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European Journal of Pharmaceutics and... Dec 2023Intestinal drug solubility is a key parameter controlling absorption after the administration of a solid oral dosage form. The ability to measure fed state solubility in...
Intestinal drug solubility is a key parameter controlling absorption after the administration of a solid oral dosage form. The ability to measure fed state solubility in vitro is limited and multiple simulated intestinal fluid recipes have been developed but with no consensus which is optimal. This study has utilised nine bioequivalent simulated fed intestinal media recipes that cover over 90% of the compositional variability of sampled fed human intestinal fluid. The solubility of 24 drugs (Acidic; furosemide, ibuprofen, indomethacin, mefenamic acid, naproxen, phenytoin, piroxicam, valsartan, zafirlukast: Basic; aprepitant, atazanavir, bromocriptine, carvedilol, dipyridamole, posaconazole, tadalafil: Neutral; acyclovir, carbamazepine, felodipine, fenofibrate, griseofulvin, itraconazole, paracetamol, probucol) has been assessed to determine if structured solubility behaviour is present. The measured solubility behaviour can be split into four categories and is consistent with drug physicochemical properties and previous solubility studies. For acidic drugs (category 1) solubility is controlled by media pH and the lowest and highest pH media identify the lowest and highest solubility in 90% of cases. For weakly acidic, basic and neutral drugs (category 2) solubility is controlled by media pH and total amphiphile concentration (TAC), a consistent solubility pattern is evident with variation related to individual drug media component interactions. The lowest and highest pH × TAC media identify the lowest and highest solubility in 70% and 90% of cases respectively. Four drugs, which are non-ionised in the media systems (category 3), have been identified with a very narrow solubility range, indicating minimal impact of the simulated media on solubility. Three drugs exhibit solubility behaviour that is not consistent with the remainder (category 4). The results indicate that the use of two bioequivalent fed intestinal media from the original nine will identify in vitro the maximum and minimum solubility values for the majority of drugs and due to the media derivation this is probably applicable in vivo. When combined with a previous fasted study, this introduces interesting possibilities to measure a solubility range in vitro that can provide Quality by Design based decisions to rationalise drug and formulation development. Overall this indicates that the multi-dimensional media system is worthy of further investigation as in vitro tool to assess fed intestinal solubility.
Topics: Humans; Solubility; Hydrogen-Ion Concentration; Intestines; Pharmaceutical Preparations; Indomethacin; Intestinal Absorption
PubMed: 37890541
DOI: 10.1016/j.ejpb.2023.10.017 -
Research Square Sep 2023Prediction of high-risk events in mental disorder patients is crucial. In our previous study, we developed a deep learning model: DeepBiomarker by using electronic...
Prediction of Adverse Events Risk in Patients with Comorbid Post- Traumatic Stress Disorder and Alcohol Use Disorder Using Electronic Medical Records by Deep Learning Models.
BACKGROUND
Prediction of high-risk events in mental disorder patients is crucial. In our previous study, we developed a deep learning model: DeepBiomarker by using electronic medical records (EMR) to predict suicide related event (SRE) risk in post-traumatic stress disorder (PTSD) patients.
METHODS
We applied DeepBiomarker2 through data integration of multimodal information: lab test, medication, co-morbidities, and social determinants of health. We analyzed EMRs of 5,565 patients from University of Pittsburgh Medical Center with a diagnosis of PTSD and alcohol use disorder (AUD) on risk of developing an adverse event (opioid use disorder, SREs, depression and death).
RESULTS
DeepBiomarker2 predicted whether a PTSD + AUD patient will have a diagnosis of any adverse events (SREs, opioid use disorder, depression, death) within 3 months with area under the receiver operator curve (AUROC) of 0.94. We found piroxicam, vilazodone, dronabinol, tenofovir, suvorexant, empagliflozin, famciclovir, veramyst, amantadine, sulfasalazine, and lamivudine to have potential to reduce risk.
CONCLUSIONS
DeepBiomarker2 can predict multiple adverse event risk with high accuracy and identify potential risk and beneficial factors. Our results offer suggestions for personalized interventions in a variety of clinical and diverse populations.
PubMed: 37790550
DOI: 10.21203/rs.3.rs-3299369/v1 -
RSC Advances Sep 2023Piroxicam and naproxen are well-known non-steroidal anti-inflammatory drugs that are frequently detected in aquatic environments due to their widespread usage and...
Piroxicam and naproxen are well-known non-steroidal anti-inflammatory drugs that are frequently detected in aquatic environments due to their widespread usage and improper disposal practices. This research investigates the photocatalytic degradation of these drugs by using CeO nanoparticles. The nanoparticles were synthesized by using plant extract and were characterized through various characterization techniques such as UV-visible spectroscopy, FTIR spectroscopy, SEM, EDX, and XRD. The photocatalytic degradation of piroxicam and naproxen using CeO nanoparticles led to the efficient removal of these pharmaceutical drugs in a short time duration with photodegradation efficiencies of 89% and 97% for naproxen and piroxicam, respectively. The photodegradation reaction was found to follow pseudo-order first-order kinetics. The recyclability of the catalyst was also studied for up to six cycles where the degradation efficiency was maintained at 100% till the 2nd cycle and was decreased by 11 and 13% for piroxicam and naproxen respectively after the 6th cycle. The current work focused on the achievement of sustainable development goals (SDGs) for water purification environmentally benign nanoparticles to remedy water pollution as it is the most prevalent issue in developed and underdeveloped countries throughout the world.
PubMed: 37746332
DOI: 10.1039/d3ra04185a -
Quantum Sensing for Real-Time Monitoring of Drug Efficacy in Synovial Fluid from Arthritis Patients.Nano Letters Sep 2023Diamond-based relaxometry is a new technique that allows nanoscale magnetic resonance measurements. Here we present its first application in patient samples. More...
Diamond-based relaxometry is a new technique that allows nanoscale magnetic resonance measurements. Here we present its first application in patient samples. More specifically, we demonstrate that relaxometry can determine the free radical load in samples from arthritis patients. We found that we can clearly differentiate between osteoarthritis and rheumatoid arthritis patients in both the synovial fluid itself and cells derived from it. Furthermore, we tested how synovial fluid and its cells respond to piroxicam, a common nonsteroidal anti-inflammatory drug (NSAID). It is known that this drug leads to a reduction in reactive oxygen species production in fibroblast-like synoviocytes (FLS). Here, we investigated the formation of free radicals specifically. While FLS from osteoarthritis patients showed a drastic decrease in the free radical load, cells from rheumatoid arthritis retained a similar radical load after treatment. This offers a possible explanation for why piroxicam is more beneficial for patients with osteoarthritis than those with rheumatoid arthritis.
Topics: Humans; Synovial Fluid; Synovial Membrane; Piroxicam; Cells, Cultured; Arthritis, Rheumatoid; Osteoarthritis; Fibroblasts
PubMed: 37676737
DOI: 10.1021/acs.nanolett.3c01506 -
European Journal of Pharmaceutical... Nov 2023
PubMed: 37673750
DOI: 10.1016/j.ejps.2023.106575 -
Advanced Pharmaceutical Bulletin Jul 2023Poor aqueous solubility hampers the development of several compounds as pharmacological agents. Hence, preparing novel formulations with augmented absorption is a...
PURPOSE
Poor aqueous solubility hampers the development of several compounds as pharmacological agents. Hence, preparing novel formulations with augmented absorption is a challenge in pharmaceutical industries. In this paper, we have examined the effect of basic amino acids including arginine (ARG), lysine (LYS), and glucosamine (GlucN) on the solubility of ibuprofen (IBU) and piroxicam (PXM) as drugs with limited solubility. We have also studied the effect of the dissolution media with the pH values 1.2 to 7.4.
METHODS
The saturation shake-flask method was used for solubility studies in the presence of amino acids. Briefly, buffer solutions containing different concentrations of amino acids were prepared. Then, an excess amount of each drug with these buffers was shaken to reach equilibrium. After 48 hours, the upper phase was separated, and solubility was calculated by reading their UV-Vis absorbance.
RESULTS
The results illustrated that amino acids increased solubility of both drugs with different ratios, which were pH and concentration-dependent. Solubility improved as the amount of amino acids went up, and this upward pattern was more robust with ARG than LYS. The presence of GlucN in citrate buffer significantly enhanced IBU solubility. The solubility of PXM in accompany of GlucN in water did not change significantly while in citrate buffer solubility enhanced specially at pH 6.
CONCLUSION
Overall, GlucN in citrate buffer and ARG in phosphate buffer could be introduced as the most suitable media for IBU and PXM solubility improvement, respectively.
PubMed: 37646059
DOI: 10.34172/apb.2023.067 -
Anesthesiology and Pain Medicine Apr 2023Recently, increased attention has been paid to calcitonin for the management of osteoarthritis (OA) regarding its metabolic properties for bone turnover and cartilage.
BACKGROUND
Recently, increased attention has been paid to calcitonin for the management of osteoarthritis (OA) regarding its metabolic properties for bone turnover and cartilage.
OBJECTIVES
This study was designed to assess the efficacy of intramuscular calcitonin injection in the functional status of individuals suffering from knee OA.
METHODS
A total of 40 eligible cases with OA were randomly assigned into intervention and control groups. At baseline, pain intensity and functional ability were evaluated based on the Numeric Rating scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaires. Both groups were prescribed with AcetaGel (500 mg) and piroxicam (0.5% topical gel) every 8 hours as needed, and the patients were instructed about conservative treatments and lifestyle modifications. In the case group, the patients received calcitonin (50 IU/mL solution for injection; Aburaihan Pharmaceutical Co., Iran) intramuscularly (gluteal muscle) once a week for 4 consecutive weeks. One month after the last dose, the patients were evaluated based on NRS and WOMAC questionnaires.
RESULTS
Demographic data did not show any statistically significant difference. A total of 40 cases (male and female) with mean age values of 53.10 ± 5.28 and 54.55 ± 5.26 years were included in the case and control groups, respectively. The mean body mass index values of the case and control groups were 27.45 ± 1.57 and 27.15 ± 1.53 kg/m, respectively. After 1 month of treatment with calcitonin, significant improvements were observed in NRS outcomes (P < 0.001). The total WOMAC score was also statistically improved (P < 0.001).
CONCLUSIONS
The findings of the present study revealed that the weekly administration of 50 IU calcitonin for 28 days could significantly improve physical ability and pain intensity in OA patients.
PubMed: 37601958
DOI: 10.5812/aapm-133992 -
Cancers Aug 2023It was recently shown that targeting extracellular vimentin (eVim) is safe and effective in preclinical models. Here, we report the safety and efficacy in client-owned...
It was recently shown that targeting extracellular vimentin (eVim) is safe and effective in preclinical models. Here, we report the safety and efficacy in client-owned dogs with spontaneous bladder cancer of CVx1, an iBoost technology-based vaccine targeting eVim in combination with COX-2 inhibition. This was a single-arm prospective phase 1/2 study with CVx1 in 20 client-owned dogs with spontaneous UC which involved four subcutaneous vaccinations with CVx1 at 2-week intervals for induction of antibody titers, followed by maintenance vaccinations at 2-month intervals. Additionally, daily cyclooxygenase (COX)-2 inhibition with meloxicam was given. The response was assessed by antibody titers, physical condition, abdominal ultrasound and thorax X-ray. The primary endpoints were the development of antibody titers, as well as overall survival compared to a historical control group receiving carboplatin and COX-2 inhibition with piroxicam. Kaplan-Meier survival analysis was performed. All dogs developed antibodies against eVim. Titers were adequately maintained for the duration of this study. A median overall survival of 374 days was observed, which was 196 days for the historical control group ( < 0.01). Short-term grade 1-2 toxicity at the injection site and some related systemic symptoms peri-vaccination were observed. No toxicity was observed related to the induced antibody response. A limitation of this study is the single-arm prospective setting. CVx1 plus meloxicam consistently induced efficient antibody titers, was well tolerated and showed prolonged survival. The results obtained merit further development for human clinical care.
PubMed: 37568772
DOI: 10.3390/cancers15153958 -
International Journal of Pharmaceutics Aug 2023In nasal drug product development, screening studies are vital to select promising compounds or formulations. The Parallel Artificial Membrane Permeability Assay...
In nasal drug product development, screening studies are vital to select promising compounds or formulations. The Parallel Artificial Membrane Permeability Assay (PAMPA), a high throughput screening tool, has been applied to evaluate drug permeability across several barriers such as the skin or blood-brain barrier. Herein, a new nasal-PAMPA model was optimized to predict nasal permeability, using a biorelevant donor medium containing mucin. The apparent permeability (P) of 15 reference compounds was assessed in six different experimental conditions, and the most discriminating and predictive model was applied to a test drug (piroxicam) and mucoadhesive powder formulations loading the same drug. The model with 0.5% (w/v) mucin in the donor compartment and 2% (w/v) phosphatidylcholine in the lipid membrane accurately distinguished high and low permeable compounds. Additionally, it exhibited the highest correlation with permeation across human nasal epithelial cells, RPMI 2650 (R = 0.93). When applied to powder formulations, this model was sensitive to the presence of mucoadhesive excipients and the drug solid state. Overall, the nasal-PAMPA model was more rapid than cell-based assays, without requiring specialized training or equipment, showing to be a promising in vitro tool that can be applied in drug and formulation screening for nasal delivery.
Topics: Humans; Pharmaceutical Preparations; High-Throughput Screening Assays; Powders; Skin; Permeability; Membranes, Artificial
PubMed: 37479103
DOI: 10.1016/j.ijpharm.2023.123252 -
Frontiers in Immunology 2023COVID-19, a serious respiratory disease that has the potential to affect numerous organs, is a serious threat to the health of people around the world. The objective of...
BACKGROUND
COVID-19, a serious respiratory disease that has the potential to affect numerous organs, is a serious threat to the health of people around the world. The objective of this article is to investigate the potential biological targets and mechanisms by which SARS-CoV-2 affects benign prostatic hyperplasia (BPH) and related symptoms.
METHODS
We downloaded the COVID-19 datasets (GSE157103 and GSE166253) and the BPH datasets (GSE7307 and GSE132714) from the Gene Expression Omnibus (GEO) database. In GSE157103 and GSE7307, differentially expressed genes (DEGs) were found using the "Limma" package, and the intersection was utilized to obtain common DEGs. Further analyses followed, including those using Protein-Protein Interaction (PPI), Gene Ontology (GO) function enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Potential hub genes were screened using three machine learning methods, and they were later verified using GSE132714 and GSE166253. The CIBERSORT analysis and the identification of transcription factors, miRNAs, and drugs as candidates were among the subsequent analyses.
RESULTS
We identified 97 common DEGs from GSE157103 and GSE7307. According to the GO and KEGG analyses, the primary gene enrichment pathways were immune-related pathways. Machine learning methods were used to identify five hub genes (BIRC5, DNAJC4, DTL, LILRB2, and NDC80). They had good diagnostic properties in the training sets and were validated in the validation sets. According to CIBERSORT analysis, hub genes were closely related to CD4 memory activated of T cells, T cells regulatory and NK cells activated. The top 10 drug candidates (lucanthone, phytoestrogens, etoposide, dasatinib, piroxicam, pyrvinium, rapamycin, niclosamide, genistein, and testosterone) will also be evaluated by the value, which is expected to be helpful for the treatment of COVID-19-infected patients with BPH.
CONCLUSION
Our findings reveal common signaling pathways, possible biological targets, and promising small molecule drugs for BPH and COVID-19. This is crucial to understand the potential common pathogenic and susceptibility pathways between them.
Topics: Humans; Male; Prostatic Hyperplasia; COVID-19; SARS-CoV-2; Genes, cdc; Algorithms
PubMed: 37426635
DOI: 10.3389/fimmu.2023.1172724