Formulations of zero-order, pH-dependent, sustained release matrix systems by ionotropic gelation of alginate-containing mixtures

Abstract

Background: Matrix type, monolithic, dosage forms suitable for controlled release that exhibit pH-dependent behavior are considerably less common than similarly behaving multiparticulated, enterically coated dosage forms, although simpler and less expensive to make. Aim: Evaluate the properties of alginates and alginate-containing systems to produce pH-sensitive, monolithic, controlled release dosage forms that perform acceptably and determine their limits of application in regard with stability, pH and Ca⁺⁺ sensitivity, and appropriated rate of release. Method: Mixtures of the ionic gum sodium alginate (Na Alg.) with other gel-forming gums such as propylene glycol alginate (PGA), xanthan, or hydroxypropyl methylcellulose have been evaluated for applicability in the manufacture of controlled release dosage forms with three drugs of different solubility and ionic character. Mixture have been compressed into tablets and tested under a variety of pHs to simulate transit through the GI tract, in the presence of Ca⁺⁺, and for stability. Results: These mixtures have been able to sustain drug release for up to 12 hours with acceptable performance going from acidic to alkaline pHs to simulate travel through the GI tract and in the presence of Ca⁺⁺. Release rate has been adjusted by selecting a suitable Na Alg./other gum combination at an appropriated ratio. Conclusions: Mixtures of Na Alg. with a number of other gums have been demonstrated suitable to manufacture pH‐sensitive, matrix-type solid dosage forms with release-controlling properties for up to 12 hours.

• Algin
• hydroxypropyl methyl cellulose
• pH dependent
• propylene glycol alginate
• sodium alginate
• solid dosage forms
• sustained release
• xanthan gum