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.
authors.affiliation: Pharmacy and Pharmaceutical Science, University of Huddersfield, Huddersfield HD1 3DH, UK.
authors.forename: Kofi
authors.initials: K
authors.lastname: Asare-Addo
authors.affiliation: Pharmacy and Pharmaceutical Science, University of Huddersfield, Huddersfield HD1 3DH, UK.
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Conway
authors.affiliation: Pharmacy and Pharmaceutical Science, University of Huddersfield, Huddersfield HD1 3DH, UK.
authors.forename: Hassan
authors.initials: H
authors.lastname: Larhrib
authors.affiliation: Colorcon Ltd, Flagship House, Victory Way, Crossways, Dartford, Kent DA2 6QD, UK.
authors.forename: Marina
authors.initials: M
authors.lastname: Levina
authors.affiliation: Colorcon Ltd, Flagship House, Victory Way, Crossways, Dartford, Kent DA2 6QD, UK.
authors.forename: Ali R
authors.initials: AR
authors.lastname: Rajabi-Siahboomi
authors.affiliation: Department of Pharmaceutical, Chemical and Environmental Science, School of Science, University of Greenwich, Kent ME4 4TB, UK.
authors.forename: John
authors.initials: J
authors.lastname: Tetteh
authors.affiliation: Department of Pharmaceutical, Chemical and Environmental Science, School of Science, University of Greenwich, Kent ME4 4TB, UK.
authors.forename: Joshua
authors.initials: J
authors.lastname: Boateng
authors.affiliation: 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.
authors.forename: Ali
authors.initials: A
authors.lastname: Nokhodchi
mesh_terms: D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000494:pharmacology*; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives / Q000737:chemistry*; D009994:Osmolar Concentration; D012995:Solubility
chemical_list: D003692:Delayed-Action Preparations; D006852:Hydrochlorothiazide; D065347:Hypromellose Derivatives; D004110:Diltiazem
keywords: Diltiazem HCl; HPMC polymeric matrix tablets; Hydration; Hydrochlorothiazide; Ionic strength; Kinetics of drug release; Similarity factor