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.
BACKGROUND
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).
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University , Cairo , Egypt .
Soad Ali
SA
Yehia
Mohamed Shafik
MS
El-Ridi
Mina Ibrahim
MI
Tadros
Nolwa Gamal
NG
El-Sherif
D000284:Administration, Oral; D000328:Adult; D000464:Alginates / Q000737:chemistry*; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D048271:Chitosan / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D008297:Male; D010649:Phenylalanine / Q000737:chemistry; D013607:Tablets; D013649:Taste; D055697:Taste Perception; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D055815:Young Adult
D000464:Alginates; D018926:Anti-Allergic Agents; D005079:Excipients; D006603:Hexuronic Acids; D013607:Tablets; D010649:Phenylalanine; D016593:Terfenadine; D020723:Glucuronic Acid; D048271:Chitosan; C093230:fexofenadine
Drug pharmacokinetics; fexofenadine hydrochloride; orodispersible tablets; phenylalanine-free; taste-masking