Abstract
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). 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. 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. LST-18 succeeded in increasing oral FXD bioavailability by 62% and reducing Tmax to 2.16 h.
Highlights
The concept of liquisolid powder design According to Spireas and Bolton hypothesis,[17] when the liquid medication (FXD in Propylene glycol (PG) or in Cremophor® EL (CR)) is added to a porous carrier material, like Avicel® PH 102, both absorption and adsorption take place
It is clear that the characteristic peak of Fexofenadine hydrochloride (FXD) is maintained in the physical mixture
The splitting of the characteristic peak of the drug into two peaks and the decrease in the intensities of the peaks, in the Fourier Transform Infra-Red (FT-IR) spectrum of the liquisolid system could indicate the presence of drug – excipient interaction
Summary
The dissolution rate is considered as the rate-determining step for absorption of poorly water-soluble drugs formulated in orally administered solid dosage forms.Various techniques were explored to enhance the solubility and dissolution properties of such drugs including; micronization of drugs,[1] development of various nanobased systems,[2] use of solid dispersions,[3] addition of surfactants and co-surfactants,[4] changing the drug to an amorphous state,[5] development of inclusion complexes with cyclodextrins,[6] use of pro-drug and drug derivatization,[7] dispersion in a porous matrix,[8] loading on carriers having high surface area,[9] development of orodispersible tablets via incorporation of superdisintegrants or sublimable agents.[10]. The liquisolid compacts are regarded as acceptably flowing and compressible powdered forms of a liquid medication The latter include liquid lipophilic drugs or solid water-insoluble drugs dissolved in suitable watermiscible non-volatile solvents. The drug is held within the powder substrate in solution or in a solubilized, almost molecularly dispersed state.[14] due to their significantly increased wetting properties and surface area of drug available for dissolution, liquisolid compacts of water-insoluble drugs are expected to enhance the drug release characteristics and to improve oral bioavailability.[15,16] The flowability as well as the compressibility of the investigated liquisolid compacts were addressed simultaneously according to the „„new formulation mathematical model of liquisolid systems” developed by Spireas and Bolton.[17] According to this model, the appropriate quantities of the carrier and coating materials for each liquid vehicle could be calculated following the estimation of certain fundamental powder properties; the flowable liquid retention potential (Φ-value) and the compressible liquid retention potential (Ψ-number).[18]
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