Fexofenadine Hydrochloride

The current study aimed to explore the impact of buffer species on the dissolution behavior of orally disintegrating tablets (ODT) containing a basic polymer and its influence on bioequivalence (BE) prediction. Fexofenadine hydrochloride ODT formulations were used as the model formulations, Allegra^® as the reference formulation, and generic formulations A and B as the test formulations. Allegra^®, generic A, and generic B are ODT formulations that contain aminoalkyl methacrylate copolymers E (Eudragit^® E, EUD-E), a basic polymer commonly used to mask the bitter taste of drugs. Both generic A and generic B have been known to be bioequivalent to Allegra^®. The dissolution tests were conducted using a compendial paddle, with either bicarbonate (10 mM, pH 6.8) or phosphate buffer (25 mM, pH 6.8) as the dissolution media. A floating lid was employed to cover the surface of the bicarbonate buffer to prevent volatilization. Results indicated that in phosphate buffer, the dissolution profiles of Allegra and generic B significantly varied from that of generic A, whereas in the bicarbonate buffer, the dissolution profiles of Allegra, generic A, and generic B were comparable. These findings suggest that the use of bicarbonate buffer may offer a more precise prediction of human bioequivalence compared to phosphate buffer.

Wet granulation (WG) is one of the most versatile processes to improve blend properties for processing. However, due to its need for moisture and heat, it is often considered not amenable to active pharmaceutical ingredients (APIs) prone to forming hydrates. Despite this claim, little literature exists evaluating the extent to which polymorphic form conversions occur for such API when processed with WG. This work sets out to explore two common WG methods, high-shear (HSG) and fluid-bed (FBG), and two drying processes, tray-drying (TD) and fluid-bed drying (FBD), and evaluate the risk they pose to hydrate form conversion.

The progression of anhydrous to hydrate form conversion of two model compounds with vastly different solubilities, fexofenadine hydrochloride and carbamazepine, was monitored throughout the various processes using powder X-ray diffraction. The resultant granules were characterized using thermogravimetric analysis, differential scanning calorimetry, BET adsorption, and sieve analysis.

FBG and FBD processing resulted in the preservation of the original form of both APIs, while HSG+TD resulted in the complete conversion of the API. The FBD of fexofenadine and carbamazepine granules prepared with HSG resulted in partial and complete re-conversion back to the original anhydrous forms, respectively.

The drying process is a critical factor in anhydrous form conservation. FBG and FBD yielded better preservation of the initial anhydrous forms. HSG could be an acceptable granulation method for API susceptible to hydrate formation if the API solubility is low. Selecting an FBG+FBD process minimizes API hydrate formation and preserves the original anhydrous form.