Role of Cyclodextrins and Drug Solid State Properties on Flufenamic Acid Dissolution Performance from Tablets

Abstract

Flufenamic acid (FFA) is a non-steroidal anti-inflammatory drug characterised by a low solubility and problems of variable dissolution rate and bio-inequivalence. Different FFA batches, obtained by different suppliers, showed different powder characteristics (particle size, shape and surface properties) that may affect its dissolution behaviour from solid dosage forms. Aim of this work was the improvement of FFA solubility and dissolution rate by the use of cyclodextrins (CDs) and the obtainment of an effective tablet formulation by direct compression. Several CDs have been tested, both in solution and in solid state and several binary systems drug-CDs have been obtained with different techniques, with the scope to select the most effective system. Grinding technique with randomly methylated-β-cyclodextrin (RAMEB) was the only one that allowed the complete drug amorphization, together with the highest improvement in drug dissolution rate, and was then selected for tablets formulation. Conventional and immediate release tablets were obtained and fully characterised for technological properties. In both cases an improved and well reproducible drug dissolution performance was obtained, independently from the FFA supplier and thus no more affected by the differences observed between the original FFA crystalline samples.

Formulation of Pharmaceutical Tablets Containing β-Cyclodextrin-4-Methyl-Umbelliferone (Hymecromone) Inclusion Complexes and Study of the Dissolution Kinetics

“…In the same research, docking studies revealed that umbelliferone was not completely inserted into the α-CD cavity in all poses because of its small cavity size [9]. In the research studies of M. Novac et al [16] and F. Maestrelli et al [17], β-CD and various β-CD's derivatives (2-hydroxypropyl-β-cyclodextrin, (HP-β-CD), randomly methylated-β-CD (RAMEB), and sulfobutylether-β-CD (SBE-β-CD)), in the form of inclusion complexes with APIs such as nimodipine (calcium channel blocker [16]) and flufenamic acid (non-steroidal anti-inflammatory agent [17]), have been incorporated in pharmaceutical tablets via direct compression. The complexation of flufenamic acid with RAMEB remarkably improved its dissolution rate, being a useful tool for the effective Encapsulation is a common technique that is used to protect the encapsulated compounds from adverse environments, and to modify the physicochemical properties of different hydrophobic molecules such as their aqueous solubility and biological profile.…”