The solubility of weakly basic drugs within passage though GI tract leads to pH-dependent or even incomplete release of these drugs from extended release formulations and consequently to lower drug absorption and bioavailability. The aim of the study was to prepare and evaluate hydrophilic-lipophilic (hypromellose-montanglycol wax) matrix tablets ensuring the pH-independent delivery of the weakly basic drug verapamil-hydrochloride by an incorporation of three organic acidifiers (citric, fumaric, and itaconic acids) differing in their concentrations, pK a, and solubility. The dissolution studies were performed by the method of changing pH values, which better corresponded to the real conditions in the GI tract (2 h at pH 1.2 and then 10 h at pH 6.8). Within the same conditions, pH of matrix microenvironment was measured. To determine relationships between the above mentioned properties of acidifiers and the monitored effects (the amount of released drug and surface pH of gel layer in selected time intervals-360 and 480 min), the full factorial design method and partial least squares PLS-2 regression were used. The incorporation of the tested pH modifiers significantly increased the drug release rate from matrices. PLS-components explained 75% and 73% variation in the X- and Y-data, respectively. The obtained results indicated that the main crucial points (p < 0.01) were the concentration and strength of acidifier incorporated into the matrix. Contrary, the acid solubility surprisingly did not influence the selected effects except for the surface pH of gel layer in time 480 min.

• MeSH
• Algorithms MeSH
• Calcium Channel Blockers administration & dosage   chemistry   MeSH
• Hypromellose Derivatives MeSH
• Electrodes MeSH
• Factor Analysis, Statistical MeSH
• Gels MeSH
• Kinetics MeSH
• Hydrogen-Ion Concentration MeSH
• Pharmaceutical Preparations administration & dosage   chemistry   MeSH
• Methylcellulose analogs & derivatives   MeSH
• Drug Design MeSH
• Solubility MeSH
• Tablets MeSH
• Particle Size MeSH
• Verapamil administration & dosage   chemistry   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Calcium Channel Blockers MeSH
• Hypromellose Derivatives MeSH
• Gels MeSH
• Pharmaceutical Preparations MeSH
• Methylcellulose MeSH
• Tablets MeSH
• Verapamil MeSH