The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices-The use of the USP III apparatus

Kofi Asare-Addo, Waseem Kaialy, Marina Levina, Ali Rajabi-Siahboomi, Mohammed U. Ghori, Enes Supuk, Peter R. Laity, Barbara R. Conway, Ali Nokhodchi

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC) E4M and K4M were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The objectives of this study were to evaluate the effects of systematic agitation, ionic strength and pH on the release of theophylline from the gel forming hydrophilic polymeric matrices with different methoxyl substitution levels. Tribo-electric charging of hypromellose, theophylline and their formulated blends containing E4M and K4M grades has been characterised, along with quantitative observations of flow, compression behaviour and particle morphology. Agitations were studied at 5, 10, 15, 20, 25, 30 dips per minute (dpm) and also in the ascending and descending order in the dissolution vials. The ionic concentration strength of the media was also varied over a range of 0-0.4. M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. To study the effect of ionic strength on the hydrophilic matrices, agitation was set at 20 dpm. The charge results on individual components imply that the positively charged particles have coupled with the negatively charged particles to form a stable ordered mixture which is believed to result in a more homogeneous and stable system. The particle shape analysis showed the HPMC K4M polymer to have a more irregular morphology and a rougher surface texture in comparison to the HPMC E4M polymer, possibly a contributory factor to the gelation process. The results showed gelation occurred quicker for the K4M tablet matrices. Drug release increased with increased agitation. This was more pronounced for the E4M tablet matrices. The ionic strength also had more of an effect on the drug release from the E4M matrices. The experiments highlighted the resilience of the K4M matrices in comparison with the E4M matrices. The results thus show that despite similar viscosities of E4M and K4M, the methoxyl substitution makes a difference to their control of drug release and as such care and consideration should be given to the choice of polymer used for extended release. The use of systematic change of agitation method and ionic strength may indicate potential fed and fasted effects on drug release from hydrophilic matrices.

LanguageEnglish
Pages54-60
Number of pages7
JournalColloids and Surfaces B: Biointerfaces
Volume104
DOIs
Publication statusPublished - 1 Apr 2013

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agitation
Ionic strength
Osmolar Concentration
drugs
Theophylline
Gelation
Charged particles
matrices
Polymers
Pharmaceutical Preparations
Dissolution
Substitution reactions
Tablets
tablets
gelation
Gels
Viscosity
Textures
dissolving
charged particles

Cite this

@article{0756086d2af943909337197969508f14,
title = "The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices-The use of the USP III apparatus",
abstract = "Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC) E4M and K4M were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The objectives of this study were to evaluate the effects of systematic agitation, ionic strength and pH on the release of theophylline from the gel forming hydrophilic polymeric matrices with different methoxyl substitution levels. Tribo-electric charging of hypromellose, theophylline and their formulated blends containing E4M and K4M grades has been characterised, along with quantitative observations of flow, compression behaviour and particle morphology. Agitations were studied at 5, 10, 15, 20, 25, 30 dips per minute (dpm) and also in the ascending and descending order in the dissolution vials. The ionic concentration strength of the media was also varied over a range of 0-0.4. M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. To study the effect of ionic strength on the hydrophilic matrices, agitation was set at 20 dpm. The charge results on individual components imply that the positively charged particles have coupled with the negatively charged particles to form a stable ordered mixture which is believed to result in a more homogeneous and stable system. The particle shape analysis showed the HPMC K4M polymer to have a more irregular morphology and a rougher surface texture in comparison to the HPMC E4M polymer, possibly a contributory factor to the gelation process. The results showed gelation occurred quicker for the K4M tablet matrices. Drug release increased with increased agitation. This was more pronounced for the E4M tablet matrices. The ionic strength also had more of an effect on the drug release from the E4M matrices. The experiments highlighted the resilience of the K4M matrices in comparison with the E4M matrices. The results thus show that despite similar viscosities of E4M and K4M, the methoxyl substitution makes a difference to their control of drug release and as such care and consideration should be given to the choice of polymer used for extended release. The use of systematic change of agitation method and ionic strength may indicate potential fed and fasted effects on drug release from hydrophilic matrices.",
keywords = "Agitation, DSC, HPMC, Ionic concentration strength, Kinetics of drug release, Particle size, Similarity factor, Theophylline, Triboelectrification, USP III",
author = "Kofi Asare-Addo and Waseem Kaialy and Marina Levina and Ali Rajabi-Siahboomi and Ghori, {Mohammed U.} and Enes Supuk and Laity, {Peter R.} and Conway, {Barbara R.} and Ali Nokhodchi",
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The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices-The use of the USP III apparatus. / Asare-Addo, Kofi; Kaialy, Waseem; Levina, Marina; Rajabi-Siahboomi, Ali; Ghori, Mohammed U.; Supuk, Enes; Laity, Peter R.; Conway, Barbara R.; Nokhodchi, Ali.

In: Colloids and Surfaces B: Biointerfaces, Vol. 104, 01.04.2013, p. 54-60.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices-The use of the USP III apparatus

AU - Asare-Addo, Kofi

AU - Kaialy, Waseem

AU - Levina, Marina

AU - Rajabi-Siahboomi, Ali

AU - Ghori, Mohammed U.

AU - Supuk, Enes

AU - Laity, Peter R.

AU - Conway, Barbara R.

AU - Nokhodchi, Ali

PY - 2013/4/1

Y1 - 2013/4/1

N2 - Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC) E4M and K4M were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The objectives of this study were to evaluate the effects of systematic agitation, ionic strength and pH on the release of theophylline from the gel forming hydrophilic polymeric matrices with different methoxyl substitution levels. Tribo-electric charging of hypromellose, theophylline and their formulated blends containing E4M and K4M grades has been characterised, along with quantitative observations of flow, compression behaviour and particle morphology. Agitations were studied at 5, 10, 15, 20, 25, 30 dips per minute (dpm) and also in the ascending and descending order in the dissolution vials. The ionic concentration strength of the media was also varied over a range of 0-0.4. M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. To study the effect of ionic strength on the hydrophilic matrices, agitation was set at 20 dpm. The charge results on individual components imply that the positively charged particles have coupled with the negatively charged particles to form a stable ordered mixture which is believed to result in a more homogeneous and stable system. The particle shape analysis showed the HPMC K4M polymer to have a more irregular morphology and a rougher surface texture in comparison to the HPMC E4M polymer, possibly a contributory factor to the gelation process. The results showed gelation occurred quicker for the K4M tablet matrices. Drug release increased with increased agitation. This was more pronounced for the E4M tablet matrices. The ionic strength also had more of an effect on the drug release from the E4M matrices. The experiments highlighted the resilience of the K4M matrices in comparison with the E4M matrices. The results thus show that despite similar viscosities of E4M and K4M, the methoxyl substitution makes a difference to their control of drug release and as such care and consideration should be given to the choice of polymer used for extended release. The use of systematic change of agitation method and ionic strength may indicate potential fed and fasted effects on drug release from hydrophilic matrices.

AB - Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC) E4M and K4M were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The objectives of this study were to evaluate the effects of systematic agitation, ionic strength and pH on the release of theophylline from the gel forming hydrophilic polymeric matrices with different methoxyl substitution levels. Tribo-electric charging of hypromellose, theophylline and their formulated blends containing E4M and K4M grades has been characterised, along with quantitative observations of flow, compression behaviour and particle morphology. Agitations were studied at 5, 10, 15, 20, 25, 30 dips per minute (dpm) and also in the ascending and descending order in the dissolution vials. The ionic concentration strength of the media was also varied over a range of 0-0.4. M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. To study the effect of ionic strength on the hydrophilic matrices, agitation was set at 20 dpm. The charge results on individual components imply that the positively charged particles have coupled with the negatively charged particles to form a stable ordered mixture which is believed to result in a more homogeneous and stable system. The particle shape analysis showed the HPMC K4M polymer to have a more irregular morphology and a rougher surface texture in comparison to the HPMC E4M polymer, possibly a contributory factor to the gelation process. The results showed gelation occurred quicker for the K4M tablet matrices. Drug release increased with increased agitation. This was more pronounced for the E4M tablet matrices. The ionic strength also had more of an effect on the drug release from the E4M matrices. The experiments highlighted the resilience of the K4M matrices in comparison with the E4M matrices. The results thus show that despite similar viscosities of E4M and K4M, the methoxyl substitution makes a difference to their control of drug release and as such care and consideration should be given to the choice of polymer used for extended release. The use of systematic change of agitation method and ionic strength may indicate potential fed and fasted effects on drug release from hydrophilic matrices.

KW - Agitation

KW - DSC

KW - HPMC

KW - Ionic concentration strength

KW - Kinetics of drug release

KW - Particle size

KW - Similarity factor

KW - Theophylline

KW - Triboelectrification

KW - USP III

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U2 - 10.1016/j.colsurfb.2012.11.020

DO - 10.1016/j.colsurfb.2012.11.020

M3 - Article

VL - 104

SP - 54

EP - 60

JO - Colloids and Surfaces B: Biointerfaces

T2 - Colloids and Surfaces B: Biointerfaces

JF - Colloids and Surfaces B: Biointerfaces

SN - 0927-7765

ER -