An Anti-Inflammatory Drug (Mefenamic Acid) Incorporated in Biodegradable Alginate Beads: Development and Optimization of the Process Using Factorial Design

Abstract

The objective of this study was to prepare and evaluate biodegradable alginate beads as a controlled-release system for a water-insoluble drug, mefenamic acid (MA), using 3 × 2² factorial design by ionotropic gelation method. Therefore, the mefenamic acid dispersion in a solution of alginate was dropped into the cross-linking CaCl₂ solution and a fairly high yield (71–89%) of MA-alginate beads were obtained. Their encapsulation efficiencies were in the range of 79.3–98.99%. The effect of drug:polymer ratio, CaCl₂ concentration, and curing time on the time for 50% of the drug to be released (t_50%), and the drug entrapment efficiency were evaluated with factorial design method. It was found that drug:polymer ratio and interaction of drug:polymer ratio and curing time had an important effect on the drug to be released (t_50%). The effect of CaCl₂ concentration is also important on the drug release. On the other hand, all factors except CaCl₂ concentration were effective on the drug entrapment efficiency. The swelling properties of beads were also studied. The release mechanism was described and found to be non-Fickian, Case II, and Super Case II transport for the formulations. This study suggested a new mefenamic acid alginate bead formulation for oral delivery of nonsteroidal anti-inflammatory drugs, which cause gastric irritation.

Keywords:

• alginate
• bead
• mefenamic acid
• factorial design
• controlled release