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
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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
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
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产品关联
DOI
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
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生物医学工程
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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
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肿瘤学
·
生物制药
✓ 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
AAPS PHARMSCITECH
·
2021
·Vol. 22
·期 1
·1-16
·
IF 3.246
Sun Congyong,Li Wenjing,Zhang Huiyun,Adu-Frimpong Michael,Ma Ping,Zhu Yuan,Deng Wenwen,Yu Jiangnan,Xu Ximing
This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the solubility, oral bioavailability, and hypolipidemic effects of syringic acid (SA), a bioactive and poorly-soluble polyphenol. Based on the response surface methodology-central composite design (RSM-CCD), an optimum formulation of SA-SMEDDS, consisting of ethyl oleate (oil, 12.30%), Cremophor-EL (surfactant, 66.25%), 1,2-propanediol (cosurfactant, 21.44%), and drug loading (50 mg/g), was obtained. The droplets of SA-SMEDDS were nanosized (16.38 ± 0.12 nm), spherically shaped, and homogeneously distributed (PDI = 0.058 ± 0.013) nanoparticles with high encapsulation efficiency (98.04 ± 1.39%) and stability. In vitro release study demonstrated a prolonged and controlled release of SA from SMEDDS. In vitro cell studies signified that SA-SMEDDS droplets substantially promoted cellular internalization. In comparison with the SA suspension, SA-SMEDDS showed significant prolonged T max , t 1/2 , and MRT after oral administration. Also, SA-SMEDDS exhibited a delayed in vivo elimination, increased bioavailability (2.1-fold), and enhanced liver accumulation. Furthermore, SA-SMEDDS demonstrated significant improvement in alleviating serum lipid profiles and hepatic steatosis in high-fat diet-induced hyperlipidemia in mice. Collectively, SMEDDS demonstrated potential as a nanosystem for the oral delivery of SA with enhanced bioavailability and hypolipidemic effects.
研究领域:
药剂学
·
药物递送
·
脂质代谢
·
生物药剂学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2018
·
IF 1.883
Mengyuan Cao,Xu Xue,Xixi Pei,Yiwen Qian,Lan Liu,Lili Ren,Guoguang Chen
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.
研究领域:
药剂学
·
药物代谢
·
生物制药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2016
·
IF 3.973
Yang Xu,Qilong Wang,Yingshu Feng,Caleb Kesse Firempong,Yuan Zhu,Emmanuel Omari-Siaw,Yuanyuan Zheng,Zunqin Pu,Ximing Xu,Jiangnan Yu
The purpose of this study was to develop a [6]-Gingerol-loaded self-microemulsifying drug delivery system ([6]-Gingerol-SMEDDS) for oral administration and enhanced bioavailability of the drug. The [6]-Gingerol-SMEDDS, consisting of oils (ethyl oleate), surfactant (Cremophor EL35) and co-surfactant (1,2-propanediol), showed an acceptable spherical nanoparticle with stable physicochemical properties such as the mean droplet size (73.06 ± 0.49 nm), zeta potential (−2.45 ± 0.41) and encapsulation efficiency (89.40 ± 1.11%). The in vitro release of [6]-Gingerol from the delivery system in the three different media (HCl, pH 1.2; Double distilled water, pH 7.0; phosphate buffer solution, pH 7.4) was significantly higher than in the free drug. The [6]-Gingerol-SMEDDS also exhibited prolonged plasma circulation which led to 6.58-fold increase in oral bioavailability compared with the free drug. These findings indicated that the developed [6]-Gingerol-SMEDDS could be a promising alternative in improving the solubility and oral bioavailability of [6]-Gingerol, as well as increasing its biological applications.
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
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Ping Song,Yuan Tian,Guizhou Hao,Lisa Xu,Yan Sun,Yong Sun
Ibrutinib is an anti-cancer drug, mainly used for treating B-cell malignancies. Because of its low water solubility and poor absorption in vivo , the bioavailability is extremely low, only 2.9%. In this study, a solid self-microemulsifying drug delivery system based on the lipid matrix was designed and prepared for ibrutinib. The composition of the self-microemulsion of ibrutinib includes oil phase Caprylic/Capric Triglyceride (Captex®335), surfactant Tween-80, and co-surfactant Diethylene glycol monoethyl ether (Transcutol HP). And the mesoporous silica SBA-15 was selected as an adsorbent to prepare solid powder preparations using the spray-drying method, which significantly improved its dispersibility and stability, and contributed to reducing the particle size and long-term preservation in gastric and intestinal fluids. The in vivo pharmacokinetic study of beagles showed that compared with commercial ibrutinib capsules , the relative oral bioavailability of ibrutinib capsules based on lipid matrix increased to 467.60%. In summary, the lipid-based solid preparation is a promising platform that can effectively improve the oral absorption of ibrutinib.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
高影响因子
AAPS PHARMSCITECH
·
2014
·Vol. 15
·期 3
·731-740
·
IF 1.776
Zhang Jianbin,Lv Yan,Zhao Shan,Wang Bing,Tan Mingqian,Xie Hongguo,Lv Guojun,Ma Xiaojun
The objective of this study is to investigate the effect of lipolysis on the release of poorly water-soluble drug from SMEDDS in the perspective of drug core/shell location. For this purpose, four SMEDDS formulations with various core/shell properties were developed based on long-chain lipid or medium-chain lipid as well as different surfactant/oil ratios. Poorly water-soluble drugs, hymecromone and resveratrol, were significantly solubilized in all SMEDDS formulations and the diluted microemulsions. Fluorescence spectra analysis indicated that hymecromone was mainly located in the shell of microemulsions, while resveratrol was located in the core. The effect of lipolysis on the release rates of drugs with different core/shell locations were investigated by a modified in vitro drug release model. For the drug located in the shell, hymecromone, the release profiles were not affected during the lipolysis process and no significant differences were observed among four formulations. For the drug located in the core, resveratrol, the release rates were increased to various degrees depending on the extent of digestion. In conclusion, the drug core/shell location plays an important role for determining the effect of lipolysis on drug release from SMEDDS formulation.
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
·
2019
·Vol. 20
·期 5
·1-11
·
IF 2.608
Zhang Kangyi,Wang Qilong,Yang Qiuxuan,Wei Qiuyu,Man Na,Adu-Frimpong Michael,Toreniyazov Elmurat,Ji Hao,Yu Jiangnan,Xu Ximing
The aim of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) for enhancement of the oral bioavailability of isoliquiritigenin (ISL) as well as evaluate its in vivo anti-hyperuricemic effect in rats. The ISL-loaded self-microemulsifying drug delivery system (ISL-SMEDDS) was comprised of ethyl oleate (EO, oil phase), Tween 80 (surfactant), and PEG 400 (co-surfactant). The ISL-SMEDDS exhibited an acceptable narrow size distribution (44.78 ± 0.35 nm), negative zeta potential (− 10.67 ± 0.86 mV), and high encapsulation efficiency (98.17 ± 0.24%). The in vitro release study indicated that the release rates of the formulation were obviously higher in different release media (HCl, pH 1.2; PBS, pH 6.8; double-distilled water, pH 7.0) compared with the ISL solution. The oral bioavailability of the ISL-SMEDDS was enhanced by 4.71 times in comparison with the free ISL solution. More importantly, ISL-SMEDDS significantly reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in the model rats. Collectively, the prepared ISL-SMEDDS proved to be potential carriers for enhancing the solubility and oral bioavailability of ISL, as well as ameliorating its anti-hyperuricemic effect.
研究领域:
药剂学
·
生物药剂学
·
药物代谢动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2021
·Vol. 22
·期 3
·1-12
·
IF 3.246
Zhang Xueting,Chen Zhenzhen,Tao Chun,Zhang Jing,Zhang Minxin,Zhang Jialiang,Liu Zhihong,Lin Jiao,Xu Hang,Zhang Qian,Song Hongtao
The combination of self-microemulsifying drug delivery system (SMEDDS) and mesoporous silica materials favors the oral delivery of poorly water-soluble drugs (PWSD). However, the influence of the surface property of the mesopores towards the drug release and in vivo pharmacokinetics is still unknown. In this study, SBA-15 with hydroxyl groups (SBA-15-H), methyl groups (SBA-15-M), amino groups (SBA-15-A), or carboxyl groups (SBA-15-C) was combined with SMEDDS containing sirolimus (SRL). The diffusion and self-emulsifying of SMEDDS greatly improved the drug release over the raw SRL and SRL-SBA-15-R (R referred to as the functional groups). Results of drug absorption and X-ray photoelectron spectroscopy (XPS) showed strong hydrogen binding between SRL and the amino groups of SBA-15-A, which hindered the drug release and oral bioavailability of SRL-SMEDDS-SBA-15-A. The favorable release of SRL-SMEDDS-SBA-15-C (91.31 ± 0.57%) and SRL-SMEDDS-SBA-15-M (91.76 ± 3.72%) contributed to enhancing the maximum blood concentration (C max ) and the area under the concentration-time curve (AUC 0→48 ). In conclusion, the release of SRL-SMEDDS-SBA-15-R was determined by the surface affinity of the SBA-15-R and the interaction between the SRL molecules and the surface of SBA-15-R. This study suggested that the SMEDDS-SBA-15 was a favorable carrier for PWSD, and the surface property of the mesopores should be considered for the optimization of the SMEDDS-SBA-15. Graphical abstract
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
危险品化学品经营许可证（带存储）