Effect of ionic strength and pH of dissolution media on theophylline release from hypromellose matrix tablets - Apparatus USP III, simulated fasted and fed conditions

Kofi Asare-Addo, Marina Levina, Ali R. Rajabi-Siahboomi, Ali Nokhodchi

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages85-93
Number of pages9
JournalCarbohydrate Polymers
Volume86
Issue number1
Early online date13 Apr 2011
DOIs
Publication statusPublished - 1 Aug 2011
Externally publishedYes

Fingerprint

Theophylline
Ionic strength
Tablets
Dissolution
Gels
Water
Polymers
Pharmaceutical Preparations
Sodium chloride
Hydration
Sodium Chloride
Viscosity
Salts
Hypromellose Derivatives
hydroxypropylmethylcellulose-lactose matrix

Cite this

@article{e5646c8fd82443a29c1f965ee60a2160,
title = "Effect of ionic strength and pH of dissolution media on theophylline release from hypromellose matrix tablets - Apparatus USP III, simulated fasted and fed conditions",
abstract = "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.",
keywords = "DSC, HPMC polymeric matrix tablets, Hydration, Ionic concentration strength, Kinetics of drug release, Similarity factor",
author = "Kofi Asare-Addo and Marina Levina and Rajabi-Siahboomi, {Ali R.} and Ali Nokhodchi",
year = "2011",
month = "8",
day = "1",
doi = "10.1016/j.carbpol.2011.04.014",
language = "English",
volume = "86",
pages = "85--93",
journal = "Carbohydrate Polymers",
issn = "0144-8617",
publisher = "Elsevier Limited",
number = "1",

}

Effect of ionic strength and pH of dissolution media on theophylline release from hypromellose matrix tablets - Apparatus USP III, simulated fasted and fed conditions. / Asare-Addo, Kofi; Levina, Marina; Rajabi-Siahboomi, Ali R.; Nokhodchi, Ali.

In: Carbohydrate Polymers, Vol. 86, No. 1, 01.08.2011, p. 85-93.

Research output: Contribution to journalArticle

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

VL - 86

SP - 85

EP - 93

JO - Carbohydrate Polymers

T2 - Carbohydrate Polymers

JF - Carbohydrate Polymers

SN - 0144-8617

IS - 1

ER -