Design and preparation of controlled floating gastroretentive delivery systems for enhanced fexofenadine hydrochloride oral bioavailability

Purpose: To design and prepare effervescent floating gastroretentive tablets for controlledfexofenadine hydrochloride (HCl) release and enhanced oral bioavailability.Method: Various tablet formulations of the drug were prepared by direct compression. A systematic approach in the design of the formulations was adopted, where, first, formulations consisting of single polymers with a high polymer : sodium bicarbonate ratio were investigated for its physicochemical properties (in-vitro floating behaviour, drug release profile, etc). Next, improvement of tablets’ properties was achieved by decreasing polymer : sodium bicarbonate ratio. Subsequently, a final optimization step involved blending polymers at different polymer : polymer ratios. The formulations were evaluated in vitro and in vivo in albino rabbitsResults: The formulation consisting of hydroxypropyl methylcellulose K15M/hydroxypropylmethyl cellulose K100LV at 1 : 2 ratio (F8) showed good floating properties (14 s floating lag time) with nearly zero order controlled drug release for 24 h (R2 = 0.9876). In-vivo bioavailability studies of F8 in albino rabbits showed a significant increase in area under the curve (AUC, 134 %, p < 0.05) and hence an improvement in its oral bioavailability, compared to a commercial conventional product.Conclusion: The good quality of the effervescent floating gastroretentive tablets of fexofenadine HCl developed is an indication that the approach used is suitable for the formulation of the drug for controlled drug release and enhanced oral bioavailabiliy.Keywords: Effervescent, Floating, Gastroretentive, Fexofenadine, Bioavailabilit

Spray-dried co-amorphous Tadalafil ternary mixtures: a promising platform towards the enhancement of solubility and bioavailability

Tadalafil (Tad) is a poorly water-soluble drug (BCS class II) that is used for the treatment of erectile dysfunction. An enhancement of aqueous solubility is vital to accelerate its onset of action and subsequently enhance its therapeutic effect. Binary and ternary mixtures of Tad with different amino acids (histidine, valine, alanine or arginine) and other excipients (mannitol and SLS) were prepared and then spray dried. The solubilizing efficiency and physicochemical characterization of all spray dried mixtures of Tad were studied. The optimum formulation was investigated in male rats to determine the onset of erection and the pharmacokinetic parameters of Tad. In general terms, the drug solubility of spray-dried formulae was enhanced compared to the crystalline form of the drug as a result of the formation of co-amorphous structures. The final result revealed that the Tad/alanine/mannitol spray-dried mixture (F10) showed the highest solubility and an improvement in its physicochemical characteristics. Moreover, F10 showed a significantly faster erection in rats with an improvement in Tad pharmacokinetic parameters when compared to the crystalline drug. Thus, F10 is selected as a promising formulation that successfully enhanced the bioavailability and the therapeutic efficacy of Tad

Spray-dried co-amorphous Tadalafil ternary mixtures: a promising platform towards the enhancement of solubility and bioavailability

Abstract Tadalafil (Tad) is a poorly water-soluble drug (BCS class II) that is used for the treatment of erectile dysfunction. An enhancement of aqueous solubility is vital to accelerate its onset of action and subsequently enhance its therapeutic effect. Binary and ternary mixtures of Tad with different amino acids (histidine, valine, alanine or arginine) and other excipients (mannitol and SLS) were prepared and then spray dried. The solubilizing efficiency and physicochemical characterization of all spray dried mixtures of Tad were studied. The optimum formulation was investigated in male rats to determine the onset of erection and the pharmacokinetic parameters of Tad. In general terms, the drug solubility of spray-dried formulae was enhanced compared to the crystalline form of the drug as a result of the formation of co-amorphous structures. The final result revealed that the Tad/alanine/mannitol spray-dried mixture (F10) showed the highest solubility and an improvement in its physicochemical characteristics. Moreover, F10 showed a significantly faster erection in rats with an improvement in Tad pharmacokinetic parameters when compared to the crystalline drug. Thus, F10 is selected as a promising formulation that successfully enhanced the bioavailability and the therapeutic efficacy of Tad

Karakterizacija ternarnih kompleksa meloksikam-HPbCD i PVP ili L-arginina pripravljenih metodom sušenja sprejom

Ternary complexes of meloxicam (ME) (a poorly water soluble anti-inflammatory drug) with hydroxypropyl-b-cyclodextrin (HPbCD) and either a hydrophilic polymer, namely, polyvinyl pyrrolidone (PVP) or a basic amino acid such as L-arginine, were prepared by the spray-drying technique. The solubilizing efficiency, physical properties and dissolution behaviour of each ternary systems of ME-HPCD with either PVP or L-arginine were compared with those of the corresponding binary system of ME-HPCD. Tablets compressed from ternary system of ME-HPCD-L-argininewere compared with plain and commercial tablets. Phase solubility experiments suggested the formation of inclusion complex of AL type. Ternary system of ME-HPbCD-L-arginine exhibited a stability constant 30.3 times higher than the binary system of ME-HPbCD, while the ternary system of ME-HPbCD-PVP increased the stability constant 2.2 times only. The prepared complexes were characterized by scanning electron microscopy, differential scanning calorimetry and infra red spectroscopy. Ternary solid complexes indicated the presence of strong interactions between the components. The dissolution behaviour of ME from different ternary complexes was higher than its dissolution from the binary system. Tablets compressed from ternary complexes of ME-HPbCD-L-arginine highly improved drug release compared to plain and commercial tablets.Ternarni kompleksi meloksikama (ME) (slabo vodotopljivi protuupalni lijek) s hidroksipropil-b-ciklodekstrinom (HPbCD) i/ili hidrofilnim polimerom polivinil pirolidonom (PVP) ili bazičnom aminokiselinom poput L-arginina, pripravljeni su metodom sušenja sprejom. Uspoređivan je utjecaj topljivosti, fizikalna svojstva i oslobađanje svakog ternarnog sustava ME-HPCD s PVP ili L-argininom s odgovarajućim binarnim sustavom ME-HPCD. Tablete priređene iz ternarnog sustava ME-HPCD-L-arginin uspoređene su s jednostavnim i komercijalno dostupnim tabletama. Pokusi topljivosti ukazuju na to da se stvara inkluzijski kompleks AL tipa. Ternarni sustav ME-HPbCD-L-arginin imao je konstantu stabilnosti 30,3 puta veću nego binarni sustav ME-HPbCD, dok je ternarni sustav ME-HPbCD-PVP imao tu konstantu uvećanu za samo 2,2 puta. Pripravljeni kompleksi karakterizirani su pomoću pretražne elektronske mikroskopije, diferencijalne pretražne kalorimetrije i infracrvene spektroskopije. Ternarni čvrsti kompleksi ukazali su na prisutnost snažnih interakcija između komponenata. Oslobađanje ME iz različitih ternarnih kompleksa bilo je veće nego iz binarnih sustava. Tablete komprimirane iz ternarnog kompleksa ME-HPbCD-L-arginin imaju značajno poboljšano oslobađanje ljekovite tvari u usporedbi s jednostavnim i komercijalno dostupnim tabletama