Agitation Sequence and Ionic Strength on In-Vitro Drug Release from Hypromellose –The Influence of Compaction Force

The evaluations of the systematic effects of agitation and ionic strength and its impact on tablet compression force on the drug release from a gel forming matrix were the objectives of this study. To achieve this, two model drugs namely, theophylline and diltiazem HCl were formulated with hydroxypropyl methyl cellulose into matrix tablets and the drug release in a range of pHs 1.2-7.5 was evaluated using the automated USP type III Bio-Dis Varian. The effects of agitation were investigated at 10, 20 and in an ascending and descending order in the vials. Agitation had a profound effect on the drug release from the K100LV tablet matrices. Ionic strength was investigated using NaCl as the ionic strength regulator. A range of 0-0.4 M ionic strengths were studied. It was noticed that an increase in the compression of the tablet matrices for the K100LV theophylline and diltiazem HCl tablet matrices resulted in a significant difference in their drug release profiles both in the agitation sequence and with the influence of ionic concentration strength. The K100M tablet matrices for the theophylline and diltiazem HCl on the other hand were generally unaffected. This investigation also highlights the importance of controlling drug release in the desired dissolution medium as agitation could significantly influence the drug release resulting in a possible toxicity or making drug not available at the required site.

Keywords: HPMC, theophylline, diltiazem hydrochloride, ionic strength, agitation, compression, USP III Bio-Dis