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BMC Women's Health Mar 2023Primary dysmenorrhea is considered as one of the women's main problems during reproductive age. The present study aimed to investigate the effect of vitamin D on the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Primary dysmenorrhea is considered as one of the women's main problems during reproductive age. The present study aimed to investigate the effect of vitamin D on the severity of dysmenorrhea and menstrual blood loss.
METHODS
This double-blind, randomized, placebo-controlled trial, was performed on 84 single female college students between 18 and 25 years old who living in dormitories. Students with primary dysmenorrhea and vitamin D deficiency were divided into experimental (n = 42) and control (n = 42) groups. Five days before the putative beginning of their next menstrual cycle, the experimental group received 300,000 IU vitamin D (50,000 IU, two tablets every 8 h), and the control group received a placebo (oral paraffin). The effects of the supplement on the severity of dysmenorrhea and menstrual blood loss were evaluated one cycle before and during two successive cycles. Using the visual analog scale (VAS), verbal multidimensional scoring system (VMS), and pictorial blood assessment chart (PBLAC) questionnaires. Fisher's exact, Chi-square, independent sample t-test and repeated measurements were used.
RESULTS
In total, 78 of the 84 students completed the study (39 students per group). The intervention resulted in a significant reduction in the mean scores of both the VAS and VMS in the experimental group, in the first and second menstrual cycles (p < 0.001, p < 0.001, respectively), but not in the means score of PBLAC. Mefenamic acid consumption at the first and second menstruation period, in the experimental group was lower than the control group (p = 0.009, p < 0.001, respectively).
CONCLUSIONS
The results indicate that vitamin D supplementation could decrease the severity of primary dysmenorrhea and the need to consume pain-relief medications. Contrariwise vitamin D supplementation had no significant effect on menstrual blood loss.
TRIAL REGISTRATION
This trial was registered in the Iranian Registry of Clinical Trials with code IRCT201305212324N on 18/1/2014. URL of registry: https://en.irct.ir/trial/1964 .
Topics: Female; Humans; Adolescent; Young Adult; Adult; Dysmenorrhea; Menstruation; Vitamin D; Iran; Mefenamic Acid; Hemorrhage
PubMed: 36973702
DOI: 10.1186/s12905-023-02284-5 -
European Journal of Pharmaceutics and... May 2023For solid oral dosage forms drug solubility in intestinal fluid is an important parameter influencing product performance and bioavailability. Solubility along with...
For solid oral dosage forms drug solubility in intestinal fluid is an important parameter influencing product performance and bioavailability. Solubility along with permeability are the two parameters applied in the Biopharmaceutics and Developability Classification Systems (DCS) to assess a drug's potential for oral administration. Intestinal solubility varies with the intestinal contents and the differences between the fasted and fed states are recognised to influence solubility and bioavailability. In this study a novel fed state simulated media system comprising of nine media has been utilised to measure the solubility of seven drugs (ibuprofen, mefenamic acid, furosemide, dipyridamole, griseofulvin, paracetamol and acyclovir) previously studied in the fasted state DCS. The results demonstrate that the fed nine media system provides a range of solubility values for each drug and solubility behaviour is consistent with published design of experiment studies conducted in either the fed or fasted state. Three drugs (griseofulvin, paracetamol and acyclovir) exhibit very narrow solubility distributions, a result that matches published behaviour in the fasted state, indicating that this property is not influenced by the concentration of simulated media components. The nine solubility values for each drug can be utilised to calculate a dose/solubility volume ratio to visualise the drug's position on the DCS grid. Due to the derivation of the nine media compositions the range and catergorisation could be considered as bioequivalent and can be combined with the data from the original fed intestinal fluid analysis to provide a population based solubility distribution. This provides further information on the drugs solubility behaviour and could be applied to quality by design formulation approaches. Comparison of the fed results in this study with similar published fasted results highlight that some differences detected match in vivo behaviour in food effect studies. This indicates that a combination of the fed and fasted systems may be a useful in vitro biopharmaceutical performance tool. However, it should be noted that the fed media recipes in this study are based on a liquid meal (Ensure Plus) and this may not be representative of alternative fed states achieved through ingestion of a solid meal. Nevertheless, this novel approach provides greater in vitro detail with respect to possible in vivo biopharmaceutical performance, an improved ability to apply risk-based approaches and the potential to investigate solubility based food effects. The system is therefore worthy of further investigation but studies will be required to expand the number of drugs measured and link the in vitro measurements to in vivo results.
Topics: Humans; Solubility; Acetaminophen; Griseofulvin; Pharmaceutical Preparations; Intestines; Administration, Oral; Intestinal Absorption
PubMed: 36934829
DOI: 10.1016/j.ejpb.2023.03.005 -
Materials (Basel, Switzerland) Feb 2023In this work, we studied conformational equilibria of molecules of mefenamic acid in its diluted solution in scCO under isochoric heating conditions in the temperature...
In this work, we studied conformational equilibria of molecules of mefenamic acid in its diluted solution in scCO under isochoric heating conditions in the temperature range of 140-210 °C along the isochore corresponding to the scCO density of 1.1 of its critical value. This phase diagram range totally covers the region of conformational transitions of molecules of mefenamic acid in its saturated solution in scCO. We found that in the considered phase diagram region, the equilibrium of two conformers is realized in this solution. In the temperature range of 140-180 °C, conformer I related to the first, most stable polymorph of mefenamic acid prevails. In the temperature range of 200-210 °C, conformer II, which is related to the second metastable polymorph becomes dominant. Based on the results of quantum chemical calculations and experimental IR spectroscopy data on the mefenamic acid conformer populations, we classified this temperature-induced conformational crossover as an entropy-driven phenomenon.
PubMed: 36837033
DOI: 10.3390/ma16041403 -
International Journal of Biological... Apr 2023SARS-CoV-2 Main protease (M) is a well-known drug target against SARS-CoV-2 infection. Identification of M inhibitors is vigorously pursued due to its crucial role in...
SARS-CoV-2 Main protease (M) is a well-known drug target against SARS-CoV-2 infection. Identification of M inhibitors is vigorously pursued due to its crucial role in viral replication. The present study was aimed to identify M inhibitors via repurposing of US-FDA approved drugs by STD-NMR spectroscopy. In this study, 156 drugs and natural compounds were evaluated against M. Among them, 10 drugs were found to be interacting with M, including diltiazem HCl (1), mefenamic acid (2), losartan potassium (3), mexiletine HCl (4), glaucine HBr (5), trimebutine maleate (6), flurbiprofen (7), amantadine HCl (8), dextromethorphan (9), and lobeline HCl (10) in STD-NMR spectroscopy. Their interactions were compared with three standards (Repurposed anti-viral drugs), dexamethasone, chloroquine phosphate, and remdesivir. Thermal stability of M and dissociation constant (K) of six interacting drugs were also determined using DSF. RMSD plots in MD simulation studies showed the formation of stable protein-ligand complexes. They were further examined for their antiviral activity by plaque reduction assay against SARS-CoV-2, which showed 55-100% reduction in viral plaques. This study demonstrates the importance of drug repurposing against emerging and neglected diseases. This study also exhibits successful application of STD-NMR spectroscopy combined with plaque reduction assay in rapid identification of potential anti-viral agents.
Topics: Humans; Antiviral Agents; COVID-19; SARS-CoV-2; Drug Repositioning; Protease Inhibitors; Molecular Docking Simulation; Molecular Dynamics Simulation
PubMed: 36740128
DOI: 10.1016/j.ijbiomac.2023.123540 -
JNMA; Journal of the Nepal Medical... Dec 2022Primary dysmenorrhea is painful menstruation in women with normal pelvic anatomy, usually beginning during adolescence, primarily associated with a normal ovulatory...
INTRODUCTION
Primary dysmenorrhea is painful menstruation in women with normal pelvic anatomy, usually beginning during adolescence, primarily associated with a normal ovulatory cycle. There is an increased likelihood of self-medication among medical students. The aim of this study is to find out the prevalence of self-medication in primary dysmenorrhea among undergraduate students in a medical college.
METHODS
A descriptive cross-sectional study was conducted in a medical college among undergraduate female students with primary dysmenorrhea from 1 February 2022 to 31 May 2022. Ethical approval was obtained from the Institutional Review Committee of the same institute (Reference number: 254/2021). Convenience sampling was done. Data were collected through a self-administered questionnaire. Point estimate and 95% Confidence Interval were calculated.
RESULTS
Among 213 students with primary dysmenorrhea, self-medication was found to be in 78 (36.62%) (30.15-43.09, 95% Confidence Interval)). Among all the self-medications used, mefenamic acid was most common, used by 45 (57.69%) students, followed by paracetamol 11 (14.10%).
CONCLUSIONS
The prevalence of self-medication practice in primary dysmenorrhea among undergraduate students was lower when compared to similar studies done in similar settings.
KEYWORDS
dysmenorrhea; menstruation; prevalence; self medication.
Topics: Adolescent; Female; Humans; Self Medication; Dysmenorrhea; Cross-Sectional Studies; Students, Medical; Surveys and Questionnaires; Prevalence
PubMed: 36705107
DOI: 10.31729/jnma.7816 -
Frontiers in Bioengineering and... 2022The purpose of the study was to devise the superporous hydrogels (SPHs) of mefenamic acid (MA) to acquire the sustained action of the MA in the body. The superporous...
The purpose of the study was to devise the superporous hydrogels (SPHs) of mefenamic acid (MA) to acquire the sustained action of the MA in the body. The superporous hydrogels of mefenamic acid were formulated by employing the gas blowing method. The central composite rotatable design (CCRD) was applied to optimize the effect of independent formulation factors like acrylic acid (AC), HPMC and glycerol (GLY) over dependent variables like porosity, viscosity, drug content and swelling ratio of superporous hydrogels in water, phosphate buffer (pH 6.8) and in 0.1N HCl (pH 1.2). A number of characteristics such as void fraction, surface morphology by Scanning electron microscopy (SEM) and drug release study were governed along with physico-chemical analysis by Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and appraised statistically by employing the ANOVA. The comparative analgesic activity of optimized superporous hydrogel formulation SPH17 was also analyzed by using tail flick method. The Fourier transform infrared spectroscopy and Differential scanning calorimetry studies approved the physical compatibility between the polymers and the drug. The Scanning electron microscopy study specified micrographic insight about the structure of formed formulations comprising presence of pores, fibers and drug-hole aggregates. The superporous hydrogels were detected to be low dense as they expressed density lower than 0.75 g/cc. The decrease in concentration of the polymers and cross linker contributed towards the increase in the void fraction of the superporous hydrogel formulations. The optimized formulation SPH 17 exhibited a highly sustained release of MA for up to 10 h in the both 0.1 N HCl and phosphate buffer (66.6%) media. The non-fickian release of drug revealed the coupling of the diffusion and polymer relaxation mechanism of the drug release from the formulations. The obtained outcomes suggested that analgesic effect of SPH 17 was significantly ( < 0.05) higher than that of simple suspension of mefenamic acid and total analgesic effect duration for superporous hydrogel was also doubled as compared to the duration of analgesic effect produced by drug suspension. The successfully formulated SPH with HPMC K100M as a gelling agent had sustained the action of the mefenamic acid (MF) by improving its poor solubility and permeability. The introduction of inter-penetrating polymeric network (acrylic acid) using glycerol as a cross linker impart increased residence time to superporous hydrogels which ultimately enhanced the feasibility of using superporous hydrogel as oral sustained release devices particularly for gastric retention.
PubMed: 36588944
DOI: 10.3389/fbioe.2022.1057627 -
Organic Process Research & Development Dec 2022To facilitate integrated end-to-end pharmaceutical manufacturing using digital design, a model capable of transferring material property information between operations... (Review)
Review
To facilitate integrated end-to-end pharmaceutical manufacturing using digital design, a model capable of transferring material property information between operations to predict product attributes in integrated purification processes has been developed. The focus of the work reported here combines filtration and washing operations used in active pharmaceutical ingredient (API) purification and isolation to predict isolation performance without the need of extensive experimental work. A fixed Carman-Kozeny filtration model is integrated with several washing mechanisms (displacement, dilution, and axial dispersion). Two limiting cases are considered: case 1 where there is no change in the solid phase during isolation (no particle dissolution and/or growth), and case 2 where the liquid and solid phases are equilibrated over the course of isolation. In reality, all actual manufacturing conditions would be bracketed by these two limiting cases, so consideration of these two scenarios provides rigorous theoretical bounds for assessing isolation performance. This modeling approach aims to facilitate the selection of most appropriate models suitable for different isolation scenarios, without the requirement to use overly complex models for straightforward isolation processes. Mefenamic acid and paracetamol were selected as representative model compounds to assess a range of isolation scenarios. In each case, the objective of the models was to identify the purity of the product reached with a fixed wash ratio and minimize the changes to the crystalline particle attributes that occur during the isolation process. This was undertaken with the aim of identifying suitable criteria for the selection of appropriate filtration and washing models corresponding to relevant processing conditions, and ultimately developing guidelines for the digital design of filtration and washing processes.
PubMed: 36569418
DOI: 10.1021/acs.oprd.2c00165 -
Journal of Advanced Pharmaceutical... 2022This study determined the efficacy of extract of the stem bark of (ESBLc) on histopathology and inflammatory cell infiltration in the gastric of rats induced by...
This study determined the efficacy of extract of the stem bark of (ESBLc) on histopathology and inflammatory cell infiltration in the gastric of rats induced by mefenamic acid. We grouped 20 rats into 5; Group 1 (positive control, mefenamic acid + sucralfate suspension), Group 2 (negative control, mefenamic acid), Group 3 (mefenamic acid + ESBLc 1575 mg/kg), Group 4 (mefenamic acid + ESBLc 3150 mg/kg), and Group 5 (mefenamic acid + ESBLc 3600 mg/kg). The dose of mefenamic acid used was 23.25 mg/kg, given orally for 7 days. Gastric histopathological observations were carried out qualitatively, and inflammatory cell infiltration was analyzed quantitatively by one-ay ANOVA. The qualitative and quantitative analysis results showed that ESBLc had efficacy in restoring damaged gastric tissue of rats; statistically, 3150 mg/kg and 6300 mg/kg effectively reduced inflammatory cell infiltration. ESBLc recovered the function of gastric organs of induced by mefenamic acid, including improved mucosa and reduced inflammatory cell infiltration in the gastric. The doses of ESBLc, which effectively reduced inflammatory cell infiltrations, were 3150 mg/kg and 6300 mg/kg BW.
PubMed: 36568053
DOI: 10.4103/japtr.japtr_475_22 -
Pharmaceutical Research Dec 2022Particle shape can have a significant impact on the bulk properties of materials. This study describes the development and application of machine-learning models to...
OBJECTIVE
Particle shape can have a significant impact on the bulk properties of materials. This study describes the development and application of machine-learning models to predict the crystal shape of mefenamic acid recrystallized from organic solvents.
METHODS
Crystals were grown in 30 different solvents to establish a dataset comprising solvent molecular descriptors, process conditions and crystal shape. Random forest classification models were trained on this data and assessed for prediction accuracy.
RESULTS
The highest prediction accuracy of crystal shape was 93.5% assessed by fourfold cross-validation. When solvents were sequentially excluded from the training data, 32 out of 84 models predicted the shape of mefenamic acid crystals for the excluded solvent with 100% accuracy and a further 21 models had prediction accuracies from 50-100%. Reducing the feature set to only solvent physical property descriptors and supersaturations resulted in higher overall prediction accuracies than the models trained using all available or another selected subset of molecular descriptors. For the 8 solvents on which the models performed poorly (< 50% accuracy), further characterisation of crystals grown in these solvents resulted in the discovery of a new mefenamic acid solvate whereas all other crystals were the previously known form I.
CONCLUSIONS
Random forest classification models using solvent physical property descriptors can reliably predict crystal morphologies for mefenamic acid crystals grown in 20 out of the 28 solvents included in this work. Poor prediction accuracies for the remaining 8 solvents indicate that further factors will be required in the feature set to provide a more generalized predictive morphology model.
Topics: Mefenamic Acid; Random Forest; Solvents; Machine Learning
PubMed: 36534313
DOI: 10.1007/s11095-022-03450-4 -
Medical treatment for heavy menstrual bleeding in primary care: 10-year data from the ECLIPSE trial.The British Journal of General Practice... Dec 2022Heavy menstrual bleeding (HMB) is a common problem that can significantly affect women's lives. There is a lack of evidence on long-term outcomes after seeking treatment. (Observational Study)
Observational Study
BACKGROUND
Heavy menstrual bleeding (HMB) is a common problem that can significantly affect women's lives. There is a lack of evidence on long-term outcomes after seeking treatment.
AIM
To assess continuation rates of medical treatments and rates of surgery in women 10 years after initial management for HMB in primary care.
DESIGN AND SETTING
This was a prospective observational cohort study.
METHOD
Women with HMB who participated in the ECLIPSE primary care trial (ISRCTN86566246) completed questionnaires 10 years after randomisation to the levonorgestrel-releasing intrauterine system (LNG-IUS) or other usual medical treatments (oral tranexamic acid, mefenamic acid, combined oestrogen-progestogen; or progesterone alone). Outcomes were rates of surgery, medical treatments, and quality of life using the 36-item Short-Form Health Survey (SF-36) and EuroQoL EQ-5D.
RESULTS
The responding cohort of 206 women was demographically and clinically representative of the original trial population. Mean age at baseline was 41.9 years (SD 4.9) and 53.7 years (SD 5.1) at follow-up. Over the 10-year follow-up, 60 of 206 (29.1%) women had surgery (hysterectomy = 34, 16.5%; endometrial ablation = 26, 12.6%). Between 5 and 10 years, 89 women (43.2%) ceased all medical treatments and 88 (42.7%) used LNG-IUS alone or in combination with other treatments. Fifty-six women (27.2%) were using LNG-IUS at 10 years. There were improvements over time in quality-of-life scores, with no evidence of differences in these or other outcomes between the two groups.
CONCLUSION
Medical treatments for women with HMB can be successfully initiated in primary care, with low rates of surgery and improvement in quality of life observed a decade later.
Topics: Female; Humans; Male; Menorrhagia; Intrauterine Devices, Medicated; Levonorgestrel; Quality of Life; Prospective Studies; Primary Health Care
PubMed: 36376071
DOI: 10.3399/bjgp.2022.0260