2-Methyloxolane as an effective bio-based solvent for the removal of ßN-alkanoyl-5-hydroxytryptamines from Arabica green coffee beans.

ßN-alkanoyl-5-hydroxytryptamines (Cn-5HTs) are the main constituents of coffee wax and may be responsible for the increased severity of gastric disorders in sensitive consumers. Their removal from green coffee beans can result in a "stomach-friendly" brew. This work presents a green approach to Cn-5HTs extraction using the bio-based solvent 2-methyloxolane (2-MeOx). HPLC/DAD analyses on Arabica Brazil samples show that mild conditions (30 min at 50 °C) extract about 90% of the wax, without affecting the caffeine content of the beans, whereas almost complete removal is achieved in 60 min at reflux. 2-MeOx forms an azeotrope with water, its possible re-use has been demonstrated using aqueous 2-MeOx (95.5%) as the solvent. These preliminary results make 2-MeOx a possible candidate for the replacement of dichloromethane (DCM) in coffee dewaxing. The importance of fermentation in reducing Cn-5HTs by about 36% has been demonstrated in an analysis of green beans subjected to different post-harvest treatments.

Development and in vitro Evaluation of Gastro-protective Aceclofenac-loaded Self-emulsifying Drug Delivery System.

AIM: Chronic use of oral nonsteroidal anti-inflammatory drugs (NSAIDs) is commonly associated with gastric irritation and gastric ulceration. Therefore, the aim of study was to develop a novel oral drug delivery system with minimum gastric effects and improved dissolution rate for aceclofenac (ACF), a model BCS class-II drug. METHODS: Self-emulsifying drug delivery systems (SEDDS) were formulated to increase the solubility and ultimately the oral bioavailability of ACF. Oleic acid was used as an oil phase, Tween 80 (T80) and Kolliphor EL (KEL) were used as surfactants, whereas, polyethylene glycol 400 (PEG 400) and propylene glycol (PG) were employed as co-surfactants. Optimized formulations (F1, F2, F3 and F4) were analyzed for droplet size, poly dispersity index (PDI), cell viability studies, in vitro dissolution in both simulated gastric fluid and simulated intestinal fluid, ex vivo permeation studies and thermodynamic stability. RESULTS: The optimized formulations showed mean droplet sizes in the range of 111.3 ± 3.2 nm and 470.9 ± 12.52 nm, PDI from 244.6 nm to 389.4 ± 6.51 and zeta-potential from -33 ± 4.86 mV to -38.5 ± 5.15 mV. Cell viability studies support the safety profile of all formulations for oral administration. The in vitro dissolution studies and ex vivo permeation analysis revealed significantly improved drug release ranging from 95.68 ± 0.02% to 98.15 ± 0.71% when compared with control. The thermodynamic stability studies confirmed that all formulations remain active and stable for a longer period. CONCLUSION: In conclusion, development of oral SEDDS might be a promising tool to improve the dissolution of BCS class-II drugs along with significantly reduced exposure to gastric mucosa.

One-step preparation of ibuprofen fast- and sustained-release formulation by electrospinning with improved efficacy and reduced side effect.

In this study, we developed a one-step method to prepare ibuprofen fast- and sustained-release complex preparation. It was based on a double jets electrospinning process. Ibuprofen, a poorly water-soluble drug, was electrospun into fibers with polyvinyl pyrrolidone and hydroxypropyl methyl cellulose by two jets, respectively. The complex preparation had an enough initial dose come from fast-release part and a maintenance dose come from sustained-release part. Through the study of X-ray diffraction, differential scanning colorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM), it was confirmed that ibuprofen was highly dispersed in nanofibers (NFs) in amorphous state. Because one line of NFs was very thin and could only extend along two directions, it was difficult for ibuprofen to transform from amorphous to crystal in this kind of approximate one-dimensional structure. Additionally, it was confirmed by animal experiment that the complex preparation also had a benefit to reduce gastric irritation that usually caused by traditional oral ibuprofen preparation. Therefore, the method developed in this study was a convenient and good-quality approach for ibuprofen pain-alleviating preparation.

Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: formulation and in vitro/in vivo evaluation.

Nanoparticles (NPs) have long gained significant interest for their use in various drug formulations in order to increase bioavailability, prolong drug release, and decrease side effects of highly toxic drugs. The objective of this investigation was to evaluate the potential of ethyl cellulose-based NPs (EC-NPs) to modulate the release and reduce ulcerogenicity of piroxicam (PX) after oral administration. PX-loaded EC-NPs were prepared by solvent evaporation technique using different stabilizers at three concentration levels. Morphological examination of selected formulas confirmed the formation of spherical NPs with slightly porous surface. Formulation containing poloxamer-stabilized EC-NPs (P188/0.2), having a particle size of 240.26±29.24 nm, polydispersity index of 0.562±0.030, entrapment efficiency of 85.29%±1.57%, and modulated release of PX (88% after 12 hours), was selected as the optimum formulation. Differential scanning calorimetry demonstrated the presence of PX in an amorphous form in the NPs. Fourier-transform infrared spectroscopy revealed the possible formation of hydrogen bond and the absence of chemical interaction. In vivo study, evaluation of pharmacokinetic parameters, evaluation of gastric irritation potential, and histological examination were conducted after administration of the selected formulation. Time to reach maximum plasma concentration, t max, of poloxamer-stabilized EC-NPs was significantly higher than that of Feldene(®) 20 mg capsules (P≤0.001). Encapsulation of the acidic, gastric offender PX into NPs managed to significantly suppress gastric ulceration potential in rats (P≤0.05) as compared to that of PX suspension. A reduction of 66% in mean ulcer index was observed. In conclusion, poloxamer-stabilized EC-NPs (P188/0.2) had a significant potential of offsetting deleterious side effects common in PX use.

The role of the stomach in drug absorption as observed via absorption rate analysis.

Absorption rate analysis (ARA) was introduced in 2011 as a no-cost investigative tool for elucidating the details of drug absorption recorded in individual plasma time-concentration profiles. The method continues to be refined since its introduction, so that a new article offering more advanced applications of the method is appropriate. The stomach has been observed to exert considerable influence on the drug absorption process beyond the usual issues of drug solubility and stability in the gastric environment. This article is intended to demonstrate how readers can use ARA to reveal common factors affecting drug absorption. A newly introduced technique is to make observations concerning individual subjects, then assemble those individual observations to reveal factors not observable on an individual basis. This technique considerably increases the utility of ARA for revealing potential barriers to drug absorption.

The preparation of inclusion compound of diclofenac sodium-β-cyclodextrin / 中国药学杂志

OBJECTIVE: To prepare the inclusion compound of diclofenac sodium (DFS)-β-cyclodextrin (β-CD) and investigate its properties. METHOD: The inclusion compound of DFS-β-CD was prepared by the co-precipitation method. RESULTS: The inclusion compound of DFS-β-CD was confirmed by UV absorption spectrum, IR absorption spectroscopy, differential scanning calorimetry (DSC) and phase solubility diagram. Meanwhile, the content analysis of the inclusion compound showed that the molecular ratio of DFS to β-CD was 1∶1. CONCLUSION: The soluability and dissolution rate of DFS were increased and its irritation to stomach was reduced when the drug was included by β-CD.