6.8 phosphate buffer, the various enteric polymer coated products displayed rapid and comparable dissolution profiles. In pH 6.8 mHanks buffer, drug release was delayed and marked differences were observed between the various coated tablets, which is comparable to the delayed disintegration times reported in the literature for enteric coated products in the human small intestine. In summary, the use of pH 6.8 physiological bicarbonate buffer (mHanks) provides more realistic and discriminative in vitro release assessment of enteric coated formulations compared to compendial phosphate buffer.
AB - The use of compendial pH 6.8 phosphate buffer to assess dissolution of enteric coated products gives rise to poor in vitro-in vivo correlations because of the inadequacy of the buffer to resemble small intestinal fluids. A more representative and physiological medium, pH 6.8 bicarbonate buffer, was developed to evaluate the dissolution behaviour of enteric coatings. The bicarbonate system was evolved from pH 7.4 Hanks balanced salt solution to produce a pH 6.8 bicarbonate buffer (modified Hanks buffer, mHanks), which resembles the ionic composition and buffer capacity of intestinal milieu. Prednisolone tablets were coated with a range of enteric polymers: hypromellose phthalate (HP-50 and HP-55), cellulose acetate phthalate (CAP), hypromellose acetate succinate (HPMCAS-LF and HPMCAS-MF), methacrylic acid copolymers (EUDRAGIT® L100-55, EUDRAGIT® L30D-55 and EUDRAGIT® L100) and polyvinyl acetate phthalate (PVAP). Dissolution of coated tablets was carried out using USP-II apparatus in 0.1 M HCl for 2 h followed by pH 6.8 phosphate buffer or pH 6.8 mHanks bicarbonate buffer. In pH 6.8 phosphate buffer, the various enteric polymer coated products displayed rapid and comparable dissolution profiles. In pH 6.8 mHanks buffer, drug release was delayed and marked differences were observed between the various coated tablets, which is comparable to the delayed disintegration times reported in the literature for enteric coated products in the human small intestine. In summary, the use of pH 6.8 physiological bicarbonate buffer (mHanks) provides more realistic and discriminative in vitro release assessment of enteric coated formulations compared to compendial phosphate buffer.
KW - pH-sensitive polymers
KW - enteric polymers
KW - enteric coatings
KW - modified release
KW - physiological buffers
KW - bicarbonate media
KW - biorelevant dissolution
U2 - 10.1016/j.ejpb.2011.01.001
DO - 10.1016/j.ejpb.2011.01.001
M3 - Article
SN - 0939-6411
VL - 78
SP - 151
EP - 157
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
IS - 1
ER -