Phyllanthin, a poorly water-soluble herbal active component from Phyllanthus amarus, exhibited a low oral bioavailability. This study aims at formulating self-microemulsifying drug delivery systems (SMEDDS) containing phyllanthin and evaluating their in-vitro and in-vivo performances. Excipient screening was carried out to select oil, surfactant and co-surfactant. Formulation development was based on pseudo-ternary phase diagrams and characteristics of resultant microemulsions. Influences of dilution, pH of media and phyllanthin content on droplet size of the resultant emulsions were studied. The optimized phyllanthin-loaded SMEDDS formulation (phy-SMEDDS) and the resultant microemulsions were characterized by viscosity, self-emulsification performance, stability, morphology, droplet size, polydispersity index and zeta potential. In-vitro dissolution and oral bioavailability in rats of phy-SMEDDS were studied and compared with those of plain phyllanthin. Phy-SMEDDS consisted of phyllanthin/Capryol 90/Cremophor RH 40/Transcutol P (1.38:39.45:44.38:14.79) in % w/w. Phy-SMEDDS could be emulsified completely within 6 min and formed fine microemulsions, with average droplet range of 27-42 nm. Phy-SMEDDS was robust to dilution and pH of dilution media while the resultant emulsion showed no phase separation or drug precipitation after 8 h dilution. The release of phyllanthin from phy-SMEDDS capsule was significantly faster than that of plain phyllanthin capsule irrespective of pH of dissolution media. Phy-SMEDDS was found to be stable for at least 6 months under accelerated condition. Oral absorption of phyllanthin in rats was significantly enhanced by SMEDDS as compared with plain phyllanthin. Our study indicated that SMEDDS for oral delivery of phyllanthin could be an option to enhance its bioavailability.

Phyllanthin is a major bioactive lignan component of Phyllanthus amarus, with several known biological activities. This study dealt with the isolation and physicochemical characterization of phyllanthin. Phyllanthin was isolated from P. amarus leaves by column chromatography and purified by recrystallization to obtain phyllanthin crystals with a purity of more than 98%. UV, IR, MS, ¹H NMR and ¹³C NMR spectra were employed to identify phyllanthin. The physicochemical properties of phyllanthin were characterized using differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction, pH-solubility, ionization property and lipophilicity. The results indicated that phyllanthin crystals had the melting point and melting enthalpy range of 96.67–97.03 °C and 109.61–116.34 J/g, respectively. Three kinds of phyllanthin crystals, recrystallized by petroleum ether, absolute ethanol and 25% ethanol solution, showed only one polymorph and no polymorphic impurity. Phyllanthin in a solid state was found to undergo significant thermal decomposition above 200 °C. The compound demonstrated good stability in aqueous solution over a pH range of 1.07–10.02 for at least 4 h. The solubility of phyllanthin appeared to be pH-independent of pH range from 1.07 to 10.26. Ionization property studied by absorbance spectroscopy method was in agreement with the result of pH-solubility study, showing that phyllanthin has no pK_a over a pH range of 1.12–10.02. The log P_ow value of phyllanthin was found to be 3.30 ± 0.05 at pH 7.48, suggesting that phyllanthin may have good permeability through biological membranes. The findings could be useful tools for the development of stable and bioavailable oral dosage forms of phyllanthin.

Objective: Exemestane is an anti-breast cancer drug, possesses low water solubility and low permeability. This work aimed at the cause-effect relations and optimization of exemestane-loaded nanostructured lipid carriers (EXE-NLCs) for oral delivery.Methods: Excipient screening was based on exemestane solubilities and the emulsification efficiency of surfactants. A D-optimal design based on three independent variables was applied to evaluate the cause-effect relations and optimise EXE-NLCs formulation. The particle size (PS), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL) were investigated with respect to three independent variables including liquid lipid to total lipid ratio (X1), surfactant concentration (X2), total lipid concentration (X3).Results: EXE-NLCs were prepared by a hot sonication method employing Labrafac CC and Compritol 888ATO as liquid and solid lipids, respectively, and Cremophor RH40 as a surfactant and Lutrol E-400 as a co-surfactant. All investigated factors: liquid lipid to total lipid ratio, surfactant concentration and total lipid concentration showed significant influences on physicochemical characteristics of EXE-NLCs. The optimal EXE-NLC formulation was composed of liquid lipid to total lipid ratio (X1) of 24 % (w/w), surfactant concentration (X2) of 4 % (w/v) and total lipid concentration (X3) of 4 % (w/v). The PS, PDI, EE and DL of the optimized EXE-NLCs were found to be 41.787 nm; 0.11; 97.605 % and 1.935 %, respectively. The optimized formulation was experimentally examined which demonstrated a good agreement between experimental and predicted values.Conclusion: The cause-effect relations and optimization of EXE-NLCs were investigated and reported for the first time. EXE-NLCs formulation was successfully optimized using D-optimal design and merits further study.

Millettia pulchra is traditionally used for treating diseases, including joint pain, fever, anemia, and allergies. It is also a potential resource of natural flavonoid derivatives, which represents major constituents of this plant. This study aimed to isolate the major compounds from M. pulchra radix, develop and validate the HPLC-PDA method to determine their contents, and optimize its extraction. Four major flavonoid derivatives (karanjin, lanceolatin B, 2”,2”-dimethylpyrano-[5″,6″:7,8]-flavone, and pongamol) were isolated using silica gel column chromatography, crystallization techniques in large amounts with high purities (>95%). A simple, accurate high-performance liquid chromatography–photodiode array (HPLC–PDA) detection method has been developed and validated with significantly statistical impacts according to International Conference on Harmonization (ICH) guidelines. The Response Surface Methodology (RSM), Artificial Neural Network (ANN) models were employed to predictive performance and optimization of the extraction process. The optimized conditions for the extraction of major flavonoids were: extraction time (twice), solvent/material ratio (9.5), and ethanol concentration (72.5%). Our research suggests an effective method, which will be helpful for quality control in the pharmaceutical development of this species.

Curcuma aromatica, the herbal medicine belongs to Zingiberaceae family, is well known for anti-tumor activity through multiple pathways and a potential candidate for complementary medicine in cancer treatment. The aims of this study were to distinguish between Curcuma species based on polymorphisms of the nucleotide sequence of chloroplast DNA (cpDNA) and preliminarily analyze their potential-anticancer compounds. Totally six samples supposed C. aromatica growing in An Giang province, Vietnam were collected. The contents of curcumin, curdione, and germacrone in the six samples were analyzed and compared by using the high-performance liquid chromatography (HPLC) method. All specimens were identified according to their trnSfMintergenic spacer sequences by Sanger sequencing. Among the six samples, three were determined as C. aromatica, two were C. longa, and one was C. zedoaria. Curcumin, curdione, and germacrone, known as anticancer compounds, were simultaneously found in sample NT3 that identified as C. aromatica by Sanger sequencing. The obtained results revealed a potential herbal candidate for complementary and alternative medicine.