Enhancement of the Oral Bioavailability of Fexofenadine Hydrochloride via Cremophor(®) El-Based Liquisolid Tablets.

PURPOSE: The current work aimed to develop promising Fexofenadine hydrochloride (FXD) liquisolid tablets able to increase its oral bioavailability and shorten time to reach maximum plasma concentrations (Tmax). METHODS: Eighteen liquisolid powders were developed based on 3 variables; (i) vehicle type [Propylene glycol (PG) or Cremophor(®) EL (CR)], (ii) carrier [Avicel(®) PH102] to coat [Aerosil(®) 200] ratio (15, 20, 25) and (iii) FXD concentration in vehicle (30, 35, 40 %, w/w). Pre-compression studies involved identification of physicochemical interactions and FXD crystallinity (FT-IR, DSC, XRD), topographic visualization (SEM) and estimation of flow properties (angle of repose, Carr's index, Hausner's ratio). CR-based liquisolid powders were compressed as liquisolid tablets (LST 9 - 18) and evaluated for weight-variation, drug-content, friability-percentage, disintegration-time and drug-release. The pharmacokinetics of LST-18 was evaluated in healthy volunteers relative to Allegra(®) tablets. RESULTS: Pre-compression studies confirmed FXD dispersion in vehicles, conversion to amorphous form and formation of liquisolid powders. CR-based liquisolid powders showed acceptable-to-good flow properties suitable for compaction. CR-based LSTs had appropriate physicochemical properties and short disintegration times. Release profile of LST-18 showed a complete drug release within 5 min. CONCLUSION: LST-18 succeeded in increasing oral FXD bioavailability by 62% and reducing Tmax to 2.16 h.

Phenylalanine-free taste-masked orodispersible tablets of fexofenadine hydrochloride: development, in vitro evaluation and in vivo estimation of the drug pharmacokinetics in healthy human volunteers.

CONTEXT: Fexofenadine hydrochloride (FXD) is a slightly soluble, bitter-tasting, drug having an oral bioavailability of 35%. The maximum plasma concentration is reached 2.6 h (T(max)) post-dose. OBJECTIVE: Developing taste-masked FXD orodispersible tablets (ODTs) to increase extent of drug absorption and reduce Tmax. METHODS: Taste masking was achieved via solid dispersion (SD) with chitosan (CS) or sodium alginate (ALG). Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction were performed to identify physicochemical interactions and FXD crystallinity. Taste-masked FXD-ODTs were developed via addition of superdisintegrants (croscarmellose sodium or sodium starch glycolate, 5% and 10%, w/w) or sublimable agents (camphor, menthol or thymol; 10% and 20%, w/w) to FXD-SDs. ODTs were evaluated for weight variation, drug-content, friability, wetting, disintegration and drug release. Camphor-based (20%, w/w) FXD-ODT (F12) was optimized (F23) by incorporation of a more hydrophilic lubricant (Pruv(®)), visualized via scanning electron microscopy and evaluated for FXD pharmacokinetics in healthy volunteers relative to Allegra(®) tablets. RESULTS: Based on gustatory sensation test, FXD-CS (1:1) and FXD-ALG (1:0.5) SDs were selected. Taste-masked FXD-ODTs had appropriate physicochemical properties. Drug release profiles of F23 and the phenylalanine-containing Allegra(®) ODT were similar (f(2) = 96). Pores were observed following camphor sublimation. The pharmacokinetic studies proved F23 ability to increase extent of FXD absorption and reduce T(max).