TY - JOUR
T1 - Effect of ionic strength and pH of dissolution media on theophylline release from hypromellose matrix tablets - Apparatus USP III, simulated fasted and fed conditions
AU - Asare-Addo, Kofi
AU - Levina, Marina
AU - Rajabi-Siahboomi, Ali R.
AU - Nokhodchi, Ali
PY - 2011/8/1
Y1 - 2011/8/1
N2 - The objectives of this study were to evaluate the effects of different media ionic concentration strengths and pH on the release of theophylline from a gel forming hydrophilic polymeric matrix. Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC)) were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The ionic concentration strength of the media was varied over a range of 0-0.4 M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. Sodium chloride was used for ionic regulation due to its ability to salt out polymers in the midrange of the lyotropic series. The results showed that the ionic concentration strength had a profound effect on the drug release from the K100LV matrices. At pH 1.2 theophylline releases increased significantly within the first hour from 28% in water to 48% in the medium with ionic strength of 0.49 M. The K4M, K15M and K100M tablets, however, withstood the effects of media to the same extend at all ionic concentration strengths investigated. The similarity factor f2 was calculated using drug release in water as a reference. For the K100M matrices, f2 values of 74 (pH media), 80 (0.2 M media) and 72 (0.4 M media) suggested that it was the most resilient of all the matrices studied here. DSC hydration results explained the theophylline release from their HPMC matrices. Despite an increase in the percentage of bound water for the tablets made with high viscosity polymers K4M, K15M and K100M, they were, however, resilient to the ionic concentration strength effects as they were still able to form a strong gel layer. This methodology can be used as a valuable tool for predicting potential ionic effects related to in vivo fed and fasted states on drug release from hydrophilic ER matrices.
AB - The objectives of this study were to evaluate the effects of different media ionic concentration strengths and pH on the release of theophylline from a gel forming hydrophilic polymeric matrix. Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC)) were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The ionic concentration strength of the media was varied over a range of 0-0.4 M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. Sodium chloride was used for ionic regulation due to its ability to salt out polymers in the midrange of the lyotropic series. The results showed that the ionic concentration strength had a profound effect on the drug release from the K100LV matrices. At pH 1.2 theophylline releases increased significantly within the first hour from 28% in water to 48% in the medium with ionic strength of 0.49 M. The K4M, K15M and K100M tablets, however, withstood the effects of media to the same extend at all ionic concentration strengths investigated. The similarity factor f2 was calculated using drug release in water as a reference. For the K100M matrices, f2 values of 74 (pH media), 80 (0.2 M media) and 72 (0.4 M media) suggested that it was the most resilient of all the matrices studied here. DSC hydration results explained the theophylline release from their HPMC matrices. Despite an increase in the percentage of bound water for the tablets made with high viscosity polymers K4M, K15M and K100M, they were, however, resilient to the ionic concentration strength effects as they were still able to form a strong gel layer. This methodology can be used as a valuable tool for predicting potential ionic effects related to in vivo fed and fasted states on drug release from hydrophilic ER matrices.
KW - DSC
KW - HPMC polymeric matrix tablets
KW - Hydration
KW - Ionic concentration strength
KW - Kinetics of drug release
KW - Similarity factor
UR - http://www.scopus.com/inward/record.url?scp=79959334645&partnerID=8YFLogxK
UR - https://www.journals.elsevier.com/carbohydrate-polymers
U2 - 10.1016/j.carbpol.2011.04.014
DO - 10.1016/j.carbpol.2011.04.014
M3 - Article
AN - SCOPUS:79959334645
VL - 86
SP - 85
EP - 93
JO - Carbohydrate Polymers
JF - Carbohydrate Polymers
SN - 0144-8617
IS - 1
ER -