Improved Bioavailability of Poorly Water-Soluble Drug Curcumin in Cellulose Acetate Solid Dispersion

Abstract

Abstract. Curcumin (Cur), one of the most widely used natural active constituents with a great variety of beneficial biological and pharmacological activities, is a practically water-insoluble substance with a short biologic half-life. The aim of this study was to develop a sustained-release solid dispersion by employing water-insoluble carrier cellulose acetate for solubility enhancement, release control, and oral bioavailability improvement of Cur. Solid dispersions were characterized by solubility, in vitro drug release, Fourier transform infrared spectroscopy, X-ray diffractometry, and differential scanning calorimetry studies. The in vivo performance was assessed by a pharmacokinetic study. Solid-state characterization techniques revealed the amorphous nature of Cur in solid dispersions. Solubility/ dissolution of Cur was enhanced in the formulations in comparison with pure drug. Sustained-release profiles of Cur from the solid dispersions were ideally controlled in vitro up to 12 h. The optimized formulation provided an improved pharmacokinetic parameter (C max =187.03 ng/ml, t max =1.95 h) in rats as compared with pure drug (C max =87.06 ng/ml, t max =0.66 h). The information from this study suggests that the developed solid dispersions successfully enhanced the solubility and sustained release of poorly water-soluble drug Cur, thus improving its oral bioavailability effectively.

Functionalized Polymers from Lignocellulosic Biomass: State of the Art

“…Given the dynamic development and implementation of nanomaterials, CA has been successfully employed as a precursor for matrices, nanoparticles and nanofibers. In the year 2012 alone, CA was used to prepare membranes for nanofiltration [31][32][33][34][35][36][37][38][39][40][41][42], organoclay nanocomposites [43][44][45], antimicrobial wound dressing [46], bone regeneration material [47], biosensors [48], bioreactors [49], polymer electrolyte [50,51], energetic materials (composite explosives and propellants) [52], insulating [53] and fireproofing materials [54], and novel drug delivery systems [49,55].…”

Microparticles Containing Curcumin Solid Dispersion: Stability, Bioavailability and Anti-Inflammatory Activity

“…However, curcumin low solubility in aqueous solutions (7,8), instability in alkaline pH and short half-life lead to low oral bioavailability and therapeutic limitations (8)(9)(10)(11)(12)(13)(14)(15)(16). Curcumin solubility is a determining factor for its bioavailability when administered orally (17) and huge scientific work has been devoted to overcome this limitation (8,(18)(19)(20)(21)(22).…”

“…Despite their high solubility enhancement, the drug load was very low in both cases, limiting their use in solid oral dosage forms (33). Cellulose acetate-mannitol dispersion (22) was capable of increasing curcumin solubility 4-fold but in an aqueous media containing 15% ethanol. Cyclodextrins inclusion complexes were also evaluated and resulted in about 202-fold curcumin solubility improvement (10) and faster dissolution rates.…”

“…Cyclodextrins inclusion complexes were also evaluated and resulted in about 202-fold curcumin solubility improvement (10) and faster dissolution rates. However, none of these papers addressed the stability of curcumin solid dispersions, which is an important factor for pharmaceutical purposes (22,25,28) since recrystallization may decrease drug solubility with time (27). Moreover, SD physical-chemical characterisation and stability are rarely addressed along with in vitro and in vivo tests in solid dispersion studies (34).…”

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“…Deposition of drug on the surface of an inert carrier leads to a reduction in the particle size of the drug, thereby providing a faster dissolution rate. Various hydrophilic materials with high surface area can be utilized for deposition of the drug on their surfaces 11 . Surface modification and solid-dispersion formulations using hydrophilic excipients can significantly alter the dissolution behavior of hydrophobic drug materials.…”