The United States Pharmacopeia (USP) General Chapters Dissolution 〈711〉 and Disintegration and Dissolution of Dietary Supplements 〈2040〉 allows the use of enzymes in dissolution media when gelatin capsules do not conform to dissolution specifications due to cross linking. Possible interactions between enzymes and surfactants when used together in dissolution media could result in loss of the enzymatic activity. Pepsin is an enzyme commonly used in dissolution media, and in this work, the activity of pepsin was determined in the presence of different surfactants as usually found in case of dissolution tests of certain gelatin capsule formulations.Pepsin enzymatic activity was determined according to the Ninth Edition of the Food Chemicals Codex (FCC) 9 method, in dissolution conditions: simulated gastric fluid, 37 °C and 50 rpm. Sodium dodecyl sulfate (SDS), cetyltrimethyl ammonium bromide (CTAB), polysorbate 80 (Tween 80) and octoxynol 9 (Triton X100) in concentrations above and below their critical micellar concentrations were selected. Results showed a significant reduction in the activity of pepsin at all the concentrations of SDS assayed. On the contrary, CTAB, Tween 80, and Triton X100 did not alter the enzymatic activity at of pepsin any of the concentration assayed.This data demonstrates a rational selection of the surfactant to be used when pepsin is required in dissolution test. 相似文献
Risedronate is a nitrogen-containing bisphosphonate for the treatment and prevention of postmenopausal osteoporosis. The current work aims to develop a novel green HPLC-UV method for the rapid analysis of risedronate sodium in bulk and tablet formulation. The analyzed samples were separated on Waters Atlantis dC18 (150 mm × 3.9 mm; 5 μm) column using a green mobile phase consisting of potassium phosphate buffer pH 2.9 and potassium edetate buffer pH 9.5 in a ratio of 1:2, the final pH was adjusted to 6.8 with phosphoric acid, the mobile phase was pumped at a rate of 1.0 mL/min, with column temperature set at 30 °C, eluted samples were detected at 263 nm and the chromatographic run time was 3.0 min. The method was found to be linear over the concentration range of 14–140 μg/mL with a correlation coefficient (r2) of 0.9994. Accuracy and precision were evaluated from three QC samples (LQC, MQC and HQC) together with the five calibrators where the percentage accuracy was found to be 101.84%. Processed quality control samples of risedronate sodium were tested for stability at different conditions, short term, long term and freeze- thaw stability. The current method was further extended to study the content uniformity of Actonel® tablets following United States Pharmacopoeia (USP) guidelines. The proposed method was fully validated as per ICH guidelines. 相似文献
Solvent evaporation method for preparation of nanomatrix has the disadvantages, such as residual organic solvent, environmental pollution, explosion-proofing and so on. To overcome these shortcomings, a series of fenofibrate nanomatrix drug delivery system (NDDS) consisting of nano-porous silica Sylysia®350 (S350) and pH sensitive material Eudragit® L100-55 (EL100-55) were prepared using hot-melt extrusion (HME), and their in vitro dissolution and in vivo bioavailability were compared. Finally, the formulation with the highest in vivo bioavailability was selected as the optimized formulation for DSC and PXRD characterization. The results showed that the optimized NDDS showed a higher bioavailability than the reference formulation, although there was crystalline form drug remaining in NDDS. The relative bioavailability of the optimized formulation was 157.1% compared with the commercial product Lipanthyl®. In addition, the relative bioavailability of the optimized formulation was 124.8% in comparison with the formulation prepared by solvent evaporation method, showing that the NDDS prepared by the HME method was effective in improving the bioavailability of fenofibrate. In conclusion, HME was a promising method to prepare NDDS. 相似文献
Background: Leptomeningeal metastases (LM), associated with poor prognosis, are frequent complications of advanced non-small cell lung cancer (NSCLC) patients, especially in patients with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the mutational landscape of LM has not been comprehensively investigated in large cohorts and the underlining biology of LM remains elusive. Some studies have explored the potential of cerebrospinal fluid (CSF) in reflecting the molecular profile of LM but with limited number of patients enrolled.
Methods: In this study, we performed capture-based targeted sequencing using a panel consisting of 168 lung cancer-related genes on matched CSF and plasma samples from 72 advanced NSCLC patients with confirmed LM to interrogate the potential of CSF as a source of liquid biopsy.
Results: We revealed a rate of detection of 81.5% and 62.5% for CSF and plasma, respectively (p = 0.008). The maximum allelic fraction (MaxAF) was also significantly higher in CSF (43.6% vs. 4.6%) (p < 0.001). CSF, harboring a unique genomic profile by having a significant number of CSF-specific mutations, primarily copy number variations, is superior to plasma in reflecting the mutational profile of LM. Further pathway enrichment analysis revealed that most of CSF-specific mutations participated in pathways relevant to the tumorigenesis and the development of metastases. Moreover, our data also revealed that TP53 loss of heterozygosity (LOH) predominantly existed in CSF (p < 0.001).
Conclusions: Collectively, we demonstrated that CSF provides a more comprehensive profile of LM than plasma in a large cohort, thus can be used as an alternative source of liquid biopsy for LM patients. 相似文献
BackgroundTryptophan catabolites (“TRYCATs”) produced by the kynurenine pathway (KP) may play a role in depression pathophysiology. Studies comparing TRYCATs levels in depressed subjects and controls provided mixed findings. We examined the association of TRYCATs levels with 1) the presence of Major Depressive Disorder (MDD), 2) depressive symptom profiles and 3) inflammatory markers.MethodsThe sample from the Netherlands Study of Depression and Anxiety included participants with current (n = 1100) or remitted (n = 753) MDD DSM-IV diagnosis and healthy controls (n = 642). Plasma levels of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KynA), quinolinic acid (QA), C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured. Atypical/energy-related symptom (AES), melancholic symptom (MS) and anxious-distress symptom (ADS) profiles were derived from questionnaires.ResultsAfter adjustment for age, sex, education, smoking status, alcohol consumption and chronic diseases, no significant differences in TRYCATs were found comparing MDD cases versus controls. The MS profile was associated (q < 0.05) with lower KynA (β = -0.05), while AES was associated with higher KYN (β = 0.05), QA (β = 0.06) and TRP (β = 0.06). Inflammatory markers were associated with higher KYN (CRP β = 0.12, IL-6 β = 0.08, TNF β = 0.10) and QA (CRP β = 0.21, IL-6 β = 0.12, TNF β = 0.18). Significant differences against controls emerged after selecting MDD cases with high (top 30%) CRP (KYN d = 0.20, QA d = 0.33) and high TNF (KYN d = 0.24; QA d = 0.39).ConclusionsTRYCATs levels were related to specific clinical and biological features, such as atypical symptoms or a proinflammatory status. Modulation of KP may potentially benefit a specific subset of depressed patients. Clinical studies should focus on patients with clear evidence of KP dysregulations. 相似文献
The amorphization of 18 different drugs on milling with one mole equivalent sodium taurocholate (NaTC) was investigated. In all cases the X-ray powder pattern showed an amorphous halo after milling at room temperature or after cryomilling and 14 of the 18 coamorphous drug-NaTC systems were physically stable for between one to eleven months under ambient storage conditions. In three cases, namely carbamazepine-NaTC, indomethacin-NaTC and mefenamic acid-NaTC, significant dissolution advantages over the crystalline drugs were observed, both for the freshly prepared samples and after storage for seven months. To understand the increased physical stability, infrared-, near-infrared and Raman spectroscopic studies were carried out. The effectiveness of NaTC as a coformer in a diverse range of coamorphous systems is attributed to its awkward molecular shape that hampers recrystallization and phase separation and its propensity to form a range of similar, yet different drug-coformer hydrogen bonding arrangements. 相似文献