N-trimethyl chitosan chloride-coated liposomes for the oral delivery of curcumin.

The aims of this study were to design the formulation of curcumin (CUR) liposomes coated with N-trimethyl chitosan chloride (TMC) and to evaluate in vitro release characteristics and in vivo pharmacokinetics and bioavailability of TMC-coated CUR liposomes in rats. The structure of synthesized TMC was examined by infrared spectroscopy, with the presence of trimethyl groups, and by proton nuclear magnetic resonance spectroscopy, indicating the high degree of substitution quaternization (65.6%). Liposomes, composed of soybean phosphotidylcholine, cholestrol, and D-α-tocopheryl polyethylene glycol 1000 succinate, were prepared by a thin-film dispersion method. Characteristics of the CUR liposomes, including entrapment efficiency (86.67%), drug-loading efficiency (2.33%), morphology, particle size (221.4 nm for uncoated liposomes and 657.7 nm for TMC-coated liposomes), and zeta potential (-9.63 mV for uncoated liposomes and +15.64 mV for TMC-coated liposomes) were investigated. Uncoated CUR liposomes and TMC-coated CUR liposomes showed a similar in vitro release profile. Nearly 50% of CUR was released from liposomes, whereas 80% of CUR was released from CUR propylene glycol solution. CUR incorporated into TMC-coated liposomes exhibited different pharmacokinetic parameters and enhanced bioavailability (C(max) = 46.13 µg/L, t(1/2) = 12.05 hours, AUC = 416.58 µg/L·h), compared with CUR encapsulated by uncoated liposomes (C(max) = 32.12 µg/L, t(1/2) = 9.79 hours, AUC = 263.77 µg/L·h) and CUR suspension (C(max) = 35.46 µg/L, t(1/2) = 3.85 hours, AUC = 244.77 µg/L·h). In conclusion, oral delivery of coated CUR liposomes is a promising strategy for poorly water-soluble CUR.

Eudragit® S100 coated calcium pectinate microspheres of curcumin for colon targeting.

Currently, colon-specific drug delivery systems have been investigated for drugs that can exert their bioactivities in the colon. In this study, Eudragit® S100 coated calcium pectinate microsphere, a pH-dependent and enzyme-dependent system, as colon-specific delivery carrier for curcumin was investigated. Curcumin-loaded calcium pectinate microspheres were prepared by emulsification-linkage method, and the preparation technology was optimised by uniform experimental design. The morphology of microspheres was observed under scanning electron microscopy. Interactions between drug and polymers were investigated with differential scanning calorimetry (DSC) and X-ray diffraction. In vitro drug release studies were performed in simulated colonic fluid in the presence of Pectinex Ultra SP-L or 1% (w/v) rat caecal content, and the results indicated that the release of curcumin was significantly increased in the presence of 1% (w/v) rat caecal contents. It could be concluded that Eudragit® S100 coated calcium pectinate microsphere was a potential carrier for colon delivery of curcumin.

Design and evaluation of osmotic pump-based controlled release system of Ambroxol Hydrochloride.

The purpose of the present study was to design and evaluate an osmotic pump-based drug delivery system for controlling the release of Ambroxol Hydrochloride (Amb). Citric acid, lactose and polyethylene glycol 6000 (PEG 6000) were employed as osmotic agents. Surelease EC containing polyethylene glycol 400 (PEG 400) controlling the membrane porosity was used as semi-permeable membrane. The formulation of tablet core was optimized by orthogonal design and evaluated by weighted mark method. The influences of the amount of PEG 400 and membrane thickness on Amb release were investigated. The optimal osmotic pump tablet (OPT) was evaluated in different release media and at different stirring rates. The major release power confirmed was osmotic pressure. The release of Amb from OPT was verified at a rate of approximately zero-order, and cumulative release percentage at 12?h was 92.6%. The relative bioavailability of Amb OPT in rabbits relative to the commercial sustained capsule was 109.6%. Our results showed that Amb OPT could be a practical preparation with a good prospect.

Preparation, characterization, pharmacokinetics, and tissue distribution of curcumin nanosuspension with TPGS as stabilizer.

BACKGROUND: CUR is a promising drug candidate based on its good bioactivity, but use of CUR is potentially restricted because of its poor solubility and bioavailability. AIM: The aim of this study was to prepare an aqueous formulation of curcumin nanosuspension (CUR-NS) to improve its solubility and change its in vivo behavior. METHODS: CUR-NS was prepared by high-pressure homogenization method. Drug state in CUR-NS was evaluated by powder X-ray diffraction. Pharmacokinetics and biodistribution of CUR-NS after intravenous administration in rabbits and mice were studied. RESULTS: The solubility and dissolution of CUR in the form of CUR-NS were significantly higher than those of crude CUR. X-ray crystallography diffraction indicated that the crystalline state of CUR in nanosuspension was preserved. Pharmacokinetics and biodistribution results of CUR-NS after intravenous administration in rabbits and mice showed that CUR-NS presented a markedly different pharmacokinetic property as compared to the CUR solution. AUC(0-infinity) of CUR-NS (700.43 +/- 281.53 microg/mL, min) in plasma was approximately 3.8-fold greater than CUR solution (145.42 +/- 9.29 microg/mL min), and the mean residence time (194.57 +/- 32.18 versus 15.88 +/- 3.56 minutes) was 11.2-fold longer. CONCLUSION: Nanosuspension could serve as a promising intravenous drug-delivery system for curcumin.

Curcumin loaded mixed micelles composed of Pluronic P123 and F68: preparation, optimization and in vitro characterization.

In this study, curcumin (Cur) loaded mixed micelles (Cur-PF), composed of Pluronic P123 (P123) and Pluronic F68 (F68), was prepared using the thin-film hydration method and evaluated in vitro. The preparation process was optimized with a central composite design (CCD). The average size of the mixed micelles was 68.2 nm, and the encapsulating efficiency for Cur was 86.93%, and 6.996% for drug-loading. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-PF presented the sustained-release property. The in vitro cytotoxicity assay showed that the IC(50) values on MCF-7 cells for Cur-PF and free Cur in DMSO solution were 5.04 µg/mL and 8.35 µg/mL, while 2.52 µg/mL and 8.27 µg/mL on MCF-7/ADR cells. It could be concluded from the results that P123/F68 mixed micelles might serve as a potential nanocarrier to improve the solubility and biological activity of Cur.

Formulation optimization and bioavailability after oral and nasal administration in rabbits of puerarin-loaded microemulsion.

The main objective of the study was to investigate the efficacy of microemulsion (ME) to facilitate bioavailability of puerarin (PUE) after oral and nasal administration. The pseudo-ternary phase diagrams were constructed to screen the ME components and optimize the ME formulation. The optimized formulation for bioavailability assessment consisted of 20% Tween 80, 20% glycerin, and 1.6% ethyl oleate. The solubility (27.8 mg/mL) of PUE in ME was significantly improved compared to that (4.58 mg/mL) of crude PUE in water. The ME droplets were spherical with a mean particle diameter of 23.4 nm. After nasal (5 mg/kg) and oral (20 mg/kg) administration of a single dose of PUE as ME to fasted rabbits, the absolute bioavailability was 34.58% and 13.54%, respectively. It showed a shorter T(max) (0.75 h) for nasal administration than that (1.0 h) for oral administration of PUE-loaded ME. The C(max) of PUE-loaded ME was 0.55 µg/mL after nasal administration and 0.64 µg/mL after oral administration, respectively. The results showed that nasal administration might be a promising route to enhance the absorption of PUE in the form of ME.

Development of nanosuspension formulation for oral delivery of quercetin.

With the aim to enhance dissolution rate and oral bioavailability of quercetin, a poorly water-soluble drug, quercetin loaded nanosuspension (QT-NS) was fabricated by a tandem of nano-precipitation (NP) and high pressure homogenization (HPH) method. The formulation of nanosuspension was optimized by screening different stabilizers. Characterization of the original QT powder and QT-NS was carried out by transmission electron microscopy and scanning electron microscopy, X-ray diffraction (XRD) and dissolution tests. QT-NS presented a sphere-like shape under transmission electron microscopy with an average diameter of 393.5 nm and the zeta potential of -35.75 mV. XRD study suggested that QT was maintained in the state of crystalline during the fabrication process. The solubility of QT in nanosuspension was about 70-fold that of crude QT, and the dissolution of QT from QT-NS was increased as compared to that of the original QT powder. In plasma, QT-NS exhibited a significant reduction of clearance rate (2 +/- 0.1 mL/min vs. 15 +/- 4 mL/min) and increase of AUC(0-infinity), (53995 +/- 4126 microg/mL x min versus 3470 +/- 110.1 microg/mL x min) compared with the control suspension. Our results showed that the developed nanosuspension formulation had a great potential as a possible formulation of the poorly water-soluble QT to enhance the bioavailability.