PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2021
·
IF 3.133
Kang Sha,Qianfang Ma,Hanitrarimalala Veroniaina,Xiaole Qi,Jiayi Qin,Zhenghong Wu
Solidification of self-microemulsifying drug delivery systems (SMEDDS) is one of the major trends to promote the transformation of self-microemulsion technology into industrialization. Here, a preliminary curcumin SMEDDS formulation was constructed to improve the druggability of curcumin, through the determination of equilibrium solubility determination, self-emulsifying grading assessment, and pseudo-ternary phase diagrams drafting. Furthermore, the optimal curcumin SMEDDS formulation consisted of 10% Ethyl oleate, 57.82% Cremophor RH 40, and 32.18% Transcutol P was obtained by the simplex lattice design. Besides, curcumin solid self-microemulsifying drug delivery system (S-SMEDDS) was developed by the extrusion and spheronization process to achieve the solidification of SMEDDS. The formulation of curcumin S-SMEDDS pellets was screened by the single factor experiment and the process parameters were investigated using the orthogonal optimization method. Subsequently, curcumin S-SMEDDS pellets were evaluated by apparent morphology characterization, redispersibility study, drug release behavior, and pharmacokinetic evaluation. Results from the pharmacokinetic study in rabbits showed that the AUC0–τ of the curcumin S-SMEDDS pellets and curcumin suspension were 5.91 ± 0.28 µg/mL·h and 2.05 ± 0.04 µg/mL·h, while the relative bioavailability was 289.30%. These studies demonstrated that S-SMEDDS pellets can be a promising strategy for curcumin industrialized outputs.
研究领域:
药学
·
药物递送系统
·
药代动力学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2018
·Vol. 32
·期 6
·e4192
·
IF 1.688
Dan Li,Gang Zhao,Weipeng Ai,Gao Li,Luqin Si,Jiangeng Huang,Yunzhou Chen,Sanlan Wu
In this study, a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the anticancer drugs etoposide and paclitaxel in mouse plasma and tissues including liver, kidney, lung, heart, spleen and brain. The analytes were extracted from the matrices of interest by liquid–liquid extraction using methyl tert -butyl ether–dichloromethane (1:1, v/v). Chromatographic separation was achieved on an Ultimate XB-C 18 column (100 × 2.1 mm, 3 μm) at 40°C and the total run time was 4 min under a gradient elution. Ionization was conducted using electrospray ionization in the positive mode. Stable isotope etoposide-d3 and docetaxel were used as the internal standards. The lower limit of quantitation (LLOQ) of etoposide was 1 ng/g tissue for all tissues and 0.5 ng/mL for plasma. The LLOQ of paclitaxel was 0.4 ng/g tissue and 0.2 ng/mL for all tissues and plasma, respectively. The coefficients of correlation for all of the analytes in the tissues and plasma were >0.99. Both intra- and inter-day accuracy and precision were satisfactory. This method was successfully applied to measure plasma and tissue drug concentrations in mice treated with etoposide and paclitaxel-loaded self-microemulsifying drug-delivery systems.
研究领域:
药物分析
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肿瘤学
·
药代动力学
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DOI
PubMed
高影响因子
ACS Omega
·
2025
·
IF 4.3
Shixi Li,Xuhua Liang,Jiale Xing,Min Cheng,Xue Liu,Rong Zheng,Ruya Feng
Phillyrin has many effects, such as reducing blood lipids, anti-inflammatory properties, lowering blood pressure, and decreasing tyrosinase activity. However, the bioavailability of phillyrin with oral administration is very low due to its poor water solubility. In order to overcome the bioavailability problems of phillyrin, a phillyrin self-microemulsion was prepared by changing the dosage form, the preparation process of which was optimized, and its characterizations were investigated. Based on a self-microemulsion administration system, appropriate ingredients were chosen first on the basis of a solubility test, and the range of application of each ingredient was determined by ternary phase diagrams. Second, the formula of the phillyrin self-microemulsion was optimized through the response surface method by using the mass percentage of ethyl oleate and Km value (the ratio between surfactant and cosurfactant) as independent variables and using the encapsulation efficiency (EE), grain size, and polydispersity index (PDI) as dependent variables. The average grain size, PDI, and encapsulation efficiency of the optimized microemulsion are 42.37 nm, 0.244, and 69.51%, respectively. Finally, the apparent properties, stability, and pharmic content of the prepared phillyrin self-microemulsion were characterized. Moreover, in vitro dissolution was analyzed by using the rotatory-basket method, proving the self-microemulsion could improve the in vitro dissolution of phillyrin. The above-mentioned results indicated that self-microemulsion could be used to improve the solubility and bioavailability of phillyrin, which might be a good alternative solution to improve the oral utilization of phillyrin.
研究领域:
药剂学
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药物递送
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分子药理学
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药物代谢
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Yimei Zheng,Boyu Chen,Xuanxiang Huang,Xiamei Tao,Chao Ai,Yanan Zhao,Peng Liang,Lei Chen
To enhance the stability and anti-inflammatory efficacy of dihydromyricetin (DYM), suitable excipients were selected for the development of a self-microemulsifying drug delivery system (SMEDDS). The formulated SMEDDS exhibited remarkable drug loading (117.47 ± 4.5 mg/g) and encapsulation rates (93.98 ± 3.6 %). Transmission electron microscope (TEM) revealed the nanoscale and spherical morphology of DYM-SMEDDS. Stability assessments demonstrated that DYM-SMEDDS maintained a consistent uniform small particle size after various cycles of exposure. In vitro release curve exhibited that DYM-SMEDDS released 91.27 ± 1.44 % of DYM within 24 h, surpassing the suspension by 2-fold. Furthermore, in vivo studies indicated that DYM-SMEDDS significantly inhibited the levels of pro-inflammatory factors, while promoting the activity of antioxidant enzymes (p < 0.05). These findings underscore the preventive effects of DYM-SMEDDS against inflammation induced by lipopolysaccharide in mice. In conclusion, SMEDDS exhibits promising potential for oral administration, providing an effective platform for enhancing the efficacy of poorly soluble flavonoids.
研究领域:
药剂学
·
炎症研究
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF FOOD SCIENCE
·
2017
·Vol. 82
·期 12
·2901-2909
·
IF 1.815
Ruixue Guo,Xinbo Guo,Xiaodan Hu,Arshad Mehmood Abbasi,Lin Zhou,Tong Li,Xiong Fu,Rui Hai Liu
The purpose of this work was to improve the oral bioavailability of a poorly soluble functional food ingredient, the total flavones of Hippophaë rhamnoides L. (TFH). A self-microemulsion drug delivery system (SMEDDS) was developed to overcome the problems of poor absorption of TFH in vivo . The optimal SMEDDS significantly enhanced the solubility of TFH up to 530 times compared to that in water. The mean droplet size was 61.76 nm with uniform distribution. And the loaded system was stable at 25 °C for 3 mo with transparent appearance. The in vitro release of TFH from SMEDDS was faster and more complete than that from suspension. After oral administration of TFH–SMEDDS in rats, the relative bioavailability of TFH was dramatically improved for 3.09 times compared with the unencapsulated form. The investigation indicated the potential application of SMEDDS as a vehicle to improve the oral bioavailability of TFH. Practical Application The lipid-based nanotechnology, namely self-microemulsion drug delivery system (SMEDDS) was used to improve the bioavailability and oral delivery of total flavones of Hippophaë rhamnoides L. (TFH). The relevant bioavailability of TFH could be remarkably 3-fold improved by the optimized SMEDDS. The SMEDDS produced via a simple one-step process for poorly soluble TFH to achieve a significant improvement in the bioavailability, may endorse the promising utilization of TFH in functional foods as well as pharmaceutical fields with an enhanced absorption in vivo .
研究领域:
药剂学
·
功能性食品科学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2024
·
IF 5.7
Huang Xingzhen,Feng Lizhen,Lu Xuefang,Yang Fan,Liu Shengjun,Wei Xueqian,Huang Jinping,Wang Yao,Huang Dongyi,Huang Tingting
In this study, we developed a novel co-administration of curcumin and sorafenib using a Self micro-emulsifying Drug Delivery System (SMEDDS) called Sorafenib-Curcumin Self micro-emulsifying Drug Delivery System (SOR-CUR-SMEDDS). The formulation was optimized using star point design-response surface methodology, and in vitro cellular experiments were conducted to evaluate the delivery ratio and anti-tumor efficacy of the curcumin and sorafenib combination. The SOR-CUR-SMEDDS exhibited a small size distribution of 13.48 ± 0.61 nm, low polydispersity index (PDI) of 0.228 ± 0.05, and negative zeta potential (ZP) of − 12.4 mV. The half maximal inhibitory concentration (IC 50 ) of the SOR-CUR-SMEDDS was 3-fold lower for curcumin and 5-fold lower for sorafenib against HepG2 cells (human hepatocellular carcinoma cells). Transmission electron microscopy (TEM) and particle size detection confirmed that the SOR-CUR-SMEDDS droplets were uniformly round and within the nano-emulsion particle size range of 10–20 nm. The SMEDDS were characterized then studied for drug release in vitro via dialysis membranes. Curcumin was released more completely in the combined delivery system, showing the largest in vitro drug release (79.20%) within 7 days in the medium, while the cumulative release rate of sorafenib in the release medium was low, reaching 58.96% on the 7 day. In vitro pharmacokinetic study, it demonstrated a significant increase in oral bioavailability of sorafenib (1239.88-fold) and curcumin (3.64-fold) when administered in the SMEDDS. These findings suggest that the SMEDDS formulation can greatly enhance drug solubility, improve drug absorption and prolong circulation in vivo, leading to increased oral bioavailability of sorafenib and curcumin. Graphical abstract
研究领域:
药剂学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2024
·Vol. 25
·期 8
·1-18
·
IF 3.4
Zou Zhihui,Xue Yuanyuan,Adu-Frimpong Michael,Wang ChengWei,Jin Zhou,Xu Ying,Yu Jiangnan,Xu Ximing,Zhu Yuan
This study aimed to construct a self-microemulsion drug delivery system (SMEDDS) for Formononetin (FMN) to improve its solubility and bioavailability while combining the nanocrystals (NCs) technology. The SMEDDS prescription composition was optimized with a pseudo-three-phase diagram, followed by a series of in vitro and in vivo evaluations of the selected optimal prescriptions. FMN-NCs loaded SMEDDS showed a homogeneous spherical shape in the Transmission electron microscope and the particle size was measured as (20.65 ± 1.42) nm. The in vitro cumulative release rate in each dissolution medium within 30 min was higher than 80%, much higher than that of FMN (6%) and FMN-NCs (40%); Cellular experiments confirm that the formulation has a high safety profile and significantly promotes cellular uptake. The results of pharmacokinetics and intestinal absorption in rats showed that the relative bioavailability of FMN-NCs and FMN-NCs loaded SMEDDS were (154.80 ± 3.76)% and (557.73 ± 32.88)%, respectively, and both of them significantly increased the rate and extent of absorption of the drug in intestinal segments. FMN-NCs loaded SMEDDS significantly enhanced the solubility and bioavailability of FMN. Graphical
研究领域:
药剂学
·
药物递送
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2017
·
IF 3.756
Li Chen,Chang-shun Liu,Qing-zhen Chen,Sen Wang,Yong-ai Xiong,Jing Jing,Jia-jia Lv
The purpose of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of Chlorogenic acid (CA), an important bioactive compound from Lonicerae Japonicae Flos with poor permeability. SMEDDS was prepared and characterized by self-emulsifying rate, morphological observation, droplet size determination, stability, in vitro release, in vivo bioavailability and tissue distribution experiments. Results shown that the SMEDDS of CA has a high self-emulsifying rate (> 98%) in the dissolution media, and its microemulsion exhibits small droplet size (16.37 nm) and good stability. In vitro release test showed a complete release of CA from SMEDDS in 480 min. After oral administration in mice, significantly enhanced bioavailability of CA was achieved through SMEDDS (249.4% relative to the CA suspension). Interestingly, SMEDDS significantly changed the tissue distribution of CA and showed a better targeting property to the kidney (2.79 of the relative intake efficiency). It is suggested that SMEDDS improves the oral bioavailability of CA may mainly through increasing its absorption and slowing the metabolism of absorbed CA via changing its distribution from the liver to the kidney. In conclusion, it is indicated that SMEDDS is a promising carrier for the oral delivery of CA.
研究领域:
药剂学
·
药物代谢动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2022
·Vol. 23
·期 4
·1-16
·
IF 4.026
Gu Zhengqing,Xue Yuanyuan,Li Shuang,Adu-Frimpong Michael,Xu Ying,Yu Jiangnan,Xu Ximing,Zhu Yuan
Diosmetin (DIOS) is a functional compound with poor water solubility, bad permeability, and crystal form. Self-microemulsifying drug delivery system (SMEDDS) was an effective formulation to overcome these shortcomings. In this study, liquid SMEDDS was prepared using Capmul® MCM C8 EP/NF, Cremophor EL, and PEG 400 (2:5.6:2.4, w/w/w) as excipients. Then, the novel technology of electrospray solidified liquid SMEDDS and prepared solid SMEDDS for inhibiting crystallization. Polyvinyl pyrrolidone (PVP) was used as carrier to construct DIOS-loaded solid SMEDDS, with polyethylene oxide (PEO) contributing to the formation of regular sphere in the process of spinning. The particle size of solid SMEDDS (194 ± 5 nm) was much bigger than of liquid SMEDDS (25 ± 1 nm), while DIOS-loaded solid SMEDDS showed greater dissolution rates in pH 1.2 and pH 6.8 media through in vitro drug release study. The solid nanoparticles were smooth and uniform from the graph of a scanning electron microscope (SEM). The graph of a transmission electron microscope (TEM) showed that small droplets were loaded in the matrix. Furthermore, DIOS was encapsulated by matrix in amorphous state via differential scanning calorimetry (DSC) and attenuated total reflection Fourier transform infrared (ATR-FTIR). The crystalline of DIOS was not formed in solid SMEDDS due to the characteristic peaks of DIOS disappeared in X-ray diffraction (XRD) pattern. Therefore, the oral bioavailability of DIOS improved significantly compared with liquid SMEDDS (4.27-fold). Hence, solid SMEDDS could improve the solubility and bioavailability of DIOS, through transfer of the state of crystalline to amorphous by electrospray technology.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2020
·Vol. 21
·期 8
·1-10
·
IF 2.401
Li Ruiming,Wang Yong,Yang Qiang,Lai Baolong,Zhou Xie,Feng Min
10-Hydroxycamptothecin (HCPT) is a DNA inhibitor of topoisomerase I and exerts antitumor activities against various types of cancer. However, reversible conversion from a pharmacologically active lactone form to an inactive carboxylate form of HCPT and poor water solubility hamper its clinical applications. To overcome these shortcomings, we designed a fine self-microemulsifying drug delivery system (SMEDDS) for HCPT to effectively protect HCPT in its active lactone form as well as improving dissolution rates. A formulation of HCPT-SMEDDS that contained ethyl oleate, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), and polyethylene glycol 400 (PEG400) was optimized by using the central composite design and response surface methodology. Following 1:100 aqueous dilution of the optimized HCPT-SMEDDS, the droplet size of resulting microemulsions was 25.6 ± 0.7 nm, and the zeta potential was − 15.2 ± 0.4 mV. The optimized HCPT-SMEDDS appeared to stabilize the lactone moiety of HCPT with 73.6% being present in the pharmacologically active lactone forms in simulated intestinal fluid, but only 45.7% for free HCPT. Furthermore, the physically stable formulation showed the active lactone form predominated in HCPT-SMEDDS (> 95%) for 6 months under the accelerated storage condition. Meanwhile, the optimized SMEDDS formulation also significantly improved dissolution rates and membrane permeability of the lactone form of HCPT. Therefore, HCPT-SMEDDS involved designing for the ease of manufacture, and provided a potent oral dosage form for preserving its active lactone form as well as enhancing the dissolution rate.
研究领域:
药剂学
·
肿瘤学
·
生物制药
✓ 已验证
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2019
·
IF 2.367
Qiuxuan Yang,Qilong Wang,Yingshu Feng,Qiuyu Wei,Congyong Sun,Caleb Kesse Firempong,Michael Adu-Frimpong,Ran Li,Rui Bao,Elmurat Toreniyazov,Hao Ji,Jiangnan Yu,Ximing Xu
The prevalence of hyperuricemia is relatively high worldwide, and a great number of patients are suffering from its complications. 6-shogaol, an alkylphenol compound purified from the root of ginger (Zingiber officinale Roscoe), has been proved to possess diverse pharmacological activities. However, its poor aqueous solubility usually leads to low bioavailability, and further clinical applications will be greatly discounted. The current study aimed to formulate a 6-shogaol-loaded-Self Microemulsifying Drug Delivery System (SMEDDS) to amend low aqueous solubility and bioavailability orally, as well as, potentiate the hyperuricemic activity of the 6-shogaol. SMEDDS was developed with central composite design established on a two system components viz., 18.62% W/W ethyl oleate (oil phase) and ratio of tween 80 (surfactant) to PEG 400 (co-surfactant) (1.73:1, W/W). Based on quadratic model, the navigation of the design space could generate spherically-shaped and homogenous droplets with respective mean particle diameter, polydispersity and of 20.00 ± 0.26 nm and 0.18 ± 0.02. The 6-shogaol-SMEDDS showed significant elevation of cumulative release compared with the free 6-shogaol and more importantly a 571.18% increment in the relative oral bioavailability of the drug. The predominant accumulation of 6-shogaol-SMEDDS in the liver suggested hepatic-targeting potentiality of the drug. Oral administration of 6-shogaol-SMEDDS in hyperuricemic rats also significantly decreased uric acid level and xanthine oxidase activity. Histological studies confirmed formulation groups indeed could provide better protection of kidney than free drug groups. Collectively, these findings indicated that the SMEDDS hold much promise in enhancing the oral delivery and therapeutic efficacy of 6-shogaol.
研究领域:
药剂学
·
代谢病学
·
中药学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 36
·22280-22285
·
IF 3.108
Yuxia Zhang,Yan Bai,Huali Chen,Yuanrui Huang,Pei Yuan,Liangke Zhang
A colon-specific capsule with alginate beads containing a self-microemulsifying drug delivery system (SMEDDS) was developed and evaluated. The SMEDDS technique was used to improve the solubility of curcumin (Cur). After encapsulating the Cur-loaded SMEDDS, the alginate beads were placed inside an impermeable capsule body. A konjac glucomannan/lactose/hydroxypropyl methylcellulose (KG/Lac/HPMC) plug tablet was then prepared and placed in the mouth of the capsule. The capsule demonstrated a pulsatile drug-release profile with a specific lag time and subsequent sustained-release phase. The lag time was modified by changing the type of HPMC and the ratio of KG/Lac/HPMC. In addition, 0.5% β-mannase solution and 5% rat cecal solution were used to simulate the colon fluid, significantly decreasing the lag time of the capsule. The results show that the capsule has potential for use in colon-specific drug delivery and exhibits a sustained-release characteristic.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）