The effect of pH and ionic strength of dissolution media on in-vitro release of two model drugs of different solubilities from HPMC matrices

Kofi Asare-Addo, Barbara R Conway, El Hassanne Larhrib, Marina Levina, Ali R Rajabi-Siahboomi, John Tetteh, Joshua Boateng, Ali Nokhodchi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The evaluation of the effects of different media ionic strengths and pH on the release of hydrochlorothiazide, a poorly soluble drug, and diltiazem hydrochloride, a cationic and soluble drug, from a gel forming hydrophilic polymeric matrix was the objective of this study. The drug to polymer ratio of formulated tablets was 4:1. Hydrochlorothiazide or diltiazem HCl 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 strength of the media was varied over a range of 0-0.4M 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 strength had a profound effect on the drug release from the diltiazem HCl K100LV matrices. The K4M, K15M and K100M tablets however withstood the effects of media ionic strength and showed a decrease in drug release to occur with an increase in ionic strength. For example, drug release after the 1h mark for the K100M matrices in water was 36%. Drug release in pH 1.2 after 1h was 30%. An increase of the pH 1.2 ionic strength to 0.4M saw a reduction of drug release to 26%. This was the general trend for the K4M and K15M matrices as well. The similarity factor f2 was calculated using drug release in water as a reference. Despite similarity occurring for all the diltiazem HCl matrices in the pH 1.2 media (f2=64-72), increases of ionic strength at 0.2M and 0.4M brought about dissimilarity. The hydrochlorothiazide tablet matrices showed similarity at all the ionic strength tested for all polymers (f2=56-81). The values of f2 however reduced with increasing ionic strengths. DSC hydration results explained the hydrochlorothiazide release from their HPMC matrices. There was an increase in bound water as ionic strengths increased. Texture analysis was employed to determine the gel strength and also to explain the drug release for the diltiazem hydrochloride. 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
Pages384-91
Number of pages8
JournalColloids and Surfaces B: Biointerfaces
Volume111
DOIs
Publication statusPublished - 1 Nov 2013

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Ionic strength
Osmolar Concentration
Solubility
dissolving
Dissolution
drugs
solubility
Diltiazem
matrices
Hydrochlorothiazide
Pharmaceutical Preparations
tablets
Tablets
Polymers
hydrochlorides
Water
Gels
polymers
Hypromellose Derivatives
In Vitro Techniques

Cite this

@article{d2d56a39e9ba416eabd31a538cf37912,
title = "The effect of pH and ionic strength of dissolution media on in-vitro release of two model drugs of different solubilities from HPMC matrices",
abstract = "The evaluation of the effects of different media ionic strengths and pH on the release of hydrochlorothiazide, a poorly soluble drug, and diltiazem hydrochloride, a cationic and soluble drug, from a gel forming hydrophilic polymeric matrix was the objective of this study. The drug to polymer ratio of formulated tablets was 4:1. Hydrochlorothiazide or diltiazem HCl 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 strength of the media was varied over a range of 0-0.4M 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 strength had a profound effect on the drug release from the diltiazem HCl K100LV matrices. The K4M, K15M and K100M tablets however withstood the effects of media ionic strength and showed a decrease in drug release to occur with an increase in ionic strength. For example, drug release after the 1h mark for the K100M matrices in water was 36{\%}. Drug release in pH 1.2 after 1h was 30{\%}. An increase of the pH 1.2 ionic strength to 0.4M saw a reduction of drug release to 26{\%}. This was the general trend for the K4M and K15M matrices as well. The similarity factor f2 was calculated using drug release in water as a reference. Despite similarity occurring for all the diltiazem HCl matrices in the pH 1.2 media (f2=64-72), increases of ionic strength at 0.2M and 0.4M brought about dissimilarity. The hydrochlorothiazide tablet matrices showed similarity at all the ionic strength tested for all polymers (f2=56-81). The values of f2 however reduced with increasing ionic strengths. DSC hydration results explained the hydrochlorothiazide release from their HPMC matrices. There was an increase in bound water as ionic strengths increased. Texture analysis was employed to determine the gel strength and also to explain the drug release for the diltiazem hydrochloride. 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 = "Calorimetry, Differential Scanning, Delayed-Action Preparations, Diltiazem, Hydrochlorothiazide, Hydrogen-Ion Concentration, Hypromellose Derivatives, Osmolar Concentration, Solubility, Journal Article",
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note = "Copyright {\circledC} 2013 Elsevier B.V. All rights reserved.",
year = "2013",
month = "11",
day = "1",
doi = "10.1016/j.colsurfb.2013.06.034",
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The effect of pH and ionic strength of dissolution media on in-vitro release of two model drugs of different solubilities from HPMC matrices. / Asare-Addo, Kofi; Conway, Barbara R; Larhrib, El Hassanne; Levina, Marina; Rajabi-Siahboomi, Ali R; Tetteh, John; Boateng, Joshua; Nokhodchi, Ali.

In: Colloids and Surfaces B: Biointerfaces, Vol. 111, 01.11.2013, p. 384-91.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The effect of pH and ionic strength of dissolution media on in-vitro release of two model drugs of different solubilities from HPMC matrices

AU - Asare-Addo, Kofi

AU - Conway, Barbara R

AU - Larhrib, El Hassanne

AU - Levina, Marina

AU - Rajabi-Siahboomi, Ali R

AU - Tetteh, John

AU - Boateng, Joshua

AU - Nokhodchi, Ali

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - The evaluation of the effects of different media ionic strengths and pH on the release of hydrochlorothiazide, a poorly soluble drug, and diltiazem hydrochloride, a cationic and soluble drug, from a gel forming hydrophilic polymeric matrix was the objective of this study. The drug to polymer ratio of formulated tablets was 4:1. Hydrochlorothiazide or diltiazem HCl 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 strength of the media was varied over a range of 0-0.4M 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 strength had a profound effect on the drug release from the diltiazem HCl K100LV matrices. The K4M, K15M and K100M tablets however withstood the effects of media ionic strength and showed a decrease in drug release to occur with an increase in ionic strength. For example, drug release after the 1h mark for the K100M matrices in water was 36%. Drug release in pH 1.2 after 1h was 30%. An increase of the pH 1.2 ionic strength to 0.4M saw a reduction of drug release to 26%. This was the general trend for the K4M and K15M matrices as well. The similarity factor f2 was calculated using drug release in water as a reference. Despite similarity occurring for all the diltiazem HCl matrices in the pH 1.2 media (f2=64-72), increases of ionic strength at 0.2M and 0.4M brought about dissimilarity. The hydrochlorothiazide tablet matrices showed similarity at all the ionic strength tested for all polymers (f2=56-81). The values of f2 however reduced with increasing ionic strengths. DSC hydration results explained the hydrochlorothiazide release from their HPMC matrices. There was an increase in bound water as ionic strengths increased. Texture analysis was employed to determine the gel strength and also to explain the drug release for the diltiazem hydrochloride. 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 evaluation of the effects of different media ionic strengths and pH on the release of hydrochlorothiazide, a poorly soluble drug, and diltiazem hydrochloride, a cationic and soluble drug, from a gel forming hydrophilic polymeric matrix was the objective of this study. The drug to polymer ratio of formulated tablets was 4:1. Hydrochlorothiazide or diltiazem HCl 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 strength of the media was varied over a range of 0-0.4M 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 strength had a profound effect on the drug release from the diltiazem HCl K100LV matrices. The K4M, K15M and K100M tablets however withstood the effects of media ionic strength and showed a decrease in drug release to occur with an increase in ionic strength. For example, drug release after the 1h mark for the K100M matrices in water was 36%. Drug release in pH 1.2 after 1h was 30%. An increase of the pH 1.2 ionic strength to 0.4M saw a reduction of drug release to 26%. This was the general trend for the K4M and K15M matrices as well. The similarity factor f2 was calculated using drug release in water as a reference. Despite similarity occurring for all the diltiazem HCl matrices in the pH 1.2 media (f2=64-72), increases of ionic strength at 0.2M and 0.4M brought about dissimilarity. The hydrochlorothiazide tablet matrices showed similarity at all the ionic strength tested for all polymers (f2=56-81). The values of f2 however reduced with increasing ionic strengths. DSC hydration results explained the hydrochlorothiazide release from their HPMC matrices. There was an increase in bound water as ionic strengths increased. Texture analysis was employed to determine the gel strength and also to explain the drug release for the diltiazem hydrochloride. 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 - Calorimetry, Differential Scanning

KW - Delayed-Action Preparations

KW - Diltiazem

KW - Hydrochlorothiazide

KW - Hydrogen-Ion Concentration

KW - Hypromellose Derivatives

KW - Osmolar Concentration

KW - Solubility

KW - Journal Article

U2 - 10.1016/j.colsurfb.2013.06.034

DO - 10.1016/j.colsurfb.2013.06.034

M3 - Article

VL - 111

SP - 384

EP - 391

JO - Colloids and Surfaces B: Biointerfaces

T2 - Colloids and Surfaces B: Biointerfaces

JF - Colloids and Surfaces B: Biointerfaces

SN - 0927-7765

ER -