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Glaucocalyxin A (GLA), is a diterpenoid extracted from Hara and has been studied for decades for its diverse bioactivities. However, GLA presents poor solubility in water and low bioavailability through oral administration which has hindered its application in the clinic. So in this study, we prepared the inclusion complex of GLA in SBE-β-CD by ultrasound method and evaluated its antitumor effect and cytotoxic effect on cancer cells. The production of GLA-SBE-β-CD inclusion complex was optimized using Box-Behnken design. The inhibitory effects of GLA and GLA-SBE-β-CD were investigated on the Hela, A549, HepG2, and SiHa cells in vitro by MTT staining assay. Pharmacokinetic studies were conducted on Sprague-Dawley mice via caudal injection to study the distribution, metabolism, and elimination of GLA-SBE-β-CD in vivo. Tumor-bearing nude mice were taken as the model and adopted to evaluate the inhibitory rate of GLA and GLA-SBE-β-CD on the transplanted tumor. A series of physical characterization results confirmed the fact that GLA-SBE-β-CD inclusion complex was successfully prepared. A production of 87.28% was achieved based on the Box-Behnken design. In the cancer cell inhibition studies, GLA and GLA-SBE-β-CD exhibited apparent concentration-dependent inhibitory actions on four kinds of tumor cells and better inhibition was achieved in GLA-SBE-β-CD group. The pharmacokinetic results showed that the duration of GLA in blood was prolonged and enhanced bioavailability was achieved. GLA and GLA-SBE-β-CD both showed an effective inhibition on the transplanted tumor growth, while the anti-tumor effect of GLA-SBE-β-CD (inhibitory rate of 45.80%) was significantly stronger than that of GLA (30.76%) based on the change of tumor weight and tumor volume. [ABSTRACT FROM AUTHOR]

The present research indicated that a new self-microemulsifying drug delivery systems (SMEDDS) were used to reduce the food effect of poorly water-soluble drug cinacalcet and enhance the bioavailability in beagle dogs by oral gavage. Ethyl oleate, OP-10, and PEG-200 was selected as the oil phase, surfactant and co-surfactant of cinacalcet-SMEDDS by the solubility and phase diagram studies. Central Composite Design-Response Surface Methodology was used to determine the ratio of surfactant and co-surfactant, the amount of oil for optimizing the SMEDDS formation. The prepared formulations were further characterized by the droplet size, self-microemulsifying time, zeta potential, polydispersity index (PDI), and robustness to dilution. The in vitro release profile of cinacalcet-SMEDDS was determined in four different release medium and in fasted state and fed state of simulated gastrointestinal fluid. Cinaclcet-SMEDDS were implemented under fed and fasted state in dogs and product REGPARA® was used as a comparison to the prepared formulation in the pharmacokinetics. The result showed the components of SMEDDS, the amount of oil, the ratio of surfactant, and co-surfactant was optimized using solubility, pseudo-ternary phase diagram studies, and response surface methodology. In vitro drug release studies indicated that the cinacalcet-SMEDDS eliminated the effect of pH variability in release medium and variational gastroenteric environments with improved drug release performance. Pharmacokinetic studies revealed that the profiles of cinacalcet-SMEDDS were similar both in the fasted and fed state compared with commercial product, indicating the formulation significantly promoted the absorption, enhanced bioavailability and had no food effect essentially. It is concluded that poorly water-soluble drug cinacalcet was improved in the solubility and bioavailability by using a successful oral dosage form the SMEDDS, and eliminated food effect as well. [ABSTRACT FROM AUTHOR]

The purpose of this work was to develop self-nanomulsifying drug delivery systems (SNEDDS) in sustained-release pellets of ziprasidone to enhance the oral bioavailability and overcome the food effect of ziprasidone. Preformulation studies including screening of excipients for solubility and pseudo-ternary phase diagrams suggested the suitability of Capmul MCM as oil phase, Labrasol as surfactant, and PEG 400 as co-surfactant for preparation of self-nanoemulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the pseudo-ternary phase diagrams. The prepared ziprasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized ziprasidone-SNEDDS were used to prepare ziprasidone-SNEDDS sustained-release pellets via extrusion-spheronization method. The pellets were characterized for SEM, particle size, droplet size distribution and zeta potential.In vitrodrug release studies indicated the ziprsidone-SNEDDS sustained-release pellets showed sustained release profiles with 90% released within 10 h. The ziprsidone-SNEDDS sustained-release pellets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation of Zeldox as a control. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolonged actions and enhanced bioavailability with no food effect was achieved simultaneously in ziprsidone-SNEDDS sustained-release pellets compared with Zeldox in fed state. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this work was to develop ziprasidone-phospholipid complex ( ZIP- PLC) in sustained-release pellets to enhance the oral bioavailability and overcome the food effect of ziprasidone. Methods Ziprasidone-phospholipid complex was formulated by solvent-evaporation method. The complexes were characterized by Fourier transform infrared spectroscopy ( FTIR), scanning electron microscopy ( SEM), differential scanning calorimetry ( DSC), powder X-ray diffraction ( PXRD) and solubility testing. The optimized ZIP- PLC was used to prepare ZIP- PLC sustained-release pellets via extrusion-spheronization method. The pellets were characterized by in vitro drug-release studies and administered to fasted and fed beagle dogs, and their pharmacokinetics were compared with commercial formulation Zeldox capsule as a control. Key findings The results of FTIR, SEM, DSC and PXRD studies confirmed the formation of phospholipid complex. Solubility studies showed there was a higher solubility in water for ZIP- PLC than monohydrate ziprasidoe. The in vitro release rate of ziprasidone from the ZIP- PLC sustained-release pellet exhibited controlled-release characteristics with over 95% total release in 12 h. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolong actions, and no food effect was achieved simultaneously in ZIP- PLC sustained-release pellet compared with Zeldox capsule. Conclusions The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment. [ABSTRACT FROM AUTHOR]

Docetaxel (DTX), as a first-line anti-tumor drug, has been studied for decades for its diverse bioactivities. However, DTX presents poor solubility in water, low bioavailability and serious toxic side effects which has hindered its application in the clinic. To address these problems, docetaxel-sulfobutyl ether-β-cyclodextrin inclusion complex (DTX-SBE-β-CD) was prepared successfully by saturated aqueous solution method. Sulfobutyl ether β-cyclodetrin (SBE-β-CD) is used as delivery material. For this study, the inclusion complex of docetaxel with sulfobutyl ether β-cyclodetrin (DTX-SBE-β-CD) was prepared and optimized its properties to enhance the cytotoxicity of cancer cells. A large number of physical characterization results showed that DTX-SBE-β-CD inclusion complex was successfully prepared by saturated aqueous solution method. DTX-SBE-β-CD inclusion complex was optimized by Central Composite Design. DTX-SBE-β-CD had an inhibitory effect on the in vitro determination of MCF-7 and HepG2 cells by MTT assay. Pharmacokinetic studies were carried out on male Sprague–Dawley rats by tail injection, including the distribution, metabolism and elimination of DTX-SBE-β-CD in vivo. In the experimental study of inhibition of cancer cells, DTX and DTX-SBE-β-CD showed apparent concentration-dependent inhibitory actions on tumor cells and the inhibition of DTX-SBE-β-CD group was more obvious. [ABSTRACT FROM AUTHOR]