Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24.052
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-36411081

RESUMO

BACKGROUND AND OBJECTIVES: Cladribine tablets cause a reduction in lymphocytes with a predominant effect on B-cell and T-cell counts. The MAGNIFY-MS substudy reports the dynamic changes on multiple peripheral blood mononuclear cell (PBMC) subtypes and immunoglobulin (Ig) levels over 12 months after the first course of cladribine tablets in patients with highly active relapsing multiple sclerosis (MS). METHODS: Immunophenotyping was performed at baseline (predose) and at the end of months 1, 2, 3, 6, and 12 after initiating treatment with cladribine tablets. Assessments included lymphocyte subtype counts of CD19+ B cells, CD4+ and CD8+ T cells, CD16+ natural killer cells, plasmablasts, and Igs. Immune cell subtypes were analyzed by flow cytometry, and serum IgG and IgM were analyzed by nephelometric assay. Absolute cell counts and percentage change from baseline were assessed. RESULTS: The full analysis set included 57 patients. Rapid reductions in median CD19+, CD20+, memory, activated, and naive B-cell counts were detected, reaching nadir by month 2. Thereafter, total CD19+, CD20+, and naive B-cell counts subsequently reconstituted, but memory B cells remained reduced by 93%-87% for the remainder of the study. The decrease in plasmablasts was slower, reaching nadir at month 3. Decrease in T-cell subtypes was also slower and more moderate compared with B-cell subtypes, reaching nadir between months 3 and 6. IgG and IgM levels remained within the normal range over the 12-month study period. DISCUSSION: Cladribine tablets induce a specific pattern of early and sustained PBMC subtype dynamics in the absence of relevant Ig changes: While total B cells were reduced dramatically, T cells were affected significantly less. Naive B cells recovered toward baseline, naive CD4 and CD8 T cells did not, and memory B cells remained reduced. The results help to explain the unique immune depletion and repopulation architecture regarding onset of action and durability of effects of cladribine tablets while largely maintaining immune competence. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03364036. Date registered: December 06, 2017.


Assuntos
Cladribina , Esclerose Múltipla , Humanos , Cladribina/farmacologia , Leucócitos Mononucleares , Linfócitos T CD8-Positivos , Esclerose Múltipla/tratamento farmacológico , Comprimidos , Antígenos CD20 , Antígenos CD19 , Imunoglobulina G , Imunoglobulina M
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121919, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36179566

RESUMO

New simple sensitive and reliable spectrofluorimetric approach was established for the determination of the antidiabetic drug; Alogliptin (ALG) in its pure and tablet forms. The developed approach is depended on the suppressive action of ALG on the eosin Y native fluorescence. The quenching action of ALG on the eosin Y native fluorescence was measured at acidic medium pH: 3.5, emission wavelength 541 nm (λex. 260 nm). The relative fluorescence intensity (RFI) was measured, and it was directly proportional to ALG concentration in the concentration range of (15-110) µg/mL. The developed and optimized approach was entirely validated regarding to ICH guidelines. The developed method application was successfully extended for ALG content uniformity test (CU). The distribution fraction (DF), rate constants (K), and free energy changes (ΔG°) were calculated. The results obtained were compared to that of the published spectrophotometric one.


Assuntos
Corantes Fluorescentes , Amarelo de Eosina-(YS) , Espectrometria de Fluorescência/métodos , Comprimidos
3.
Food Chem ; 402: 134206, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36162173

RESUMO

Isolated from milk, lactose is a food ingredient and an excipient in medicines. Its chiral forms are known to undergo epimerisation in solution but understanding whether this chemical reaction occurs in lactose powders exposed to tropical environments is of great importance for medicine stability and food quality. Thus, the aim of this study was to investigate epimerisation within lactose powders stored under specified conditions that model hot and humid climates. Powdered α-lactose monohydrate was stable under all conditions, whereas ß-lactose stored at 40 °C and 75 % RH suffered epimerisation, falling to 3.9 ± 0.3 ß-content after 6-months. Zero-order kinetics observed by NMR, indicated a shelf-life (5 % degradation) of 4.55-days for ß-lactose containing powders. Thermal analysis revealed monohydrate formation as ß-lactose epimerised, seen as tomahawk shaped α-lactose monohydrate crystals by SEM. Therefore, it is recommended ß-rich lactose containing powders, e.g., infant formula or direct compression tablet formulations, are stored hermetically in tropical zones.


Assuntos
Ingredientes de Alimentos , Lactose , Humanos , Animais , Lactose/química , Pós/química , Excipientes/química , Leite , Comprimidos
4.
J Pharm Biomed Anal ; 222: 115066, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36191442

RESUMO

In recent years, nitrosamines have been discovered in some types of drug products that becomes a current regulatory hotspot, and have attracted a lot attention from both regulatory authorities and industry. This manuscript provided an industry perspective on the nitrosamines research. A liquid chromatography coupled with tandem mass spectrometry(LC-MS/MS)method was developed and applied for the quantification of N-nitrosodimethylamine (NDMA) in metformin hydrochloride sustained-release tablets (MET). The key factors resulting in the NDMA formation in MET were identified through forced degradation and drug-excipient studies, which included high temperature, dimethylamine, strong alkali and oxidation conditions, peroxide and alkaline components contained in the formulation as well as the nitrite and nitrate impurities that might be presented in certain excipients. Further, API particle size and water content of the drug product would also affect the growth rate of NDMA. Therefore, the following mitigation strategies to reduce the risk of nitrosamines in the finished drug product are proposed in this manuscript: 1) avoid the use of excipients containing nitrite, nitrate and peroxide impurities; 2) avoid high temperature and strong alkaline environment in the production and storage condition; 3) maintain an appropriate water content level in the formulation. Based on the above principles, it was recommended to add antioxidant or incorporate excipient such as Na2CO3 to modify the formulation pH to weak basic environment in the formulation of MET, which can could effectively prevent formation of NDMA in the stability process.


Assuntos
Metformina , Nitrosaminas , Dimetilnitrosamina/química , Derivados da Hipromelose , Excipientes/análise , Cromatografia Líquida , Nitritos , Preparações de Ação Retardada , Nitratos , Espectrometria de Massas em Tandem , Nitrosaminas/química , Comprimidos , Peróxidos , Água
5.
J Pharm Biomed Anal ; 222: 115106, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36283324

RESUMO

From the seed of Aesculus hippocastanum L., a complex mixture of triterpene saponin glycosides known as aescin was isolated, purified and characterized to be an active pharmaceutical ingredient for preparing of drug products. A reversed phase high performance liquid chromatographic method with UV detection was developed for the determination of total triterpene glycosides in enteric coated tablets containing aescin in a pattern-oriented manner. The mobile phase consisted of a mixture of acetonitrile and 0.1 % phosphoric acid solution (40: 60). UV detection was performed at 220 nm. The chromatographic column was Gemini C18 column, 5 µm 250 mm × 4.6 mm, which was maintained at 25 ◦C, connected with a precolumn (C18, 4.0 × 3.0 mm, 5 µm). The linear range was from 53.4 to 160.1 µg·mL-1. The RSD of intra-and inter-day precision variations were less than 1 % and the mean recovery was (100.66 ± 0.49) % (RSD = 0.64 %). The method showed its suitability, simplicity, rapidity and precision. Accordingly, it was proven adequate for quality control of this herbal drug product either for registration with the regulartory authority or routine analysis.


Assuntos
Aesculus , Escina , Cromatografia Líquida de Alta Pressão/métodos , Escina/análise , Aesculus/química , Comprimidos com Revestimento Entérico , Comprimidos/análise , Controle de Qualidade
6.
Talanta ; 251: 123812, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35961083

RESUMO

This study describes the development of electrochemical paper-based analytical devices (ePADs) using carbon-based paste combining silicone glue and graphite powder. The ePADs were manufactured using the screen-printing technique, which consisted of depositing the conductive ink on a screencast on the paper surface. In addition, an alternative electrical connector was designed and 3D-printed to make the detection method cheaper, portable and reproducible. The morphological, structural, and electrochemical properties of the conductive material developed were investigated through scanning electron microscopy (SEM), Raman spectroscopy, electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV) measurements. The ePADs combined with the alternative connector revealed high repeatability, reproducibility, and stable responses considering a well-known redox probe ([Fe(CN)6]4-/3-). In addition, the proposed ePAD provided a linear response for standard solutions of ascorbic acid (AA) in the concentration range between 0.1 and 2.0 mmol L-1. The achieved limit of detection was 4.0 µmol L-1. As proof of applicability, the ePADs were evaluated for AA analysis in synthetic biofluids (blood plasma and urine), vitamin C tablets, and food (gelatine and orange juice) samples. The analytical parameters of the proposed device were compared with other reports in the literature and exhibited similar or even superior performance, highlighting its feasibility for sensing applications.


Assuntos
Grafite , Ácido Ascórbico , Carbono/química , Técnicas Eletroquímicas/métodos , Eletrodos , Grafite/química , Tinta , Pós , Reprodutibilidade dos Testes , Silicones , Comprimidos
7.
Clin Pharmacol Drug Dev ; 11(2): 165-172, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34453416

RESUMO

Tadalafil is an effective, reversible, and competitive phosphodiesterase 5 inhibitor mainly used to treat erectile dysfunction. This study investigated the bioequivalence of generic and marketed formulations of 10-mg tadalafil tablets under fasted and fed conditions. This open-label, randomized, single-dose, 2-period crossover study included 53 healthy Chinese men (aged 20-43 years). Plasma samples were collected from 0.5 hours before treatment to 72 hours after each dose and analyzed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety assessments were performed throughout the study. For the fasted state, the 90% confidence intervals of the geometric mean ratios between the generic and marketed formulations were 86.1% to 99.1% for the maximum plasma concentration and 88.4% to 100.3% for the area under the plasma concentration-time curve from time 0 to infinity, and the corresponding values under the fed state were and 99.9% to 108.4% and 95.7% to 104.3%, respectively. All data were within the accepted bioequivalence range of 80% to 125%. After consuming high-fat, high-calorie meals in the fed condition, the time to the maximum plasma concentration was similar between the formulations, and area under the plasma concentration-time curve from time 0 to infinity and maximum plasma concentration were 10.2% and 6.55% higher, respectively, for the marketed formulation. Thus, food had no clinically relevant effect on tadalafil exposure following a single oral dose in healthy Chinese men. No serious adverse reactions were reported. These results indicated that the analyzed generic and marketed tadalafil tablets were bioequivalent with similar safety profiles.


Assuntos
Jejum , Adulto , China , Estudos Cross-Over , Humanos , Masculino , Comprimidos , Tadalafila/efeitos adversos , Equivalência Terapêutica , Adulto Jovem
8.
ScientificWorldJournal ; 2022: 7924600, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408195

RESUMO

The proliferation of counterfeit and poor-quality drugs is a major public health problem, especially in developing countries such as Ghana where there are inadequate resources to effectively monitor their prevalence. Most of these drugs, which are counterfeited, are drugs, which are in high demand and will reap huge profits for the unscrupulous people who engage in such activities. The introduction of Omeprazole as one of the first-line therapies in the management of peptic and duodenal ulcers in the treatment guidelines of Ghana has resulted in many generics being introduced onto the market. The pharmaceutical quality of fifteen randomly sampled Omeprazole capsule brands in the Kumasi metropolis was assessed using the innovator brand as a comparator to confirm their suitability for patient use and to provide data for drug regulatory agencies in Ghana concerning poor quality omeprazole brands. All the sampled brands complied with the official specifications for identification with good primary and secondary packaging characteristics. Ninety-four (94%) of the sampled brands passed the uniformity of weight test. All the brands (n = 16) representing 100% passed the disintegration tests. Sixty percent (60%) of the sampled brands passed the drug content test. Ten brands (66.7%) met the specification for in vitro dissolution test. From f2 analysis, the dissolution profiles of only five brands (31%) were similar to that of the reference brand which indicated that they could be used interchangeably in clinical practice. Conclusively, ten out of the fifteen sampled brands were of good quality and only five could be used as a substitute for the innovator. Thus, regulatory agencies will need to strengthen their postmarket surveillance to ensure that generic brands of good quality are allowed onto the market.


Assuntos
Omeprazol , Humanos , Comprimidos , Cápsulas/química , Controle de Qualidade , Gana
9.
AAPS J ; 25(1): 1, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36396889

RESUMO

In vitro dissolution generally involves sink conditions, so dissolution equations generally do not need to accommodate non-sink conditions. Greater use of biorelevant media, which are typically less able to provide sink conditions than pharmaceutical surfactants, necessitates equations that accommodate non-sink conditions. One objective was to derive an integrated, one-parameter dissolution equation for percent dissolved versus time that accommodates non-sink effects via drug solubility and dissolution volume parameters, including incomplete solubility. A second objective was to characterize the novel equation by fitting it to biorelevant dissolution profiles of tablets of two poorly water-soluble drugs, as well as by conducting simulations of the effect of dose on dissolution profile. The Polli dissolution equation was derived, [Formula: see text], where M0 is the drug dose (mg), cs is drug solubility (mg/ml), V is dissolution volume (ml), and kd is dissolution rate coefficient (ml/mg per min). Maximum allowable percent dissolved was determined by drug solubility and not a fitted extent of dissolution parameter. The equation fit tablet profiles in the presence and absence of sink conditions, using a single fitted parameter, kd, and where solubility ranged over a 1000-fold range. kd was generally smaller when cs was larger. FeSSGF provided relatively small kd values, reflecting FeSSGF colloids are large and slowly diffusing. Simulations showed impact of non-sink conditions, as well as plausible kd values for various cs scenarios, in agreement with observed kd values. The equation has advantages over first-order and z-factor dissolution rate equations. An Excel file for regression is provided.


Assuntos
Tensoativos , Solubilidade , Comprimidos , Difusão
10.
J Mater Chem B ; 10(45): 9457-9465, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36346268

RESUMO

The development and progression of colorectal cancer (CRC) are highly dependent on the long-term inflammatory microenvironment with immune dysregulation in the colorectum. However, effective therapeutics are limited to targeting CRC. Here, we developed oral fullerene tablets (OFTs) that can act directly on the colorectal site by oral administration and reduce the inflammatory state at the tumor site for effective CRC therapy. In detail, OFTs scavenged reactive oxygen species (ROS), restrained the mutation of the wild-type P53, inhibited the activation of the inflammatory pathway nuclear factor-κB (NF-κB) and the signal transducer and activator of transcription 3 (STAT3) in the colorectum of CRC mice. Subsequently, OFTs could greatly reduce the infiltration of pro-inflammatory M1 macrophages and neutrophils at the tumor site, restoring the inflammatory microenvironment and immune homeostasis in the colorectal region, and ultimately achieving the inhibition of CRC. In addition, there were no significant toxic side effects of the long-term administration of OFTs. Our work provides an effective oral therapeutic strategy for CRC therapy by modulating the colorectal tumor inflammatory microenvironment and sheds light on the route for oral nano-materials in the clinical treatment of CRC.


Assuntos
Neoplasias Colorretais , Fulerenos , Camundongos , Animais , Fulerenos/farmacologia , Fulerenos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Transdução de Sinais , NF-kappa B/metabolismo , Comprimidos , Microambiente Tumoral
11.
Medicine (Baltimore) ; 101(46): e31664, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401442

RESUMO

BACKGROUND: Meta-analysis was used to evaluate the efficacy of Fufang Biejia Ruangan Tablets in the treatment of chronic hepatitis B (CHB) liver fibrosis. METHODS: Databases, including PubMed, China Knowledge Network (CNKI), China Biomedical Database (CBM), Wan Fang, VIP database, Embase, and Cochrane Library were searched. The time was searched up to May 2022. The participant intervention comparator outcomes of this study were as follows: P, patients with CHB liver fibrosis; I, Fufang Biejia Ruangan Tablets; C, pharmacological placebo; O, the efficacy rate, alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), procollagen III protein (PIIIP), hyaluronic acid (HA), laminin (LN), collagen C type IV (IV-C), portal vein diameter, spleen thickness and HBV-DNA negative conversion rate. The Cochrane Risk of Bias tool, Begg's test and Egger's test were used to evaluate the methodological quality of eligible studies. A randomized controlled trial of Fufang Biejia Ruangan Tablets was used to treat CHB liver fibrosis. Three reviewers independently selected trials, extracted data, cross-checked, and performed methodological quality assessments. Data analysis was completed by Review Manager 5.3. RESULTS: Twenty-six studies with 2717 patients were included in the meta-analysis. The meta-analysis showed that Fufang Biejia Ruangan Tablets was effective by increasing the efficacy. Fufang Biejia Ruangan Tablets was more efficient in improving ALT, AST, TBIL, ALB, PIIIP, HA, LN, IV-C, portal vein diameter, spleen thickness, and HBV-DNA negative conversion rate with no serious adverse reactions. CONCLUSION: It was shown that Fufang Biejia Ruangan Tablets can effectively improve liver function and relieve liver fibrosis, but future research should focus on rigorously designed, multicenter, and large randomized controlled trials.


Assuntos
Hepatite B Crônica , Humanos , Hepatite B Crônica/tratamento farmacológico , DNA Viral , Cirrose Hepática/tratamento farmacológico , Alanina Transaminase , Comprimidos , Adjuvantes Farmacêuticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
12.
Molecules ; 27(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36364175

RESUMO

In the present work, a two-dimensional qNMR method for the determination of sennosides was established. Using band-selective HSQC and the cross correlations of the characteristic 10-10' bonds, we quantified the total amount of the value-determining dianthranoids in five minutes, thus, rendering the method not only fast, but also specific and stability indicating. The validation of the method revealed excellent accuracy (recovery rates of 98.5 to 103%), precision (RSD values of 3.1%), and repeatability (2.2%) and demonstrated the potential of 2D qNMR in the quality control of medicinal plants. In a second method, the use of 2D qNMR for the single analysis of sennosides A, B, and A1 was evaluated with acceptable measurement times (31 min), accuracy (93.8%), and repeatability (5.4% and 5.6%) for the two major purgatives sennoside A and B. However, the precision for sennoside B and A1 was not satisfactory, mainly due to the low resolution of the HSQC signals of the two compounds.


Assuntos
Extrato de Senna , Senna (Planta) , Senosídeos , Extrato de Senna/química , Senna (Planta)/química , Catárticos , Comprimidos , Antraquinonas/análise
13.
Molecules ; 27(21)2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36364443

RESUMO

Stability-indicating methods are awesome tools to ensure the safety and efficacy of active pharmaceutical ingredients (APIs). An accurate comparative study involving the use of potentiometric sensors for the determination of bromazepam (BRZ) in the presence of its main product of degradation and impurity was performed by the fabrication of two membrane electrodes. A screen-printed electrode (SPE) and a solid-contact glassy carbon electrode (SCE) were fabricated and their performance optimized. The fabricated sensors showed a linear electrochemical response in the concentration range 1.0 × 10-6 M to 1.0 × 10-2 M. The electrodes exhibited Nernstian slopes of 59.70 mV/decade and 58.10 mV/decade for the BRZ-SPE and BRZ-SCE membrane electrodes, respectively. The electrochemical performance was greatly affected by the medium pH. They showed an almost ideal electrochemical performance between pH 3.0 and pH 6.0. The fabricated membranes were applied successfully for the quantification of BRZ in the presence of up to 90% of its degradation product. Moreover, a successful application of the fabricated electrodes was performed for the sensitive and selective quantification of BRZ in its tablet form without any pretreatment procedure.


Assuntos
Bromazepam , Eletrodos , Potenciometria , Carbono , Comprimidos
14.
Arerugi ; 71(9): 1122-1128, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36372423

RESUMO

BACKGROUND: We examined the clinical effects of Cedarcure® tablets for sublingual immunotherapy (SLIT), and examined the enhancement of the effects over the years of treatment. METHODS: The subjects were 358 patients who treated with SLIT (126 of third year of treatment, 102 of second year, 130 of first year) in a single clinic. The clinical efficacy was evaluated with visual analog scale (VAS) of nose, eye and total symptoms during the peak season of moderate amount of pollen dispersal (2485 grains/cm2/season) in 2022. Concomitant medication scores were calculated by Japanese guidelines. Because many cases of combined use of mite SLIT (dual SLIT) were included in the subjects, we compared cedar SLIT alone and dual SLIT as a secondary analysis. RESULTS: Clinical efficacy improved with the years of treatment, and all assessments of VAS in the 3rd year were significantly better than in the 1st year of treatment (p<0.01). The third year was better with sneezing and nasal discharge than the 2nd year, and the 2nd year was better with itchy eyes than the 1st year (p<0.05). Drug scores were also lower in the 3rd and 2nd years than in the 1st year (p<0.05). Additional mite SLIT did not affect the results. CONCLUSION: Cedarcure® showed enhancement of the effects over the years of treatment by the analysis up to the third year. Both Cedar SLIT alone and Dual SLIT showed similar efficacy on cedar pollinosis.


Assuntos
Cryptomeria , Rinite Alérgica Sazonal , Imunoterapia Sublingual , Humanos , Rinite Alérgica Sazonal/terapia , Administração Sublingual , Resultado do Tratamento , Comprimidos , Alérgenos
15.
JAMA Netw Open ; 5(11): e2241743, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36374501

RESUMO

Importance: Half of women who are postmenopausal have genitourinary discomfort after menopause. Recommended therapies include low-dose vaginal estrogen. Individuals with a history of breast cancer or venous thromboembolism may have concerns about the safety of this intervention. Objective: To compare serum estrogen concentrations with the use of vaginal estrogen, 10 µg, tablet vs placebo in women who are postmenopausal. Design, Setting, and Participants: This is a secondary, post hoc analysis of data from a randomized clinical trial of treatment for moderate to severe genitourinary syndrome in women who are postmenopausal. The study was conducted at Kaiser Permanente Washington Health Research Institute and the University of Minnesota from April 11, 2016, to April 23, 2017. Measurements and data analysis were performed from November 3, 2020, to September 23, 2022. Interventions: Participants were randomly assigned to vaginal estradiol tablet (10 µg/d for 2 weeks and then twice weekly) plus placebo gel (3 times weekly) or dual placebo for 12 weeks. Main Outcomes and Measures: In this post hoc analysis, baseline and week 12 serum estradiol, estrone, and sex hormone-binding globulin (SHBG) concentrations were measured by a chemiluminescent assay. Week 12 values of the 3 analytes were compared by baseline participant characteristics. Linear models compared week 12 estradiol concentrations between treatment groups, adjusted for baseline characteristics. Results: A total of 174 women, mean (SD) age 61 (4) years, were included. Those in the estrogen group (n = 88) were more likely to have higher geometric mean (SD) week 12 serum estradiol concentrations (4.3 [2.2 pg/mL]) than those in the placebo group (n = 86) (3.5 [2.1] pg/mL) (P = .01). Adjusted for pretreatment hormone concentrations, age, clinical site, and body mass index, assignment to the estrogen vs placebo treatment group was significantly associated with higher week 12 estradiol concentrations (23.8% difference; 95% CI, 6.9%-43.3%). Most (121 of 174 [69.5%]) participants had enrollment serum estradiol concentrations higher than 2.7 pg/mL. Of women starting treatment at estradiol levels lower than or equal to 2.7 pg/mL, 38.1% (8 of 21) in the estrogen group and 34.4% (11 of 32) in the placebo group had estradiol concentrations higher than 2.7 pg/mL after 12 weeks of study participation (P = .78). Treatment assignment was not associated with week 12 estrone or SHBG concentrations. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, a significant, although small, increase in serum estradiol levels was noted after 12 weeks of vaginal estrogen administration. The clinical relevance of this small increase is uncertain. Trial Registration: ClinicalTrials.gov Identifier: NCT02516202.


Assuntos
Estradiol , Estrona , Humanos , Feminino , Pessoa de Meia-Idade , Pós-Menopausa , Cremes, Espumas e Géis Vaginais , Estrogênios , Comprimidos
16.
AAPS PharmSciTech ; 23(8): 301, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36385217

RESUMO

The absence of oral liquid pharmaceutical forms appropriate for use in pediatric and adult patients with difficulty swallowing is a public health problem, especially in the hospital context. Baclofen is a muscle relaxant of choice for treating spasticity, generally marketed only in tablet form, highlighting the need for liquid formulations to facilitate dose adjustment, administration, and swallowing. The present study aimed to develop oral liquid formulations containing baclofen, optimize them through the quality by design approach, and evaluate their physicochemical and microbiological stability. Preformulation and preliminary stability studies were carried out for the development of formulations. Experimental screening and optimization designs resulted in eleven experiments for each step that were evaluated for 28 days. A stability-indicating method by high-performance liquid chromatography presented linearity, low limits of detection and quantification, precision, accuracy, and robustness. The experimental design led to two optimized formulations containing baclofen, glycerin, potassium sorbate, citric acid, ultrapure water, flavor, and sucrose syrup or sodium carboxymethylcellulose solution as a vehicle, the last one with sucralose as a sweetener. The formulations were placed in amber glass flasks and subjected to a physicochemical and microbiological stability study. Both formulations showed physicochemical and microbiological stability when stored at room temperature and refrigerated for 84 days. The results of this study may serve as a reference in the preparation of liquid oral formulations containing baclofen in the hospital routine and collaborate with the safety and adherence to the treatment of adult and pediatric patients.


Assuntos
Baclofeno , Excipientes , Humanos , Criança , Estabilidade de Medicamentos , Composição de Medicamentos , Comprimidos , Excipientes/química , Hospitais
17.
J Prev Med Hyg ; 63(3): E456-E463, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36415291

RESUMO

Introduction: The low non-compliance to the consumption of Iron Tablets in pregnant women is an obstacle in the implementation of government programs to prevent and overcome the anemia problems in pregnant women. This study was conducted to determine the probability of non-compliance of pregnant women in the consumption of iron tablets in Indonesia. Methods: A cross-sectional study using the 2017 IDHS data. The sample was 12,466 women of childbearing age 15-49 years in Indonesia who consumed Iron Tablets during their last pregnancy. Univariate analysis used proportion measure, the bivariate analysis using chi-square test and multivariate used binary logistic regression test. Statistical analysis using SPSS-26 software. Results: The level of non-compliance to the consumption of Iron Tablets during pregnancy in Indonesia is only 48.47%. The risk factors for quantity (p = 0.000, OR 2.085), and quality (p = 0.000, OR 1.655) Antenatal Care (ANC) was not good, examiners were pregnancy not health workers (p = 0.000, OR 1.816), residence in rural areas (p = 0.000, OR 1.262), and very poor socioeconomic status (p value = 0.000, OR 2.041) were significantly related to non-compliance with Iron Tablets consumption. The probability of non-compliance to the consumption of Iron Tablets in pregnant women with risk factors is 88%. Conclusion: Quantity of ANC and socioeconomic have a high influence on compliance to consumption of iron tablets, so it is important to bring nutrition workers at ANC activities to educate pregnant women about the benefits, side effects, and ways of consumption of iron tablets, reactivate supervisors for consumption of iron tablets, increase access health services in rural areas and families with low socioeconomic status, as well as providing free health care programs for the poor.


Assuntos
Ferro , Gestantes , Gravidez , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Ferro/uso terapêutico , Indonésia , Estudos Transversais , Comprimidos , Fatores de Risco
18.
AAPS PharmSciTech ; 23(8): 290, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316610

RESUMO

This study explores the dissolution mechanism and absorption process of compound Danshen tablets (CDTs) and compound Danshen capsules (CDCs) in vitro. Taking the cell index as the evaluation index of dissolution and absorption of multi-component solid preparations of CDTs and CDCs, it breaks through the idea of traditional research. We used real-time cell-based assay (RTCA) to provide a new idea and method for the consistency evaluation of traditional Chinese medicine (TCM) compound preparations. The drug dissolution and absorption simulation system (DDASS) was established to obtain the dissolution and absorption samples of compound Danshen solid preparations at different time points. The cell index (CI) of the sample to H9C2 cells was detected by RTCA technology, and the dissolution and absorption percentage were calculated based on this index to obtain the dissolution and absorption kinetics model. Meanwhile, one batch of tablets and one batch of capsules (batch numbers ZKC1816 and 202101001) were selected to conduct the overall animal pharmacodynamic experiment to verify the feasibility of drug effect evaluation with cell index as an indicator. The best fitting model of dissolution curves of each batch of CDTs and CDCs is the Weibull model. There was a good correlation (r > 0.86) between the dissolution-absorption-pharmacodynamic curve. Based on RTCA technology, we have established the comprehensive evaluation method for cell biology of compound Danshen solid preparations in line with the overall concept of TCM and a synchronous evaluation system of dissolution and absorption in vitro of new TCM compound solid preparations.


Assuntos
Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Animais , Cápsulas , Solubilidade , Comprimidos , Medicina Tradicional Chinesa
19.
Low Urin Tract Symptoms ; 14(6): 410-415, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36319193

RESUMO

OBJECTIVES: To clarify Japanese real-world clinical data on the use of desmopressin 25 and 50 µg orally disintegrating tablets (ODT) for male patients with nocturia and evaluate the predictive factors to improve nighttime frequency. METHODS: We retrospectively accumulated real-world clinical data from 27 institutions in Japan. Male patients with two or more episodes of nocturia who received desmopressin ODT for nocturnal polyuria (NP) from 2019 through 2021 were included. The primary endpoint was the change of nighttime frequency until 3 months after desmopressin administration. The secondary endpoints were to clarify the persistence rate, adverse events, and predictive factors of decreasing nighttime frequency. RESULTS: A total of 118 patients were eligible to participate in this study. The persistence rate of desmopressin on the Kaplan-Meier curve at week 12 was 51.3. The reason for discontinuation was mainly the occurrence of adverse events in 67 patients (56.8%), particularly hyponatremia in 7 patients (5.9%). Nighttime frequencies at baseline, - 1 month and 1 - 3 months after desmopressin administration were 4.1 ± 1.3, 2.9 ± 1.4 (P < .01), and 2.6 ± 1.3 (P < .01), respectively. The mean nighttime urine volume voided at baseline was significantly larger in patients whose nighttime frequency decreased by two or more times than in those with a decrease of less than two times. CONCLUSIONS: Desmopressin 25 and 50 µg ODT treatments are feasible for male patients with NP in Japanese real-world clinical practice. Patients with higher voided volumes, particularly in the nighttime, may have great benefit from desmopressin.


Assuntos
Noctúria , Humanos , Masculino , Desamino Arginina Vasopressina , Japão , Estudos Retrospectivos , Comprimidos
20.
Molecules ; 27(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364096

RESUMO

Anthocyanins obtained from jambolan have been used as active agents in different carboxymethyl starch-based tablet formulations and their release profiles evaluated in simulated gastric fluids (SGF) and simulated intestinal (SIF) fluids. Structural analysis highlighted a strong interaction between anthocyanins and carboxymethyl starch, evidenced by scanning electron microscopy and infrared analysis. Tablet dissolution behavior varied according to the pH of the media, being controlled by the swelling and/or erosion of the polymeric matrix. Various formulations for immediate, fast, and sustained release of anthocyanins for 30 min, 2 h and 12 h of dissolution have been developed. It was found that monolithic carboxymethyl starch tablets loaded with powdered jambolan extract efficiently afforded the complete delivery (100% of anthocyanins) to different sites of the simulated gastrointestinal tract and ensured the stability of these pigments, which maintained their antioxidant activity.


Assuntos
Antocianinas , Excipientes , Excipientes/química , Preparações de Ação Retardada , Amido/química , Comprimidos/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...