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2.
Medicine (Baltimore) ; 99(41): e22516, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031291

RESUMO

BACKGROUND: Xihuang pill, a famous traditional Chinese medicine formulation, is a broad-spectrum anti-tumor drug and has been widely used for the treatment of lung cancer in China. The aim of this study is to systematically investigate the efficacy and safety of Xihuang pill for the treatment of lung cancer. METHODS: We will perform the comprehensive literature search in the following databases from their inceptions to August 2020 for data extraction: PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, and Chinese Biomedical Literature Database. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.4 and Stata 16.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by I tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger test. The quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluate system (GRADE) system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of this study will provide evidence to show whether Xihuang pill is an effective intervention for patient with lung cancer. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/W2GHN.


Assuntos
Antineoplásicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Administração Oral , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Comprimidos
3.
Medicine (Baltimore) ; 99(37): e22065, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925741

RESUMO

BACKGROUND: Liuweiwuling (LWWL) tablet, a kind of plant-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatitis B virus-related cirrhosis (HBVC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy of LWWL tablet on biochemical and virological parameters, and quality of life (QoL) in patients with HBVC through the meta-analysis. METHODS: All available randomized controlled trials and high-quality prospective cohort studies that investigated the efficacy and safety of LWWL for patients with HBVC were searched from the following electronic databases: PubMed, Medline, Cochrane Library, Google Scholar, Web of Science, Excerpt Medica Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, China Scientific Journal Database, and Wanfang Database. Papers in Chinese or English published from January 2000 to August 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 authors. The clinical outcomes including biochemical (liver function and fibrosis indexes) and virological parameters, QoL, immune function and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data synthesis, sensitivity analysis, meta regression, subgroup analysis, and risk of bias assessment. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HBVC patients. CONCLUSION: Our study will draw an objective conclusion of the efficacy of LWWL on biochemical and virological parameters, and QoL in patients with HBVC. INPLASY REGISTRATION NUMBER: INPLASY202080010.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Metanálise como Assunto , Qualidade de Vida , Revisões Sistemáticas como Assunto , Medicamentos de Ervas Chinesas/efeitos adversos , Hepatite B/virologia , Humanos , Comprimidos , Resultado do Tratamento
4.
PLoS One ; 15(8): e0236297, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32780750

RESUMO

Naproxen is a widely used non-steroidal anti-inflammatory drug for the control of postoperative inflammatory signs and symptoms in dentistry. Its association with esomeprazole has been widely studied and has yielded good results for the control of acute pain, even with the delayed absorption of naproxen owing to the presence of esomeprazole. To further understand the absorption, distribution, and metabolism of this drug alone and in combination with esomeprazole, we will analyze the pharmacokinetic parameters of naproxen and its major metabolite, 6-O-desmethylnaproxen, in saliva samples. A rapid, sensitive, and selective liquid chromatography-tandem mass spectrometric method for the simultaneous determination of naproxen and 6-O-desmethylnaproxen in saliva will be developed and validated. Sequential saliva samples from six patients will be analyzed before and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6 8, 11, 24, 48, 72, and 96 h after the ingestion of one naproxen tablet (500 mg) and esomeprazole-associated naproxen tablets (500 + 20 mg), at two different times. After liquid-liquid extraction with ethyl acetate and HCl, the samples will be analyzed using an 8040 Triple Quadrupole Mass Spectrometer (Shimadzu, Kyoto, Japan). Separation of naproxen and its major metabolic products will be performed using a Shim-Pack XR-ODS 75Lx2.0 column and C18 pre-column (Shimadzu, Kyoto, Japan) at 40°C using a mixture of methanol and 10 mM ammonium acetate (70:30, v/v) with an injection flow of 0.3 mL/min. The total analytical run time will be 5 min. The detection and quantification of naproxen and its metabolite will be validated, which elucidate the pharmacokinetics of this drug, thereby contributing to its proper prescription for the medical and dental interventions that cause acute pain.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Monitoramento de Medicamentos/métodos , Esomeprazol/farmacocinética , Naproxeno/análogos & derivados , Saliva/química , Administração Oral , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Esomeprazol/administração & dosagem , Esomeprazol/isolamento & purificação , Feminino , Absorção Gastrointestinal , Humanos , Masculino , Metanol/química , Pessoa de Meia-Idade , Naproxeno/administração & dosagem , Naproxeno/isolamento & purificação , Naproxeno/farmacocinética , Dor Processual/tratamento farmacológico , Reprodutibilidade dos Testes , Comprimidos , Espectrometria de Massas em Tandem/métodos , Adulto Jovem
5.
Lancet HIV ; 7(8): e533-e544, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32763217

RESUMO

BACKGROUND: Paediatric dolutegravir doses approved by stringent regulatory authorities (SRAs) for children weighing 20 kg to less than 40 kg until recently required 25 mg and 10 mg film-coated tablets. These tablets are not readily available in low-resource settings where the burden of HIV is highest. We did nested pharmacokinetic substudies in patients enrolled in the ODYSSEY-trial to evaluate simplified dosing in children with HIV. METHODS: We did pharmacokinetic and safety substudies within the open-label, multicentre, randomised ODYSSEY trial (NCT02259127) of children with HIV starting treatment in four research centres in Uganda and Zimbabwe. Eligible children were randomised to dolutegravir in ODYSSEY and weighed 20 kg to less than 40 kg. In children weighing 20 kg to less than 25 kg, we assessed dolutegravir's pharmacokinetics in children given once daily 25 mg film-coated tablets (approved by the SRAs at the time of the study) in part one of the study, and 50 mg film-coated tablets (adult dose) or 30 mg dispersible tablets in part two of the study. In children weighing 25 kg to less than 40 kg, we also assessed dolutegravir pharmacokinetics within-subject on film-coated tablet doses of 25 mg or 35 mg once daily, which were approved by the SRAs for the children's weight band; then switched to 50 mg film-coated tablets once daily. Steady-state 24 h dolutegravir plasma concentration-time pharmacokinetic profiling was done in all enrolled children at baseline and 1, 2, 3, 4, 6, and 24 h after observed dolutegravir intake. Target dolutegravir trough concentrations (Ctrough) were based on reference adult pharmacokinetic data and safety was evaluated in all children in the corresponding weight bands who consented to pharmacokinetic studies and received the studied doses. FINDINGS: Between Sept 22, 2016, and May 31, 2018, we enrolled 62 black-African children aged from 6 years to younger than 18 years (84 pharmacokinetic-profiles). In children weighing 20 kg to less than 25 kg taking 25 mg film-coated tablets, the geometric mean (GM) Ctrough (coefficient of variation) was 0·32 mg/L (94%), which was 61% lower than the GM Ctrough of 0·83 mg/L (26%) in fasted adults on dolutegravir 50 mg once-daily; in children weighing 25 kg to less than 30 kg taking 25 mg film-coated tablets, the GM Ctrough was 0·39 mg/L (48%), which was 54% lower than the GM Ctrough in fasted adults; and in those 30 kg to less than 40 kg taking 35 mg film-coated tablets the GM Ctrough was 0·46 mg/L (63%), which was 45% lower than the GM Ctrough in fasted adults. On 50 mg film-coated tablets or 30 mg dispersible tablets, Ctrough was close to the adult reference (with similar estimates on the two formulations in children in the 20 to <25 kg weight band), with total exposure (area under the concentration-time curve from 0 h to 24 h) in between reference values in adults dosed once and twice daily, where safety data are reassuring, although maximum concentrations were higher in children weighing 20 kg to less than 25 kg than in the twice-daily adult reference. Over a 24-week follow-up period in 47 children on 30 mg dispersible tablets or 50 mg film-coated tablets, none of the three reported adverse events (cryptococcal meningitis, asymptomatic anaemia, and asymptomatic neutropenia) were considered related to dolutegravir. INTERPRETATION: Adult dolutegravir 50 mg film-coated tablets given once daily provide appropriate pharmacokinetic profiles in children weighing 20 kg or more, with no safety signal, allowing simplified practical dosing and rapid access to dolutegravir. These results informed the WHO 2019 dolutegravir paediatric dosing guidelines and have led to US Food and Drug Administration approval of adult dosing down to 20 kg. FUNDING: Paediatric European Network for Treatment of AIDS Foundation, ViiV Healthcare, UK Medical Research Council.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Adolescente , Peso Corporal , Criança , Relação Dose-Resposta a Droga , Feminino , Inibidores de Integrase de HIV/efeitos adversos , Inibidores de Integrase de HIV/farmacocinética , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Masculino , Comprimidos , Uganda , Zimbábue
6.
Yakugaku Zasshi ; 140(8): 1071-1080, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32741865

RESUMO

The purpose of the present study was to establish a novel method to evaluate water penetration rates by combining the local dynamic contact angle and thermographic approach to characterize water conduction properties in orally disintegrating (OD) tablets. The OD tablet tester OD-mate was used to measure the disintegration times of OD tablets. Other formulation characteristics, such as tablet hardness and friability, were evaluated. By examining three formulation characteristics, such as the disintegration time, tablet hardness, and friability, of 33 OD tablets for generic drugs, four characteristic OD tablets containing aripiprazole were selected. To quantitatively evaluate water penetration rates into the tablet interior, we measured the dynamic contact angle after dropping water locally on the tablet surface. Linearity with a high correlation coefficient was observed for each of the initial time-dependent changes in the dynamic contact angle. Water penetration rates into tablets were approximately twice as fast for Pharmaceuticals A and B than for Pharmaceuticals C and D. These rates were consistent with changes observed in tablet thermographic imaging. The relationship between the rapid disintegration of the tablet and its physical strength was discussed based on the internal structure of the tablet by X-ray CT and the additives of each OD tablet. The present results demonstrated that the water penetration rates of OD tablets, as measured by dynamic contact angle, may accurately detect differences in disintegration times in the human oral cavity.


Assuntos
Química Farmacêutica/métodos , Comprimidos , Termografia , Administração Oral , Fenômenos Químicos , Dureza , Solubilidade , Água
7.
J Chromatogr A ; 1626: 461388, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32797859

RESUMO

A reversed-phase high performance liquid chromatographic method was developed and validated for the simultaneous determination of the related substances of S-dapoxetine, including R-dapoxetine, (3S)-3-(dimethylamino-3-phenyl-1-propanol), S-3-amino-3-phenyl-1-propanol, 1-naphtol, 4-phenyl-2H,3H,4H-naphtho[1,2-b]pyran and 1-(2E)-Cinnamyloxynaphthalene. During the screening experiments seven different polysaccharide-type chiral stationary phases (amylose-based Lux-Amylose-1, Lux-i-Amylose-1 and Lux-Amylose-2, as well as cellulose-based Lux-Cellulose-1, Lux-Cellulose-2, Lux-Cellulose-3 and Lux-Cellulose-4) were tested in polar organic mode using a mobile phase consisting of 0.1% diethylamine in methanol, ethanol, 2-propanol and acetonitrile with 0.5 mL min-1 flow rate at 20 °C. Best results were obtained on Lux Cellulose-3 column with the ethanol-based mobile phase. To increase the retention factor of two, early-eluting impurities, water was added to the mobile phase. In order to counterbalance the increased total analysis time, higher column temperature (40 °C) and gradient elution, combined with flow-programming` was applied. Using the optimized conditions baseline separations were achieved for all compounds within 30 min. The method was validated according to the International Council on Harmonization guideline Q2(R1) and applied to the analysis of an approved, tablet formulation and dapoxetine-containing products sold on the internet. As expected, in the case of the pharmacy-acquired product, all of the monitored impurities were below 0.1%. However, interesting results were obtained when internet-acquired samples were analyzed. These tablets contained racemic dapoxetine and/or high concentration of R-dapoxetine impurity. Based on this work polysaccharide-based chiral stationary phases can be successfully applied for the simultaneous determination of achiral and chiral impurities in reversed-phase mode applying gradient elution and flow-rate programs. The study further underlines the importance of not only achiral, but also enantiomeric quality control, whenever counterfeiting of a single enantiomeric agent is suspected.


Assuntos
Benzilaminas/análise , Cromatografia Líquida de Alta Pressão/métodos , Naftalenos/análise , Cromatografia de Fase Reversa , Limite de Detecção , Espectrometria de Massas , Preparações Farmacêuticas/química , Estereoisomerismo , Comprimidos/química , Temperatura
8.
Ecotoxicol Environ Saf ; 204: 111066, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32781344

RESUMO

In this study, an iron-doped metal-organic framework (MOF) Fe/ZIF-8 was synthesized from ZIF-8 at room temperature. Direct carbonization of Fe/ZIF-8 under a nitrogen atmosphere produced nanoporous nitrogen doped carbon nanoparticles decorated with Fe component (Fe/NC). The Fe/NC exhibited a large surface area (1221.185 m2 g-1) and narrow pore-size distribution (3-5 nm). The nanoporous Fe/NC components along with Nafion were used to modify a glassy carbon electrode for the electrochemical determination of chloramphenicol and metronidazole via linear sweep voltammetry. Under optimal conditions, the reduction peak currents (observed at -0.237 V and -0.071 V vs. Ag/AgCl) of these analytes increased linearly with increasing chloramphenicol and metronidazole concentrations in the range of 0.1-100 µM and 0.5-30 µM, with the detection limits estimated to be 31 nM and 165 nM, respectively. This result was attributed to the large surface area, porous structure, high nitrogen content, and as well as the electrocatalytic effect of Fe atoms embeded in the carbon support. The proposed sensor was used for chloramphenicol and metronidazole analysis in samples, providing satisfactory results.


Assuntos
Carbono/química , Cloranfenicol/análise , Técnicas Eletroquímicas/métodos , Ferro/química , Estruturas Metalorgânicas/química , Metronidazol/análise , Nitrogênio/química , Animais , Cloranfenicol/urina , Eletrodos , Humanos , Limite de Detecção , Metronidazol/urina , Leite/química , Nanoporos , Soluções Oftálmicas/química , Porosidade , Comprimidos/química
9.
Medicine (Baltimore) ; 99(28): e20949, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664096

RESUMO

OBJECTIVES: Thalassemia is a hereditary disease, which caused economic burden in developing countries. This study evaluated the cost utility of new formulation of deferasirox (Jadenu) vs deferoxamine (Desferal) among B-Thalassemia-major patients from payer perspective in Iran. METHODS: An economic-evaluation through Markov model was performed. A systematic review was conducted in order to evaluate the clinical effectiveness of comparators. Because of chelating therapy is weight-dependent, patients were assumed to be 2 years-old at initiation in first and 18 years-old in second scenario, and model was estimated lifetime costs and utilities. Costs were calculated to the Iran healthcare system through payer perspective and measured effectiveness using quality-adjusted life years (QALYs). One-way sensitivity analysis and budget impact analysis was also employed. RESULTS: The 381 studies were retrieved from systematic searching through databases. After eliminating duplicate and irrelevant studies, 2 studies selected for evaluating the effectiveness. Jadenu was associated with an incremental cost-effectiveness ratio (ICER) of 1470.6 and 2544.7 US$ vs Desferal in first and second scenario respectively. The estimated ICER for Jadenu compared to generic deferoxamine was 2837.0 and 6924.1 US$ for first and second scenario respectively. For all scenarios Jadenu is presumed as cost-effective option based on calculated ICER which was lower than 1 gross domestic product per capita in Iran. Sensitivity analysis showed that different parameters except discount rate and indirect cost did not have impact on results. Based on budget impact analysis the estimated cost for patients using Desferal (based on the market share of brand) was 44,021,478 US$ in 3 years vs 42,452,606 US$ in replacing 33% of brand market share with Jadenu. This replacement corresponded to the cost saving of almost 1,568,872 US$ for the payers in 3 years. The calculated cost of using generic deferoxamine in all patients was 68,948,392 US$. The increase in the cost of using Jadenu for 10% of all patients in this scenario would be 934,427 US$ (1.36%) US$ at the first year. CONCLUSIONS: Based on this analysis, film-coated deferasirox appeared to be cost-effective treatment in comparison with Desferal for managing child and adult chronic iron overload in B-thalassemia major patients of Iran.


Assuntos
Análise Custo-Benefício , Deferasirox/administração & dosagem , Deferasirox/economia , Desferroxamina/administração & dosagem , Desferroxamina/economia , Quelantes de Ferro/administração & dosagem , Talassemia beta/tratamento farmacológico , Humanos , Irã (Geográfico) , Comprimidos/economia
10.
Int J Clin Pharmacol Ther ; 58(10): 583-594, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32716291

RESUMO

OBJECTIVES: To establish the relative bioavailability between a newly developed oral gel and a marketed oral lyophilisate-containing rizatriptan benzoate. MATERIALS AND METHODS: A total of 47 out of 48 healthy subjects, aged 34 ± 10 (SD) years and body mass index 24.7 ± 3.3 (SD) kg/m2 completed this single-center, open-label, randomized, 2-period cross-over trial with single-dose fasted administrations. Intake of both investigational products was separated by a washout period of at least 6 days. For pharmacokinetic evaluation, blood samples were withdrawn until 24 hours post dose. A validated liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was applied for the determination of rizatriptan in plasma. The lower limit of quantitation (LLOQ) was 0.100 ng/mL. Adverse events (AEs) were descriptively analyzed in the study population. Palatability of the new product was investigated based on a questionnaire. RESULTS: The geometric means of the parameters related with the extent of total exposure, i.e., AUC0-tlast and AUC0-∞, were 60.285 ng × h/mL and 60.865 ng × h/mL for test and 62.729 ng × h/mL and 63.312 ng × h/mL for reference, respectively. The geometric means of the peak exposure, i.e., Cmax, were 21.262 ng/mL for test and 21.447 ng/mL for reference. The point estimates (PEs) of the test/reference (T/R) adjusted geometric mean ratios of AUC0-tlast, Cmax, and AUC0-∞ (secondary parameter) were 96.11%, 99.12%, and 96.15%, respectively, and all of them showed 90% confidence intervals (CIs) within the range of 80.00 - 125.00% as suggested by regulatory requirements for bioequivalence assessment. In total, 13 subjects experienced 20 AEs during the trial; the most frequently reported AEs were headache (5 cases) and dizziness (3 cases). No AEs of severe intensity were reported. Palatability assessment of the new product provided sufficient data to discuss its acceptability. CONCLUSION: Bioequivalence was demonstrated in terms of rate and extent of absorption after administration of test and reference products. Concerning the safety evaluation, no negative implications on the possible use of the test formulation could be determined. Based on ratings by the subjects no relevant problem concerning acceptability of the new formulation in particular regarding taste and smell is to be expected.


Assuntos
Disponibilidade Biológica , Espectrometria de Massas em Tandem , Administração Oral , Adulto , Área Sob a Curva , Cromatografia Líquida , Estudos Cross-Over , Humanos , Comprimidos , Equivalência Terapêutica , Triazóis , Triptaminas , Adulto Jovem
11.
Int J Clin Pharmacol Ther ; 58(10): 575-582, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32729819

RESUMO

PURPOSE: Memantine is currently the only drug that acts on the glutamate energy system to treat Alzheimer's disease. A generic memantine tablet was developed to offer an alternative to the marketed tablet formulation. The purpose of this study was to assess the bioequivalence of two different memantine formulations among healthy male Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: We carried out single-center, randomized, single-dose, open-label, two-period, cross-over studies which including 20 healthy male Chinese subjects under fasting and fed conditions, respectively. Plasma samples were collected prior to and up to 240 hours after dosing. Key pharmacokinetic parameters including area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t), area from time zero to infinite (AUC0-∞), and Cmax were used for bioequivalence assessment. RESULTS: Under fasting condition, the 90% CIs of the geometric mean ratios of the test/reference drug for memantine were 106.5 - 114.0% for Cmax, 99.4 - 107.9% for AUC0-t, and 100.0 - 109.6% for AUC0-∞. Under fed condition, the 90% CIs of the geometric mean ratios of the test/reference drug for memantine were 94.8 - 104.3% for Cmax, 98.2 - 110.5% for AUC0-t, and 99.2 - 113.0% for AUC0-∞. CONCLUSION: The observed pharmacokinetic parameters of memantine of the test drug were similar to those of the reference formulation both in the fasting and fed state. That is to say, the test formulation of memantine 10-mg tablet is bioequivalent to the reference formulation (Ebixa 10-mg tablet).


Assuntos
Jejum , Área Sob a Curva , Estudos Cross-Over , Humanos , Masculino , Memantina , Comprimidos , Equivalência Terapêutica
12.
AAPS PharmSciTech ; 21(5): 182, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32613377

RESUMO

The aim of the present investigation was to formulate self-microemulsifying drug delivery system (SMEDDS) tablets to enhance the oral bioavailability of tizanidine hydrochloride. SMEDDS was prepared by using Capmul G as the oil phase, Tween 20 as the surfactant, and propylene glycol as the co-surfactant. The optimized formulation was characterized by dilution test, % transmittance, thermodynamic stability, dye solubility, assay, globule size, zeta potential, and TEM. A dye solubility test confirmed the formation of o/w microemulsion. Optimized formulation of SMEDDS had a drug content of 98 ± 0.75% (3.2± 0.3 mg) and droplet size of 96.61 ± 2.3 nm. Dilution and centrifugation tests indicated the physical stability of the formulation. The optimized SMEDDS was mixed with Neusilin as adsorbent, microcrystalline cellulose as diluent, and magnesium stearate as flow promoter, and compressed into tablets. The prepared tablets passed the tests of weight variation, hardness, friability, and assay. In vitro dissolution test indicated sustained release of tizanidine hydrochloride from the SMEDDS tablet for a period of 4 h. In vivo pharmacokinetic studies performed on male New Zealand rabbits showed a 4.61-fold increase in bioavailability compared with the marketed formulation. Thus, the developed SMEDDS tablet proved to be capable of enhancing oral bioavailability of tizanidine hydrochloride. Graphical abstract.


Assuntos
Clonidina/análogos & derivados , Emulsões/química , Administração Oral , Animais , Disponibilidade Biológica , Química Farmacêutica , Clonidina/administração & dosagem , Clonidina/química , Clonidina/farmacocinética , Técnicas In Vitro , Masculino , Coelhos , Solubilidade , Comprimidos
13.
Chemosphere ; 260: 127478, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32683022

RESUMO

Slow-releasing carbon source tablets were manufactured for an in-situ biological denitrification system. The average zero-order nitrate degradation rates seen, from highest to lowest, were in microcosms to which lactate, fumarate, propionate, and formate had been added. Fumarate was approximately 80% cheaper than lactate, and consequently was determined to be the most optimal slow-releasing carbon source in tablet form. The slow-releasing precipitating tablet (SRPT) and slow-releasing floating tablet (SRFT) were manufactured with hydroxypropyl methylcellulose (HPMC) as the agent of release control, microcrystalline cellulose pH 101 (MCC 101) as the binder, #8 sand as the precipitation agent, and calcium carbonate and citric acid as floating agents. Fourier transform infrared spectroscopy and powder X-ray diffraction indicated that the crystal arrangement in the SRPTs and SRFTs was maintained and ordered in a manner similar to raw excipients. SRFTs floated in water within 30 min and remained so for 5 d due to the buoyancy of carbon dioxide. The carbon source release rate was proportional to the quantity of HPMC added. The longevities of SRPT with 300 mg of HPMC and SRFT with 400 mg of HPMC were 25.4 d and 37.3 d, respectively. This study observed that SRPT and SRFT were manufactured effectively and are suitable for in-situ slow-releasing biological systems.


Assuntos
Desnitrificação , Água Subterrânea/química , Preparações de Ação Retardada , Excipientes/química , Derivados da Hipromelose , Nitratos , Pós , Solubilidade , Comprimidos , Água/química
15.
Paediatr Drugs ; 22(4): 369-383, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32507959

RESUMO

Desmopressin is a synthetic analogue of the natural antidiuretic hormone arginine vasopressin. Over the years, it has been clinically used to manage nocturnal polyuria in children with enuresis. Various pharmaceutical formulations of desmopressin have been commercialized for this indication-nasal spray, nasal drops, oral tablet and oral lyophilizate. Despite the fact that desmopressin is a frequently prescribed drug in children, its use and posology is based on limited pediatric data. This review provides an overview of the current pediatric pharmacological data related to the different desmopressin formulations, including their pharmacokinetics, pharmacodynamics and adverse events. Regarding the pharmacokinetics, a profound food effect on the oral bioavailability was demonstrated as well as different plasma concentration-time profiles (double absorption peak) of the desmopressin lyophilizate between adults and children. Literature about maturational differences in distribution, metabolism and excretion of desmopressin is rather limited. Regarding the pharmacodynamics, formulation/dose/food effect and predictors of response were evaluated. The lyophilizate is the preferred formulation, but the claimed bioequivalence in adults (200 µg tablet and 120 µg lyophilizate), could not be readily extrapolated to children. Prescribing the standard flat-dose regimen to the entire pediatric population might be insufficient to attain response to desmopressin treatment, whereby dosing schemes based on age and weight were proposed. Moreover, response to desmopressin is variable, whereby complete-, partial- and non-responders are reported. Different reasons were enumerated that might explain the difference in response rate to desmopressin observed: different pathophysiological mechanisms, bladder capacity and other predictive factors (i.e. breast feeding, familial history, compliance, sex, etc.). Also, the relapse rate of desmopressin treatment was high, rendering it necessary to use a pragmatic approach for the treatment of enuresis, whereby careful consideration of the position of desmopressin within this treatment is required. Regarding the safety of the different desmopressin formulations, the use of desmopressin was generally considered safe, but additional measures should be taken to prevent severe hyponatremia. To conclude the review, to date, major knowledge gaps in pediatric pharmacological aspects of the different desmopressin formulations still remain. Additional information should be collected about the clinical relevance of the double absorption peak, the food effect, the bioequivalence/therapeutic equivalence, the pediatric adapted dosing regimens, the study endpoints and the difference between performing studies at daytime or at nighttime. To fill in these gaps, additional well designed pharmacokinetic and pharmacodynamic studies in children should be performed.


Assuntos
Antidiuréticos/administração & dosagem , Desamino Arginina Vasopressina/administração & dosagem , Enurese/tratamento farmacológico , Antidiuréticos/farmacologia , Criança , Desamino Arginina Vasopressina/farmacologia , Humanos , Comprimidos
16.
Medicine (Baltimore) ; 99(22): e20374, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481421

RESUMO

BACKGROUND: Chronic atrophic gastritis (CAG) is defined as an important precancerous disease in the development of gastric cancer. Early intervention of CAG is of great significance in reducing symptoms and blocking its progression to gastric cancer. Weifuchun (WFC) tablet is a classic Chinese patent medicine used to treat CAG. However, there is no systematic review related to WFC for atrophic gastritis published in English. we will conduct systematic review and meta-analysis to provide more evidence on the effectiveness and safety for clinical use of WFC. METHODS AND ANALYSIS: Three English database and 4 Chinese databases will be searched from its inception to April 2020. Two trained researchers will independently select the qualified studies for data extraction and assess the quality and risk of bias. Then the meta-analyses will be performed by using the RevMan 5.2 and stata 14.0. The heterogeneity of data will be investigated by Cochrane X and I tests. Sensitivity analysis will be conducted to evaluate the stability of the results. A funnel plot analysis and Egger's test will be drawn to assess the publication bias. Finally, we will use the Grading of Recommendations Assessment, Development and Evaluate system to evaluate the methodological quality. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether WFC is an effective intervention for patient with CAG. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/2UTMB.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Gastrite Atrófica/tratamento farmacológico , Doença Crônica , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Comprimidos , Resultado do Tratamento
17.
Stud Health Technol Inform ; 270: 668-672, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32570467

RESUMO

It is crucial that registering the checklist needs to be done synchronously and according to the care tasks within the operating room. Therefore, we aim to find out what are the difficulties that the surgical technicians have when checking the list and exploring potential barriers to implementing the use of tablets. Qualitative research was conducted based on focus groups, in-depth interviews and on-site observations until a full coverage of the topics was achieved. We detected that this problem includes technical aspects (connectivity, hardware and software issues), those related to workflow and logistics, those related with registration process, and those related to organization culture and power structure. Based on results, we developed a plan to solve problems detected.


Assuntos
Lista de Checagem , Salas Cirúrgicas , Grupos Focais , Segurança do Paciente , Comprimidos
18.
Expert Opin Pharmacother ; 21(12): 1407-1418, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32486875

RESUMO

INTRODUCTION: Sufentanil is a selective µ-opioid agonist, used intravenously and intrathecally for moderate to severe acute pain. Sublingual sufentanil nanotablets have been developed; 15 mcg tablet for a patient-controlled analgesia device and 30-mcg tablet for a single-dose device administered by a healthcare professional. Dosing interval is a minimum of 20 min for a 15 mcg tablet and a treatment duration of up to 72 hours. The single 30-mcg nanotablet dosing interval is 1 hour. Mean plasma elimination half-life is 13 hours and bioavailability 47-57% after the first sublingual sufentanil tablet. AREAS COVERED: This review focuses on the effectiveness, safety, and feasibility of sublingual sufentanil 30-mcg single dose suspended by a healthcare professional for the management of moderate to severe acute pain. A few Phase 4 studies concerning the sublingual sufentanil tablet system containing 15-mcg nanotablets are also reviewed. EXPERT OPINION: Sufentanil sublingual 30-mcg nanotablets provide effective pain relief in various acute moderate to severe pain states. The safety profile of sublingual sufentanil 30 mcg is typical to opioids nausea, vomiting, and sedation being the most common ones. Sublingual sufentanil 30-mcg nanotablet has the potential for efficient moderate to severe pain management in supervised healthcare facilities.


Assuntos
Dor Aguda/tratamento farmacológico , Analgésicos Opioides/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Sufentanil/administração & dosagem , Dor Aguda/sangue , Administração Sublingual , Analgesia Controlada pelo Paciente , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Disponibilidade Biológica , Duração da Terapia , Feminino , Humanos , Náusea/induzido quimicamente , Medição da Dor , Dor Pós-Operatória/sangue , Sufentanil/efeitos adversos , Sufentanil/uso terapêutico , Comprimidos
19.
AAPS PharmSciTech ; 21(5): 172, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32533366

RESUMO

Dissolution testing and solubility determinations in different biorelevant media have gained considerable interest in the pharmaceutical industry from early-stage development of new products to forecasting bioequivalence. Among all biorelevant fluids, the preparation of fed-state simulated gastric fluid (FeSSGF) and handling of samples from dissolution/solubility testing in FeSSGF is considered to be relatively challenging. Challenges include maintaining the stability of FeSSGF medium upon sampling, filtration, and mitigating analytical interference of excipients and milk components. To overcome these challenges, standard and uniform working practices are required that are not only helpful in preparation of stable FeSSGF but also serve as a harmonizing guide for the collection of dissolution/solubility samples and their subsequent processing (i.e., handling and assay). The optimization of sample preparation methodology is crucial to reduce method-related variance by ensuring specificity, robustness, and reproducibility with acceptable recovery of the analytes. The sample preparation methodology includes a combination of techniques including filtration, solvent treatment, and centrifugation to remove the interfering media-related components and excipients from the analyte. The analytes of interest were chromatographically separated from the interfering analytes to quantify the drug concentration using the new high-performance liquid chromatography methods with ultraviolet detection. The methods developed allow rapid sample preparation, acceptable specificity, reproducible recoveries (greater than 95% of label claim), and quantification of study drugs (ibuprofen and ketoconazole). The sample preparation technique and method considerations provided here for ibuprofen and ketoconazole can serve as a starting point for solubility and dissolution testing of other small molecules in FeSSGF.


Assuntos
Desenvolvimento de Medicamentos/métodos , Ácido Gástrico/metabolismo , Ibuprofeno/metabolismo , Cetoconazol/metabolismo , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Antifúngicos/química , Antifúngicos/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Ibuprofeno/química , Cetoconazol/química , Reprodutibilidade dos Testes , Solubilidade , Comprimidos
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