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1.
Chem Pharm Bull (Tokyo) ; 71(2): 165-174, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36724979

RESUMO

In the present study, we conducted a detailed evaluation of the effects of humidification on the quality of five types of commercial magnesium oxide (MgO) tablet formulations. When near-IR spectroscopy was performed, a peak derived from the first overtone of the stretching vibration of the hydroxyl group was observed at approximately 7200 cm-1 in a humidified MgO tablet formulation. To visually evaluate the effect of this humidification, a mapping image was created using microscopic IR spectroscopy. In the IR spectrum, a peak derived from the stretching vibration of the hydroxyl group appears at approximately 3700 cm-1, so we created a mapping image using the absorbance ratio of 3700 and 3400 cm-1 as an index. In the mapping image of humidified MgO tablet formulations, many areas had a higher absorbance ratio than the dried tablet formulations. From these results, it is qualitatively confirmed that the MgO was changed to magnesium hydroxide (Mg(OH)2) by humidification. Although these results were observed in the four types of MgO tablet formulations, only one type of tablet formulation was less affected by humidification. In addition, although most tablet formulations tended to prolong disintegration time due to humidification, there was almost no effect of humidification on the disintegration time in one type of tablet formulation, which had little change in the above evaluation. Thus, in most commercial MgO tablet formulations, humidification prolongs the disintegration time, and Mg(OH)2 significantly contributes to this factor.


Assuntos
Óxido de Magnésio , Óxido de Magnésio/química , Dureza , Comprimidos/química , Solubilidade
2.
Zhongguo Zhong Yao Za Zhi ; 48(1): 247-255, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36725277

RESUMO

This study aims to evaluate the efficacy and safety of Guanxinning Tablets+conventional western medicine in the treatment of angina pectoris of coronary heart disease, and provide evidence-based references for clinical medication. Retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, randomized controlled trial(RCT) about Guanxinning Tablets for the treatment of angina pectoris of coronary heart disease from the inception to April 2022 were collected. After literature screening and data extraction, the bias risk assessment tool recommended by the Cochrane evaluation manual handbook 5.1.0 was used to evaluate the quality of the included literature, and RevMan 5.3 and Stata 14.0 were used for Meta-analysis. Eighteen RCTs were finally included, involving 2 281 patients. Meta-analysis showed that, compared with conventional western medicine treatment alone, Guanxinning Tablets+conventional western medicine significantly improved angina pectoris efficacy(RR=1.33, 95%CI[1.13, 1.57], P=0.000 8), electrocardiogram efficacy(RR=1.32, 95%CI[1.02, 1.71], P=0.03), and exercise duration(MD=59.53, 95%CI[39.16, 79.90], P<0.000 01) and reduced the incidence of cardiovascular events(MACE)(RR=0.43, 95%CI[0.30, 0.61], P<0.000 01), high sensitivity C-reactive protein(hs-CRP)(MD=-2.75, 95%CI[-3.71,-1.79], P<0.000 01), and endothelin-1(ET-1) levels(MD=-9.34, 95%CI[-11.36,-7.32], P<0.000 01). There was no statistically significant difference in the incidence of adverse reactions between two groups(RR=0.91, 95%CI[0.68, 1.22], P=0.52). Subgroup analysis showed that Guanxinning Tablets may have better short-term efficacy(less than 6 months) in the treatment of heart-blood stasis syndrome. GRADE grading showed that angina pectoris efficacy, electrocardiogram efficacy, MACE, and ET-1 were in the medium grade, hs-CRP and adverse reactions were in the low grade, and exercise duration was in the extremely low grade. In conclusion, the efficacy of Guanxinning Tablets+conventional western medicine is better than conventional western medicine treatment alone, with good safety. Therefore, it is recommended for the short-term treatment of patients with heart-blood stasis syndrome. However, the evidence quality of some results is low, and more rigo-rous RCT is still needed to enhance the reliability of evidence.


Assuntos
Doença das Coronárias , Medicamentos de Ervas Chinesas , Humanos , Proteína C-Reativa , Reprodutibilidade dos Testes , Medicamentos de Ervas Chinesas/efeitos adversos , Angina Pectoris/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Comprimidos
3.
Drug Des Devel Ther ; 17: 261-272, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36726738

RESUMO

Background: Self-emulsifying drug-delivery systems (SEDDSs) are designed to improve the oral bioavailability of poorly water-soluble drugs. This study aimed at formulating and characterization of SEDDS-based tablets for simvastatin using castor and olive oils as solvents and Tween 60 as surfactant. Methods: The liquids were adsorbed on microcrystalline cellulose, and all developed formulations were compressed using 10.5 mm shallow concave round punches. Results: The resulting tablets were evaluated for different quality-control parameters at pre- and postcompression levels. Simvastatin showed better solubility in a mixture of oils and Tween 60 (10:1). All the developed formulations showed lower self-emulsification time (˂200 seconds) and higher cloud point (˃60°C). They were free of physical defects and had drug content within the acceptable range (98.5%-101%). The crushing strength of all formulations was in the range of 58-96 N, and the results of the friability test were within the range of USP (≤1). Disintegration time was within the official limits (NMT 15 min), and complete drug release was achieved within 30 min. Conclusion: Using commonly available excipients and machinery, SEDDS-based tablets with better dissolution profile and bioavailability can be prepared by direct compression. These S-SEDDSs could be a better alternative to conventional tablets of simvastatin.


Assuntos
Polissorbatos , Sinvastatina , Polissorbatos/química , Sinvastatina/química , Emulsões/química , Sistemas de Liberação de Medicamentos/métodos , Solubilidade , Disponibilidade Biológica , Comprimidos/química , Administração Oral
4.
AAPS PharmSciTech ; 24(1): 52, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703088

RESUMO

Semha-Pinas (SHPN) is a Thai traditional herbal formula used as an expectorant. Its traditional dosage form is pills, which are dispersed in water before use. The development of this recipe to effervescent tablets could enhance patient convenience with shortened the time needed to disintegrate the active ingredients. This work aimed to develop SHPN extract effervescent tablets based on process and formulation optimization using the Box-Behnken design. Four levels of three independent variables, including a compressional force, a quantity of effervescent base, and a quantity of fumed silica, were screened using the one factor at a time method. Three levels of each independent variable were included in the Box-Behnken design, including 1000 - 2000 psi, 46 - 52%, and 1.67 - 3.33%, respectively. Four responses were monitored, including tablet thickness, hardness, disintegration time, and friability. In terms of design space, the results showed that the tablet hardness was not less than 5 kP, disintegration time was not more than 5 min, and friability was not more than 1% found when 2000 psi compressional force was used. The optimal parameters were a compressional force of 2000 psi, effervescent base of 50%, and fumed silica of 2.5%. This formulation had a tablet weight of 598.86 ± 0.05 mg, a diameter of 12.68 ± 0.01 mm, a thickness of 3.67 ± 0.01 mm, a hardness of 5.57 ± 0.22 kP, a disintegration time of 1.68 ± 0.04 min, and friability of 0.43 ± 0.02%. In conclusion, this work succeeded in developing SHPN extract effervescent tablets with desired properties that were easy to use. Furthermore, the time needed to disintegrate the active ingredients was decreased when compared with the traditional dosage form due to being easily dissolved in water.


Assuntos
Dióxido de Silício , Água , Humanos , Comprimidos , Solubilidade
5.
Drugs ; 83(1): 75-86, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36607589

RESUMO

BACKGROUND: Posaconazole is widely used for the prophylaxis and treatment of invasive fungal diseases. Because of the limited and variable absorption of the initially available oral suspension, a delayed-release tablet and intravenous formulation were developed. OBJECTIVE: This study aimed to characterize the pharmacokinetics, including the absolute oral bioavailability, of all posaconazole formulations in healthy volunteers. METHODS: Data from 182 healthy volunteers with 3898 densely sampled posaconazole concentrations were pooled from eight phase I clinical studies on the three formulations of various single and multiple dosage regimens between 50 and 400 mg. Analysis and simulations were performed using NONMEM 7.5.0. In the covariate analysis, the influence of food (fed vs fasted), nonlinearity, and for the delayed-release tablet, comedication (antacid, ranitidine, esomeprazole, and metoclopramide) were tested. RESULTS: A two-compartment model with respectively, four and eight absorption transit compartments, best described the profiles of the oral suspension and delayed-release tablet. For the suspension, both a food effect and a dose-dependent nonlinear bioavailability were quantified, resulting in lower bioavailability when fasted or at a higher dose. The typical bioavailability of the suspension at 100 mg and 400 mg was derived to be respectively, 17.1% and 10.1% under fasted conditions and 59.1% and 49.2% under fed conditions. The absolute bioavailability of the delayed-release tablet was 58.8% (95% confidence interval 33.2-80.4) under fasted conditions and approached complete absorption under fed conditions for dosages up to 300 mg. Food intake reduced the absorption rate constant of the suspension by 52.2% (confidence interval 45.2-59.2). The impact of comedication on the absorption of the delayed-release tablet was not statistically significant. Model-based simulations indicate that under fed conditions, the licensed dosages of the three formulations yield a steady-state trough concentration ≥ 0.7 mg/L in over 90% of healthy volunteers. About 35% of healthy volunteers who receive the licensed 300-mg delayed-release tablet under fasted conditions do not achieve this target, while for the suspension this percentage varies between 55 and 85%, depending on the dose. CONCLUSIONS: For both oral posaconazole formulations, we quantified bioavailability and absorption rate, including food effects, in healthy volunteers. The pharmacokinetic superiority of the delayed-release tablet was demonstrated under both fed and fasted conditions, compared with the oral suspension. The impact of food on the bioavailability of the delayed-release tablet was larger than anticipated, suggesting that administering the delayed-release tablet with food enhances absorption.


Assuntos
Antifúngicos , Triazóis , Humanos , Infusões Intravenosas , Voluntários Saudáveis , Disponibilidade Biológica , Suspensões , Comprimidos , Administração Oral , Estudos Cross-Over
6.
PLoS One ; 18(1): e0280212, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36608031

RESUMO

BACKGROUND & AIMS: Fentanyl buccal tablets (FBTs) are a rapid-onset opioid indicated for breakthrough cancer pain (BTcP) and FBT titration is needed to optimize BTcP management. We aimed to predict which patients could tolerate a high dose of FBT (400 µg or more at a time). METHODS: A retrospective analysis was performed to assess the final FBT dose. The final FBT doses were compared according to the clinical features. The prediction accuracy of patients tolerant of 400 µg or higher FBT was compared using the area under the receiver operating characteristic (ROC) curves. A risk scoring model based on the odds ratio (OR) was developed from the final multivariable model, and patients were assigned into two groups: low tolerance (0-1 point) and high tolerance (2-3 points). RESULTS: Among 131 patients, the most frequently effective dose of FBT was 200 µg (54%), followed by 100 µg (30%). The median value of morphine equivalent daily doses (MEDD) was 60 mg/day, and the most common daily use was 3-4 times/day. In multivariable analysis, male sex, younger age, and use of FBTs three or more times per day were independently associated with high-dose FBT. According to the risk scoring model, the patients with a final FBT of 400 µg or higher were significantly more in the high tolerance group (17%) compared to the low tolerance group (3%; p = 0.023). CONCLUSIONS: According to the dose relationship between the final FBT dose and the clinical features, three factors (sex, age, daily use of FBT) were independently associated with the final dose of FBT. Our risk score model could help predict tolerance to high-dose FBT and guide the titration plan for BTcP.


Assuntos
Dor Irruptiva , Neoplasias , Humanos , Masculino , Analgésicos Opioides/efeitos adversos , Estudos Retrospectivos , Administração Bucal , Medição da Dor , Comprimidos/uso terapêutico , Fentanila/efeitos adversos , Dor Irruptiva/complicações , Dor Irruptiva/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Resultado do Tratamento
7.
Eur J Pharm Sci ; 182: 106374, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36623699

RESUMO

Therapeutic proteins and peptides (TPPs) are increasingly favoured above small drug molecules due to their high specificity to the site of action and reduced adverse effects resulting in increased use of these agents for medical treatments and therapies. Consequently, there is a need to formulate TPPs in dosage forms that are accessible and suitable for a wide range of patient groups as the use of TPPs becomes increasingly prevalent in healthcare settings worldwide. Orally disintegrating dosage forms (ODDF) are formulations that can ensure easy-to-administer medication to a wider patient population including paediatrics, geriatrics and people in low-resource countries. There are many challenges involved in developing suitable pharmaceutical strategies to protect TPPs during formulation and manufacturing, as well as storage, and maintenance of a cold-chain during transportation. This review will discuss advances being made in the research and development of pharmaceutical and manufacturing strategies used to incorporate various TPPs into ODDF systems.


Assuntos
Sistemas de Liberação de Medicamentos , Peptídeos , Criança , Humanos , Administração Oral , Formas de Dosagem , Sistemas de Liberação de Medicamentos/métodos , Preparações Farmacêuticas/química , Comprimidos/química , Idoso
8.
Molecules ; 28(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36615620

RESUMO

A key step in the development of medicinal products is the research and validation of selective and sensitive analytical methods for the control of impurities from synthesis and degradation. As most impurities are similar in structure to the drug substance, the achievement of chemo-selective conditions is usually challenging. Herein, a direct and highly selective ultra-high-performance liquid chromatographic method for determining the assay and related substances content in medicinal products containing rosuvastatin calcium salt (RSV) is presented. RSV is used to treat high cholesterol levels and prevent heart attacks and strokes. The most engaging feature of this method was the baseline separation of all organic related substances listed in the European Pharmacopoeia (EP) monograph for the RSV tablets, achieved for the first time in less than 15 min using the Acquity BEH C18 (100 mm × 2.1 mm, 1.7 µm) column under reversed-phase isocratic conditions. The mobile phase adopted for the chemo-selective analysis does not contain buffers but instead contains trifluoroacetic as an acid additive. The chromatographic method was validated according to the guidelines of the International Conference on Harmonization (ICH) and proved to be linear, precise and accurate for determining the content of RSV and related chiral substances in tablet formulations.


Assuntos
Rosuvastatina Cálcica , Limite de Detecção , Cromatografia Líquida de Alta Pressão/métodos , Comprimidos , Reprodutibilidade dos Testes
9.
AAPS PharmSciTech ; 24(1): 32, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627414

RESUMO

Migraine headaches are usually intolerable, and a quick-relief treatment remains an unmet medical need. Almotriptan malate is a serotonin (5-HT1B/1D) receptor agonist approved for the treatment of acute migraine in adults. It is currently available in an oral tablet dosage form and has a Tmax of 1-3 h, and therefore, there is a medical need to develop a non-invasive rapidly acting formulation. We have developed an intranasal formulation of almotriptan malate using the quality-by-design (QbD) approach. A 2-factor 3-level full factorial design was selected to build up the experimental setting. The developed formulation was characterized for pH, viscosity, in vitro permeation, ex vivo permeation, and histopathological tolerance. To assess the potential of the developed formulation to produce a rapid onset of action following intranasal delivery, a pharmacokinetic study was performed in the Sprague-Dawley rat model and compared to the currently available marketed oral tablet formulation. For this, the LC-MS/MS bioanalytical method was developed and used for the determination of plasma almotriptan malate concentrations. Results of a pharmacokinetic study revealed that intranasal administration of optimized almotriptan malate formulation enabled an almost five-fold reduction in Tmax and about seven-fold increase in bioavailability in comparison to the currently available oral tablet formulation, suggesting the potential of developed almotriptan malate intranasal formulation in producing a rapid onset of action as well as enhanced bioavailability.


Assuntos
Transtornos de Enxaqueca , Agonistas do Receptor de Serotonina , Animais , Ratos , Administração Intranasal , Cromatografia Líquida , Agonistas do Receptor de Serotonina/farmacocinética , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Triptaminas/farmacocinética , Transtornos de Enxaqueca/tratamento farmacológico , Serotonina/uso terapêutico , Comprimidos
10.
Forensic Toxicol ; 41(1): 59-70, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36652055

RESUMO

PURPOSE: The information on analytical methods for 4-quinazolinone recreational drugs, such as methaqualone, etaqualone and 2-methoxyqualone, is almost scant. In this study, product ion spectra of gas chromatography-tandem mass spectrometry (GC-MS/MS) with different collision energies were presented for these drugs. Because 2-methoxyqualone is a new recreational drug discovered in dubious tablets very recently, much more detailed data obtained by different types of mass spectrometry instruments, and quantification data of 2-methoxyqualone in the tablet together with its validation were demonstrated. METHODS: The methods for analyses were GC-MS/MS, high-resolution ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and liquid chromatography-tandem mass spectrometry. RESULTS: The GC-MS/MS product ion spectra of the three compounds with different collision energies have not been reported before. They were very useful to tentatively identify unknown compounds. If a reference standard is available, the final identification and quantification can be achieved by measurements of product ion spectra and in selected reaction monitoring mode very easily by GC-MS/MS. The final identification and quantification for the new 2-methoxyqualone were performed in this way. The content of the compound was 69.8 ± 0.5% (w/w) in the tablet. Acetaminophen and caffeine coexisted in the tablet with approximate concentrations at 10 and 5%, respectively. CONCLUSIONS: In this article, we have presented product ion spectra of methaqualone, etaqualone and 2-methoxyqualone at different collision energies by GC-MS/MS for the first time. In addition, this is the first paper to describe the details of quantification of 2-methoxyqualone in the authentic seized product.


Assuntos
Metaqualona , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Comprimidos
11.
Clin Ter ; 174(1): 23-27, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36655640

RESUMO

Introduction: This study aimed to evaluate the antibiofilm effect of different agents (neutral soap, 4% chlorhexidine, Efferdent effervescent tablets, 1% triclosan, and citronella essential oil) used for ocular prosthesis cleaning. Material and Methods: Biofilms of S. aureus and S. epidermidis were formed on 60 ocular prosthesis acrylic resin specimens. The specimens were cleaned with the studied agents with different techniques. Microorganism counting was performed. Data were submitted to ANOVA and HSD Tukey-Kramer (p<.01). Results: When compared to the control group, all cleaning protocols promoted a reduction in growth of microorganisms. The 4% chlorhexidine, effervescent tablets, and 1% triclosan cleaning agents eliminated biofilm in all groups. Conclusion: Therefore, immersion in 4% chlorhexidine, effervescent tablets, and 1% triclosan could be the best protocols indicated for ocular prosthesis cleaning due to their ability to eliminate biofilm.


Assuntos
Clorexidina , Triclosan , Humanos , Clorexidina/farmacologia , Olho Artificial , Staphylococcus aureus , Triclosan/farmacologia , Biofilmes , Comprimidos/farmacologia
12.
BMC Prim Care ; 24(1): 25, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681795

RESUMO

BACKGROUND: Primary healthcare (PHC) services are crucial in supporting people who use substances. The aims of this study were to explore the experiences of Aboriginal males in NSW in treatment for substance use about speaking about their substance use with PHC staff, and their preferences for accessing PHC about their substance use. METHODS: Semi-structured interviews with residential drug and alcohol rehabilitation treatment service clients. Thematic analysis was used to develop themes inductively and deductively. Two interviews were independently double coded by an Aboriginal researcher and the project was supported by an Aboriginal Advisory Group. RESULTS: Twenty male adults who self-identified as Aboriginal participated (mean age 27 years). Half reported visiting PHC and talking about their substance use before their residential service stay. Two major themes developed: (1) speaking up about substance use or mental health problems linked with substance use, (2) ways to improve access to PHC about substance use. Although some males were offered treatment, some were not, and others had concerns about the treatments offered. CONCLUSION: This research highlights opportunities to improve access and to better support Aboriginal males who use substances in PHC. Focus on culturally appropriate PHC and providing staff with training around substance use and treatment options may improve access. It is important to foster culturally appropriate services, develop PHC staff knowledge around substance use, focus on therapeutic relationships and have a range of treatment options available that can be tailored to individual circumstances.


Assuntos
Comportamento Aditivo , Transtornos Relacionados ao Uso de Substâncias , Adulto , Humanos , Masculino , Havaiano Nativo ou Outro Ilhéu do Pacífico/psicologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Atenção Primária à Saúde , Comprimidos
13.
BMC Cancer ; 23(1): 66, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658529

RESUMO

BACKGROUND: Historically, high hepatocellular carcinoma (HCC)-related mortality has been, in part, due to lack of effective therapies; however, several systemic therapies have been recently approved for HCC treatment, including regorafenib and ramucirumab. These two treatments utilize different routes of administration (four daily tablets and biweekly intravenous infusions, respectively) and have different risks of adverse events (AEs). However, we lack data on patient preferences in balancing the route of administration and risk of AEs in patients with HCC. We aimed to determine patient preferences and trade-offs for second-line treatment in patients with HCC.  METHODS: Patients with advanced or metastatic HCC were recruited through their physicians for this study. Patient preferences were assessed by using a modified threshold technique (TT) design in which respondents were asked two direct-elicitation questions before (assuming same safety and efficacy and only varying mode of administration) and after (incorporating the safety profiles of ramucirumab and regorafenib) the TT series on seven risks of clinically relevant AEs. RESULTS: In total, of the 157 patients recruited by their physicians, 150 were eligible and consented to participate. In the first elicitation question (assuming risk and efficacy were equivalent), 61.3% of patients preferred daily tablets. However, 76.7% of patients preferred the biweekly infusion when the safety profiles of the two available second-line therapies were included. The TT analysis confirmed that preferences for oral administration were not strong enough to balance out the risk of AEs that differentiate the two therapies. DISCUSSION: We found that when patients were asked to choose between a daily, oral medication and a biweekly IV medication for HCC, they were more likely to choose a daily, oral medication if efficacy and safety profiles were the same. However, when risks of AEs representing the safety profiles of two currently available second-line treatments were introduced in a second direct-elicitation question, respondents often selected an IV administration with a safety profile similar to ramucirumab, rather than oral tablets with a safety profile similar to regorafenib. Our findings indicate that the risk profile of a second-line treatment for HCC may be more important than the mode of administration to patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Preferência do Paciente , Comprimidos/uso terapêutico
14.
Acta Pharm ; 73(1): 107-119, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36692467

RESUMO

This study aimed to elucidate the characteristics and pharmacokinetics of orally disintegrating tablets (ODTs) containing coenzyme Q10 (CoQ10) granules prepared by spray drying, hot-melting, and wet granulation. The hardness and disintegration times of CoQ10-ODTs containing 5 % crospovidone were 61.6-81.8 N and < 30 s, respectively; these values indicate that the as-prepared ODTs were adequate for clinical use. The hardness and disintegration times of all ODTs did not change significantly after a 28-day storage period at 30 °C/10 % relative humidity (RH), but storage under high temperature and humidity affected their characteristics. The dissolution and pharmacokinetics of CoQ10-ODTs showed that ODTs prepared using the spray-drying method had the highest dissolution and absorbability among the CoQ10-ODTs tested. These results provide useful information for the preparation of ODTs using CoQ10.


Assuntos
Solubilidade , Composição de Medicamentos/métodos , Dureza , Comprimidos , Administração Oral
15.
Pharm Biol ; 61(1): 271-280, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36655371

RESUMO

CONTEXT: Therapeutic effects of Qiangjing tablets (QJT) on sperm vitality and asthenozoospermia (AZS) have been confirmed. However, the mechanism of action remains unclear. OBJECTIVE: This study investigates the effects of QJT on AZS and the underlying mechanism of action. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were randomly divided into six groups: Control, ORN (ornidazole; 200 mg/kg), ORN + QJT-low (0.17 g/mL), ORN + QJT-middle (0.33 g/mL), ORN + QJT-high (0.67 g/mL), and ORN + QJT + Radicicol (0.67 g/mL QJT and 20 mg/kg radicicol) groups. Pathological evaluation and analysis of mitophagy were conducted by H&E staining and transmission electron microscopy, respectively. Reactive oxygen species were detected by flow cytometry. Protein expression was determined by Western blotting. RESULTS: QJT significantly improved ORN-treated sperm motility and kinematic parameters, as well as the pathological symptoms of testicular and epididymal tissues. In particular, QJT mitigated impaired mitochondrial morphology, and increased the PHB, Beclin-1, LC3-II protein, and ROS levels (p < 0.05), and reduced the protein expression levels of LC3-I and p62 (p < 0.05). Mechanistically, QJT antagonized the downregulation of SCF and Parkin protein levels (p < 0.05). Furthermore, QJT significantly increased the protein expressions levels of LKB1, AMPKα, p-AMPKα, ULK1 and p-ULK1 (p < 0.05). The ameliorative effect of QJT on pathological manifestations, mitochondrial morphology, and the expressions of mitophagy and mitochondrial ubiquitination-related proteins was counteracted by radicicol. DISCUSSION AND CONCLUSIONS: QJT improved AZS via mitochondrial ubiquitination and mitophagy mediated by the LKB1/AMPK/ULK1 signaling pathway. Our study provides a theoretical basis for the treatment of AZS and male infertility.


Assuntos
Astenozoospermia , Medicamentos de Ervas Chinesas , Animais , Masculino , Ratos , Proteínas Quinases Ativadas por AMP , Astenozoospermia/tratamento farmacológico , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Medicamentos de Ervas Chinesas/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/uso terapêutico , Mitofagia , Ratos Sprague-Dawley , Sêmen , Motilidade Espermática , Comprimidos/uso terapêutico , Ubiquitinação
16.
Sci Rep ; 13(1): 1113, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670124

RESUMO

Omeprazole and sodium bicarbonate dry suspension are effective treatments for acid-related disorders. This study compared the bioequivalence and safety of the two formulations of omeprazole and sodium bicarbonate powder and assessed how CYP2C19 gene polymorphisms affect pharmacokinetics (PK). A single-center, randomized, single-dose, 2-sequence and 2-period crossover method was performed in forty healthy Chinese subjects. Blood samples were collected after a single dose for PK (AUC0-∞, AUC0-t, and Cmax) analysis. The concentrations of Omeprazole in human plasma were determined by HPLC-MS/MS. Besides, the gene polymorphisms of CYP2C19 were assessed by Sanger sequencing. The geometric mean ratios (90% confidence interval) [GMR (95% CI)] of Test/Reference preparation for Cmax: 95.2% (88.48%, 102.43%), AUC0-t: 97.47% (94.4%, 101.02%), AUC0-∞: 97.68% (94.27%, 101.21%) were within the range of 80.00-125.00%. The non-parametric test showed no statistical difference in Tmax between the two groups (p > 0.05). All drugs were well tolerated, no severe adverse reactions occurred, and no significant differences in adverse events between the two drugs. For CYP2C19 gene polymorphisms, the results showed that of 40 subjects, 12 subjects were extensive metabolizers, 24 were intermediate metabolizers, and 4 were poor metabolizers, the frequency of metabolic genotypes were 30%, 60%, and 10%. And the allele distributions for CYP2C19 were *1, *2, and *3 at 60%, 38.75%, and 1.25%. Both the CYP2C19 alleles and metabolic genotypes were consistent with other studies in Chinese. The results of PK parameters showed that different genotypes of CYP2C19 lead to significant differences in t1/2, AUC0-t, AUC0-∞ and Cmax, but no significant differences in Tmax in each group. At the same time, we confirmed that the PK parameters of the test and reference had no differences between the males and females. This study has shown that the pharmacokinetic parameters of the two formulations are not significantly different, which showed bioequivalence and exemplary safety. CYP2C19 gene polymorphism significantly differed in the PK parameters of omeprazole sodium bicarbonate powder.


Assuntos
Espectrometria de Massas em Tandem , Masculino , Feminino , Humanos , Equivalência Terapêutica , Citocromo P-450 CYP2C19/genética , Pós , Bicarbonato de Sódio , Omeprazol , Área Sob a Curva , Voluntários , Estudos Cross-Over , Voluntários Saudáveis , Comprimidos
17.
Int J Pharm Compd ; 27(1): 60-71, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36720063

RESUMO

The objective of this study was to prepare and evaluate ibuprofen nanocrystals using isopropyl alcohol and stabilizer sodium lauryl sulphate by way of the precipitation method. The nanocrystals were prepared by the bottom-up approach of the precipitation technique. This technique involves the use of an organic phase, which is completely miscible in the external aqueous phase. The ratio used for organic solvent-to-aqueous solvent was 1:50. The Fourier Transform Infrared Spectroscopy analyses confirmed that the drug and excipients were compatible, and the differential scanning calorimetry results indicated that the precipitation method led to no change in the crystalline structure of the drug. Scanning electron microscopy analysis of ibuprofen nanocrystals showed the promising size reduction of pure drug ibuprofen. Differential light scattering technique showed significant decrease in particle size and good stability of ibuprofen nanocrystals. Ibuprofen nanocrystals increased 20% to 25% of the saturation solubility of ibuprofen nanocrystals. Ibuprofen nanocrystals showed 90% drug release in the dissolution medium within 1 hour, while the pure drug and market product were dissolved only up to 58% and 63%, respectively. Ibuprofen nanocrystals increased the saturation solubility and in vitro dissolution of the drug as compared to conventional market product.


Assuntos
Ibuprofeno , Nanopartículas , Ibuprofeno/química , Excipientes/química , Solventes , Água , Solubilidade , Nanopartículas/química , Comprimidos/química
18.
J Med Internet Res ; 25: e42563, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36630650

RESUMO

BACKGROUND: During the COVID-19 pandemic, as health care services shifted to video- and phone-based modalities for patient and provider safety, the Veterans Affairs (VA) Office of Connected Care widely expanded its video-enabled tablet program to bridge digital divides for veterans with limited video care access. OBJECTIVE: This study aimed to characterize veterans who received and used US Department of VA-issued video-enabled tablets before versus during the COVID-19 pandemic. METHODS: We compared sociodemographic and clinical characteristics of veterans who received VA-issued tablets during 6-month prepandemic and pandemic periods (ie, from March 11, 2019, to September 10, 2019, and from March 11, 2020, to September 10, 2020). Then, we examined characteristics associated with video visit use for primary and mental health care within 6 months after tablet shipment, stratifying models by timing of tablet receipt. RESULTS: There was a nearly 6-fold increase in the number of veterans who received tablets in the pandemic versus prepandemic study periods (n=36,107 vs n=6784, respectively). Compared to the prepandemic period, tablet recipients during the pandemic were more likely to be older (mean age 64 vs 59 years), urban-dwelling (24,504/36,107, 67.9% vs 3766/6784, 55.5%), and have a history of housing instability (8633/36,107, 23.9% vs 1022/6784, 15.1%). Pandemic recipients were more likely to use video care (21,090/36,107, 58.4% vs 2995/6784, 44.2%) and did so more frequently (5.6 vs 2.3 average encounters) within 6 months of tablet receipt. In adjusted models, pandemic and prepandemic video care users were significantly more likely to be younger, stably housed, and have a mental health condition than nonusers. CONCLUSIONS: Although the COVID-19 pandemic led to increased distribution of VA-issued tablets to veterans with complex clinical and social needs, tablet recipients who were older or unstably housed remained less likely to have a video visit. The VA's tablet distribution program expanded access to video-enabled devices, but interventions are needed to bridge disparities in video visit use among device recipients.


Assuntos
COVID-19 , Telemedicina , Veteranos , Estados Unidos/epidemiologia , Humanos , Pessoa de Meia-Idade , Veteranos/psicologia , Estudos de Coortes , COVID-19/epidemiologia , Pandemias , United States Department of Veterans Affairs , Comprimidos
19.
Eur J Pharm Sci ; 182: 106373, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36623698

RESUMO

OBJECTIVE: The aim of this study was to examine the pharmacokinetics, bioequivalence, and safety of two tablet formulations of capecitabine 500 mg in Chinese patients with breast, colorectal or gastric cancer under fed condition. METHODS: A multicentric, randomized, open-label, single-dose, two-period, two-way crossover trial was conducted by randomizing a single oral dose of test (T) or reference (R, Xeloda®) capecitabine (500 mg) to patients of either sex with colon, colorectal or breast cancer under fed condition (high-fat and high-calorie diet). Pharmacokinetic parameters were calculated using non-compartmental methods. Patients were monitored for safety and tolerability throughout the study. RESULTS: 74 subjects were randomly enrolled. The T/R geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for Cmax, AUC0-t and AUC0-∞ of capecitabine were 96.60% (85.87-108.67%), 99.07% (95.40-102.89%), 99.17% (95.29-103.21%), respectively. All 90% CIs fell within the bioequivalence acceptance range of 80.00-125.00%. The common adverse events (AEs) included clinically significant laboratory abnormalities and gastrointestinal diseases. There were no serious adverse events (SAEs) or deaths during the study. No subject withdrew from the study due to AEs. CONCLUSION: Single oral intake of test and the reference capecitabine tablets were bioequivalent under fed condition and had similar favourable safety profiles in Chinese patients with breast, colorectal or gastric cancer. TRIAL REGISTRATION: chinadrugtrials.org.cn (CTR20182110).


Assuntos
Neoplasias Colorretais , Neoplasias Gástricas , Humanos , Capecitabina/efeitos adversos , Equivalência Terapêutica , Neoplasias Gástricas/tratamento farmacológico , Estudos Cross-Over , Área Sob a Curva , Comprimidos , Jejum , China
20.
Eur J Pharm Biopharm ; 183: 102-111, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36632906

RESUMO

The model of core-shell structured tablets is gaining increased interest due to its advantages in controlled-release and combinational drug delivery. Through the encapsulation of the drug by the outer shell, this model exhibits huge potential for reduced administration frequency, improved taste-masking, and personalized medication strategy. Although different types of core-shell tablets have been recently developed, most of them focused on the embedding of the solid tablets. Therefore there is still a need to investigate an optimized model in which multiple dosage forms can be loaded. This work uses hot-melt extrusion and fused deposition modeling 3D printing (FDM 3DP) techniques to develop a multifunctional core-shell model for controlled drug delivery. Acetaminophen (APAP) was used as the model drug. Hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) was used as the matrix materials. Polyethylene oxide (PEO) and Eudragit RS PO (E RSPO) were used to adjust the printability while the E RSPO was expected to act as an extended-release agent due to its hydrophobicity. Liquid, semi-solid and solid dosage forms could be successfully loaded into the produced shells. The formulations were characterized by scanning electron microscopy, three point-bend tests, differential scanning calorimetry, and dissolution studies. The dissolution results suggested the modified-release character of the designed model. Overall, the designed core-shell model could be successfully produced via hot-melt extrusion paired with FDM 3DP techniques and could be utilized for the delivery of distinct dosage forms which improve the on-demand formulation development for patient-centered medication.


Assuntos
Sistemas de Liberação de Medicamentos , Tecnologia de Extrusão por Fusão a Quente , Humanos , Liberação Controlada de Fármacos , Comprimidos/química , Impressão Tridimensional , Tecnologia Farmacêutica/métodos
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