Design of Turmeric Rhizome Extract Nano-Formula for Delivery to Cancer Cells.

Novel turmeric rhizome extract nanoparticles (TE-NPs) were developed from fractions of dried turmeric (Curcuma longa Linn.) rhizome. Phytochemical studies, by using HPLC and TLC, of the fractions obtained from ethanol extraction and solvent-solvent extraction showed that turmeric rhizome ethanol extract (EV) and chloroform fraction (CF) were composed mainly of three curcuminoids and turmeric oil. Hexane fraction (HE) was composed mainly of turmeric oil while ethyl acetate fraction (EA) was composed mainly of three curcuminoids. The optimal TE-NPs formulation with particle size of 159.6 ± 1.7 nm and curcumin content of 357.48 ± 8.39 µM was successfully developed from 47-run D-optimal mixture-process variables experimental design. Three regression models of z-average, d50, and d90 could be developed with a reasonable accuracy of prediction (predicted r2 values were in the range of 0.9120-0.9992). An in vitro cytotoxicity study using MTT assay demonstrated that the optimal TE-NPs remarkably exhibited the higher cytotoxic effect on human hepatoma cells, HepG2, when compared with free curcumin. This study is the first to report nanoparticles prepared from turmeric rhizome extract and their cytotoxic activity to hepatic cancer cells compared with pure curcumin. These nanoparticles might serve as a potential delivery system for cancer therapy.

Design and optimization of resveratrol-loaded porous calcium silicate powders for dissolution and photostability enhancement.

In this study, resveratrol (RVT) was loaded onto porous calcium silicate (PCS) powders to improve its dissolution and photostability properties. The effects of RVT/PCS powders that included varying amounts of low-methoxyl pectin (LMP), ethyl acetate (EA) and PCS on drug loading capacity, encapsulation efficiency and drug dissolution at 5-min intervals (Q5) were investigated using a Box-Behnken design. The experimental results demonstrated that the EA and PCS amounts significantly influenced drug loading capacity. Encapsulation efficiency was affected by EA amount, whereas the amount of PCS had a significant effect on Q5. Empirical experiments demonstrated the reliability of mathematical models. A design space was established based on the criteria set for maximizing each response of the RVT/PCS powders. An optimized formulation containing 2.6% w/w LMP, 19% w/w EA and 13% w/w PCS prepared within the design space satisfied all criteria. The dissolution and photostability of RVT in the RVT/PCS powders were significantly improved. Further, the bulk density of the PCS powders in RVT/PCS was increased by LMP. The Box-Behnken design used in this study provided an improved understanding of the effects of formulation factors on RVT/PCS powder characteristics as well as the optimization of RVT/PCS powder formulations with the desired properties.

Use of Risk Assessment and Plackett-Burman Design for Developing Resveratrol Spray-Dried Emulsions: a Quality-by-Design Approach.

In this study, the resveratrol spray-dried emulsions were developed using a quality-by-design approach. Further, the product and process factors that affected the quality of the spray-dried emulsions were analyzed and illustrated using an Ishikawa diagram. The product and process risks were prioritized using a risk-ranking system. The low methoxyl pectin (LMP) amount, caprylic/capric glyceride (CCG) amount, homogenization time, homogenization speed, inlet temperature, pump speed, drying airspeed, and de-blocking speed were observed to be the eight highest risk factors. Further, the criticality of these eight factors on the responses was determined using the Plackett-Burman design. Increasing the LMP amount increased the particle size, whereas increasing the CCG amount enhanced the drug-loading capacity and drug dissolution at 5-min intervals (Q5) and decreased the moisture content. Q5 was positively affected by the homogenization speed and pump speed; however, it was negatively affected by the LMP amount. The spraying efficiency was affected by the pump speed and the LMP amount. Further, the risk level of the homogenization time, inlet temperature, drying airspeed, and de-blocking speed were reduced. However, the LMP amount, CCG amount, homogenization speed, and pump speed were observed to remain at high risk and require further investigation. The risk assessment and Plackett-Burman design mitigated the risks and identified the critical factors that affected the quality of the resveratrol spray-dried emulsions and the spray-drying process.

Effect of high-pressure homogenization on stability of emulsions containing zein and pectin.

The aim of this study was to investigate the effect of high-pressure homogenization on the droplet size and physical stability of different formulations of pectin-zein stabilized rice bran oil emulsions. The obtained emulsions, both before and after passing through high-pressure homogenizer, were subjected to stability test under environmental stress conditions, that is, temperature cycling at 4 °C/40 °C for 6 cycles and centrifugal test at 3000 rpm for 10 min. Applying high-pressure homogenization after mechanical homogenization caused only a small additional decrease in emulsion droplet size. The droplet size of emulsions was influenced by the type of pectin used; emulsions using high methoxy pectin (HMP) were smaller than that using low methoxy pectin (LMP). This is due to a greater emulsifying property of HMP than LMP. The emulsions stabilized by HMP-zein showed good physical stability with lower percent creaming index than those using LMP, both before and after passing through high-pressure homogenizer. The stability of emulsions after passing through high-pressure homogenizer was slightly higher when using higher zein concentration, resulting from stronger pectin-zein complexes that could rearrange and adsorb onto the emulsion droplets.

Effect of source variation on drug release from HPMC tablets: linear regression modeling for prediction of drug release.

The aim of this study was to investigate the effect of source variation of hydroxypropyl methylcellulose (HPMC) raw material on prediction of drug release from HPMC matrix tablets. To achieve this objective, the flow ability (i.e., angle of repose and Carr's compressibility index) and apparent viscosity of HPMC from 3 sources was investigated to differentiate HPMC source variation. The physicochemical properties of drug and manufacturing process were also incorporated to develop the linear regression model for prediction of drug release. Specifically, the in vitro release of 18 formulations was determined according to a 2 × 3 × 3 full factorial design. Further regression analysis provided a quantitative relationship between the response and the studied independent variables. It was found that either apparent viscosity or Carr's compressibility index of HPMC powders combining with solubility and molecular weight of drug had significant impact on the release behavior of drug. The increased drug release was observed when a greater in drug solubility and a decrease in the molecular weight of drug were applied. Most importantly, this study has shown that the HPMC having low viscosity or high compressibility index resulted in an increase of drug release, especially in the case of poorly soluble drugs.

Wax-incorporated emulsion gel beads of calcium pectinate for intragastric floating drug delivery.

The purpose of this study was to prepare wax-incorporated pectin-based emulsion gel beads using a modified emulsion-gelation method. The waxes in pectin-olive oil mixtures containing a model drug, metronidazole, were hot-melted, homogenized and then extruded into calcium chloride solution. The beads formed were separated, washed with distilled water and dried for 12 h. The influence of various types and amounts of wax on floating and drug release behavior of emulsion gel beads of calcium pectinate was investigated. The drug-loaded gel beads were found to float on simulated gastric fluid if the sufficient amount of oil was used. Incorporation of wax into the emulsion gel beads affected the drug release. Water-soluble wax (i.e. polyethylene glycol) increased the drug release while other water-insoluble waxes (i.e. glyceryl monostearate, stearyl alcohol, carnauba wax, spermaceti wax and white wax) significantly retarded the drug release. Different waxes had a slight effect on the drug release. However, the increased amount of incorporated wax in the formulations significantly sustained the drug release while the beads remained floating. The results suggest that wax-incorporated emulsion gel beads could be used as a carrier for intragastric floating drug delivery.