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

The aim of this study was to develop novel hydrogel-based beads and characterize their potential to deliver and release a drug exhibiting pH-dependent solubility into distal parts of gastrointestinal (GI) tract. Oxycellulose beads containing diclofenac sodium as a model drug were prepared by the ionotropic external gelation technique using calcium chloride solution as the cross-linking medium. Resulting beads were characterized in terms of particle shape and size, encapsulation efficacy, swelling ability and in vitro drug release. Also, potential drug-polymer interactions were evaluated using Fourier transform infrared spectroscopy. The particle size was found to be 0.92-0.96 mm for inactive (oxycellulose only) and 1.47-1.60 mm for active (oxycellulose-diclofenac sodium) beads, respectively. In all cases, the sphericity factor was between 0.70 and 0.81 with higher values observed for samples containing higher polymer and drug concentrations. The swelling of inactive beads was found to be strongly influenced by the pH and composition (i.e. Na(+) concentration) of the selected media (simulated gastric fluid vs. phosphate buffer pH 6.8). The encapsulation efficiency of the prepared particles ranged from 58% to 65%. Results of dissolution tests showed that the drug loading inside of the particles influenced the rate of its release. In general, prepared particles were able to release the drug within 12-16 h after a lag time of 4 h. Fickian diffusion was found as the predominant drug release mechanism. Thus, this novel particulate system showed a good potential to deliver drugs specifically to the distal parts of the human GI tract.

• MeSH
• Anti-Inflammatory Agents, Non-Steroidal chemistry   MeSH
• Models, Chemical MeSH
• Hypromellose Derivatives MeSH
• Diffusion MeSH
• Diclofenac chemistry   MeSH
• Chemistry, Pharmaceutical MeSH
• Technology, Pharmaceutical methods   MeSH
• Kinetics MeSH
• Hydrogen-Ion Concentration MeSH
• Delayed-Action Preparations MeSH
• Methylcellulose analogs & derivatives   chemistry   MeSH
• Drug Carriers * MeSH
• Drug Compounding MeSH
• Buffers MeSH
• Solubility MeSH
• Spectroscopy, Fourier Transform Infrared MeSH
• Feasibility Studies MeSH
• Particle Size MeSH
• Gastric Juice chemistry   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Inflammatory Agents, Non-Steroidal MeSH
• Hypromellose Derivatives MeSH
• Diclofenac MeSH
• Delayed-Action Preparations MeSH
• Methylcellulose MeSH
• Drug Carriers * MeSH
• Buffers MeSH