curcumin and hydroxypropylmethylcellulose-acetate-succinate

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.

Topics: Chemistry, Pharmaceutical; Curcumin; Drug Stability; Methylcellulose; Polymers; Solubility

An advanced oral drug delivery system that can effectively deliver drugs with poor oral bioavailability is strongly desirable. Herein, a multifunctional nano-in-micro structured composite is developed by encapsulation of the mucoadhesive poly(methyl vinyl ether-co-maleic acid) modified halloysite nanotubes (HNTs) with the pH-responsive hydroxypropyl methylcellulose acetate succinate by the microfluidics to control the drug release, increase cell-particle interaction, and improve drug absorption. The microparticles show spherical shape, homogeneous particle size distribution (58 ± 1 µm), and pH-responsive dissolution behavior at pH > 6, and they prevent the premature release of curcumin in simulated pH conditions of the stomach and immediately release the curcumin in simulated pH conditions of the small intestine. The surface modification of HNT with mucoadhesive poly(methyl vinyl ether-co-maleic acid) significantly enhances its interactions with the intestinal Caco-2/HT29-MTX cells and the mouse small intestines, and increases the permeability of curcumin across the co-cultured Caco-2/HT29-MTX cell monolayers by about 13 times compared to the free curcumin. Therefore, the developed multifunctional nanotube-mucoadhesive poly(methyl vinyl ether-co-maleic acid)@hydroxypropyl methylcellulose acetate succinate composite is a promising oral drug delivery system for drugs with poor oral bioavailability.

Topics: Administration, Oral; Animals; Caco-2 Cells; Cell Proliferation; Cell Survival; Curcumin; Drug Carriers; Drug Liberation; HT29 Cells; Humans; Hydrogen-Ion Concentration; Intestine, Small; Maleates; Methyl Ethers; Methylcellulose; Mice; Nanotubes; Particle Size; Permeability; Polyvinyls

The purpose of the present study was to formulate polymeric self-emulsifying curcumin nanocapsules with high encapsulation efficiency, good emulsification ability, and optimal globule size for localized targeting in the colon. Formulations were prepared using modified quasiemulsion solvent diffusion method. Concentration of formulation variables, namely, X1 (oil), X2 (polymeric emulsifier), and X3 (adsorbent), was optimized by design of experiments using Box-Behnken design, for its impact on mean globule size (Y1) and encapsulation efficiency (Y2) of the formulation. Polymeric nanocapsules with an average diameter of 100-180 nm and an encapsulation efficiency of 64.85±0.12% were obtained. In vitro studies revealed that formulations released the drug after 5 h lag time corresponding to the time to reach the colonic region. Pronounced localized action was inferred from the plasma concentration profile (C max 200 ng/mL) that depicts limited systemic absorption. Roentgenography study confirms the localized presence of carrier (0-2 h in upper GIT; 2-4 h in small intestine; and 4-24 h in the lower intestine). Optimized formulation showed significantly higher cytotoxicity (IC50 value 20.32 μM) in HT 29 colonic cancer cell line. The present study demonstrates systematic development of polymeric self-emulsifying nanocapsule formulation of curcumin for localized targeting in colon.

Topics: Animals; Calorimetry, Differential Scanning; Cell Survival; Chemistry, Pharmaceutical; Curcumin; Drug Delivery Systems; Emulsifying Agents; Gastrointestinal Tract; Guinea Pigs; HT29 Cells; Humans; Methylcellulose; Nanocapsules; Polymers; Radiography; Regression Analysis; Solubility; X-Ray Diffraction