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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.
Colloids Surf B Biointerfaces. 2013 Nov 01; 111:384-91.CS

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.

Authors+Show Affiliations

Pharmacy and Pharmaceutical Science, University of Huddersfield, Huddersfield HD1 3DH, UK.Pharmacy and Pharmaceutical Science, University of Huddersfield, Huddersfield HD1 3DH, UK.Pharmacy and Pharmaceutical Science, University of Huddersfield, Huddersfield HD1 3DH, UK.Colorcon Ltd, Flagship House, Victory Way, Crossways, Dartford, Kent DA2 6QD, UK.Colorcon Ltd, Flagship House, Victory Way, Crossways, Dartford, Kent DA2 6QD, UK.Department of Pharmaceutical, Chemical and Environmental Science, School of Science, University of Greenwich, Kent ME4 4TB, UK.Department of Pharmaceutical, Chemical and Environmental Science, School of Science, University of Greenwich, Kent ME4 4TB, UK.Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, Kent ME4 4TB, UK; Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: a.nokhodchi@kent.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23850747

Citation

Asare-Addo, Kofi, et al. "The Effect of pH and Ionic Strength of Dissolution Media On In-vitro Release of Two Model Drugs of Different Solubilities From HPMC Matrices." Colloids and Surfaces. B, Biointerfaces, vol. 111, 2013, pp. 384-91.
Asare-Addo K, Conway BR, Larhrib H, et al. The effect of pH and ionic strength of dissolution media on in-vitro release of two model drugs of different solubilities from HPMC matrices. Colloids Surf B Biointerfaces. 2013;111:384-91.
Asare-Addo, K., Conway, B. R., Larhrib, H., Levina, M., Rajabi-Siahboomi, A. R., Tetteh, J., Boateng, J., & Nokhodchi, A. (2013). The effect of pH and ionic strength of dissolution media on in-vitro release of two model drugs of different solubilities from HPMC matrices. Colloids and Surfaces. B, Biointerfaces, 111, 384-91. https://doi.org/10.1016/j.colsurfb.2013.06.034
Asare-Addo K, et al. The Effect of pH and Ionic Strength of Dissolution Media On In-vitro Release of Two Model Drugs of Different Solubilities From HPMC Matrices. Colloids Surf B Biointerfaces. 2013 Nov 1;111:384-91. PubMed PMID: 23850747.
* Article titles in AMA citation format should be in sentence-case
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,Hassan, AU - Levina,Marina, AU - Rajabi-Siahboomi,Ali R, AU - Tetteh,John, AU - Boateng,Joshua, AU - Nokhodchi,Ali, Y1 - 2013/06/25/ PY - 2013/02/11/received PY - 2013/06/12/revised PY - 2013/06/17/accepted PY - 2013/7/16/entrez PY - 2013/7/16/pubmed PY - 2015/7/3/medline KW - Diltiazem HCl KW - HPMC polymeric matrix tablets KW - Hydration KW - Hydrochlorothiazide KW - Ionic strength KW - Kinetics of drug release KW - Similarity factor SP - 384 EP - 91 JF - Colloids and surfaces. B, Biointerfaces JO - Colloids Surf B Biointerfaces VL - 111 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. SN - 1873-4367 UR - https://www.unboundmedicine.com/medline/citation/23850747/The_effect_of_pH_and_ionic_strength_of_dissolution_media_on_in_vitro_release_of_two_model_drugs_of_different_solubilities_from_HPMC_matrices_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0927-7765(13)00410-4 DB - PRIME DP - Unbound Medicine ER -