RESUMO
OBJECTIVE To investigate the efficacy and safety of domestic Paliperidone extended-release tablets as a substitute for original Paliperidone extended-release tablets in the treatment of stable schizophrenia. METHODS A total of 65 patients with schizophrenia， who were treated with single original Paliperidone extended-release release tablets for 2 months or more in the outpatient or inpatient department of Shandong Daizhuang Hospital from June 2021 to June 2022， were collected and randomly divided into the domestic group （33 cases） and the original group （32 cases）. The domestic group was treated with the same dose of domestic Paliperidone extended-release tablets instead for 2 months， and the original group continued to use the previous dose of the original drug for 2 months. Positive and negative syndrome scale （PANSS） and treatment emergent symptom scale （TESS） were used to evaluate the two groups at the time of enrollment and the end of 1 week， 1 month and 2 months after enrollment. The incidence of ADR was calculated at the end of 2 months after enrollment. The fasting blood glucose， blood lipid indicators （triglyceride， total cholesterol， low-density lipoprotein， high-density lipoprotein， very-low-density lipoprotein）， serum prolactin levels， and paliperidone blood concentration were determined after the intravenous blood sample was collected. The ratio of paliperidone blood concentration to dose （C/D value） was calculated， and an electrocardiogram was performed. RESULTS There were 31 and 30 patients in the domestic group and the original group who completed the trial， respectively. There were no statistical significances in PANSS score， TESS score or C/D value at the time of enrollment and the end of 1 week， 1 month and 2 months after enrollment； there were no statistical significances in the levels of fasting blood glucose， blood lipid or serum prolactin at the time of enrollment and at the end of 2 months after enrollment （P＞0.05）. PANSS scores of both groups significantly decreased at the end of 1 month and 2 months after enrollment （P＜0.01）. The incidences of ADR were 25.81% in the domestic group and 30.00% in the original group， without significant difference （P＞0.05）， and there were no significant abnormalities in the electrocardiograms of the two groups. CONCLUSIONS Domestic Paliperidone extended-release tablets can directly replace the original tablets in the treatment of stable schizophrenia， and their clinical efficacy and safety are comparable.
RESUMO
Objective:To observe the effect of methylphenidate hydrochloride (MPH) combined with mentalization-based family therapy (MBFT) on clinical efficacy and social function in children with attention deficit hyperactivity disorder (ADHD).Methods:Sixty-four children with ADHD diagnosed in Wuxi Children's Hospital and Affiliated Hospital of Jiangnan University from June 2019 to May 2021 were selected and divided into observation group ( n=32) and control group ( n=32) according to the random number table.Children in both groups received methylphenidate hydrochloride extended-release tablets, while those in the observation group were given additional MBFT.The duration of treatment was 12 weeks in both groups.The parent symptom questionnaire (PSQ), swanson nolan and pelham-version Ⅳ (SNAP-Ⅳ) parent Al scale, and Weiss impairment functional scale (WFIRS-P) were used to evaluate the effectiveness of treatment.Statistical analysis was performed by SPSS 25.0 statistical software.In particular, the χ2 test was used for counting data and the paired sample t test was used for comparison of measurement data between the two groups before and after treatment. Results:(1) All the PSQ dimension scores of patients in the observation group and the control group after treatment were significantly lower than those before treatment (all P<0.01). Compared with the control group after treatment, the PSQ dimension scores of personality and behavior problems ((1.25±0.15), (0.94±0.18), t=7.484, P<0.001), learning problems ((1.57±0.16), (1.32±0.20), t=5.522, P<0.001), psychosomatic disorders ((0.56±0.11), (0.44±0.13), t=3.986, P<0.001), impulse hyperactivity ((1.76±0.23), (1.54±0.25), t=3.663, P<0.001), anxiety ((0.94±0.12), (0.76±0.11), t=6.255, P<0.001) and hyperactivity index ((1.74±0.19), (1.51±0.16), t=5.238, P<0.001) decreased significantly in the observation group after treatment.(2) Compared with the pre-treatment period, the SNAP-Ⅳ scale scores of attention deficit, impulsivity-hyperactivity and oppositional defiance were significantly lower in both groups after treatment (all P<0.01); and compared with the control group, the SNAP-Ⅳ scale scores of the above three dimensions were significantly lower in the observation group (all P<0.01). (3) All six dimensions (family, learning and school, life skills, self-management, social activities, and risk-taking activities)of the WFIRS-P scale were significantly lower in the children in the observation group after treatment compared with those before treatment (all P<0.01), and all the six dimensions of the WFIRS-P scale were significantly lower in the observation group compared with those in the control group (all P<0.01). Conclusion:Methylphenidate hydrochloride extended-release tablets combined with MBFT can significantly improve the clinical symptoms and social function of children with ADHD.
RESUMO
Aryloxypropanolamine is an essential structural scaffold for a variety of β-adrenergic receptor antago-nists such as metoprolol. Molecules with such a structural motif tend to degrade into α, β-hydroxypropanolamine impurities via a radical-initiated oxidation pathway. These impurities are typically polar and nonchromophoric, and are thus often overlooked using traditional reversed phase chromatography and UV detection. In this work, stress testing of metoprolol confirmed the generation of 3-isopropylamino-1,2-propanediol as a degradation product, which is a specified impurity of metoprolol in the European Pharmacopoeia (impurity N). To ensure the safety and quality of metoprolol drug products, hydrophilic interaction chromatography (HILIC) methods using Halo Penta HILIC column (150 mm×4.6 mm, 5 μm) coupled with charged aerosol detection (CAD) were developed and optimized for the separation and quantitation of metoprolol impurity N in metoprolol drug products including metoprolol tartrate injection, metoprolol tartrate tablets, and metoprolol succinate extended-release tablets. These HILIC-CAD methods were validated per USP validation guidelines with respect to speci-ficity, linearity, accuracy, and precision, and have been successfully applied to determine impurity N in metoprolol drug products.
RESUMO
Objective To study the clinical effect and safety of paliperidone extended-release tablets in the treatment of schizophrenia.Methods 80 patients with schizophrenia were selected as the research subjects .Accord-ing to randomized single blind,the patients were divided into two groups ,40 cases in each group.The control group was given risperidone treatment,the observation group used paliperidone extended-release tablets treatment.The total effective rate,positive and negative symptoms score (PANSS score),mental disability score (WHO-DAS score II) and the incidence of adverse reactions were compared between the two groups .Results The clinical total effective rate (95.00%) in the observation group was significantly higher than the control group (80.00%,χ2 =4.114,P <0.05).After treatment, the PANSS score and WHO-DAS II score in the observation group were significantly decreased compared with before treatment (t =8.002,7.761,all P <0.05),which were lower than those in the control group after treatment (t =4.114,3.702,all P <0.05).The incidence rate of adverse reaction between the two groups had no statistically significant difference (7.50% vs.10.00%,χ2 =0.157,P >0.05).Conclusion The clinical efficacy of paliperidone extended-release tablets in the treatment of schizophrenia is significant ,which can effectively relieve patients with mental disorders ,and it is safe and reliable.
RESUMO
Objective To compare the sustained-release tablets paliperidone and risperidone tablets starting glycolipid metabolism in female patients with schizophrenia.Methods Eighty-five cases of women treated in our hospital episode schizophrenia patients were randomly divided into observation group (42 cases) and control group (43 cases).were treated with sustained-release tablets paliperidone and risperidone tablets monotherapy two months.Measuring body mass index before and after treatment (BMI),waist circumference (waist),triglyceride (TG),high density lipoprotein (HDL),fasting plasma glucose (FPG),2 h glucose after OGTT (2 h PG),Positive and Negative Syndrome scale (PANSS) for efficacy evaluation.Results Comparison minutes before treatment PANSS total score and factors,the difference was not statistically significant.After treatment,PANSS total score and factor scores,the difference was not statistically significant.Compared with the previous treatment,both groups PANSS total score and factor scores were significantly decreased after treatment,the difference was statistically significant (P ＜ 0.05).Two groups of patients before treatment indexes,the difference was not statistically significant.After treatment in the control group TG,former TC,HDLC,LDLC,BMI,and waist circumference with treatment,the difference was statistically significant (P ＜ 0.05);the observation group BMI and waist circumference compared with before treatment,the difference was statistically significant (P ＜ 0.05).After observation group TG,TC,LDLC,BMI and waist circumference were significantly lower than the control group,HDLC significantly higher,the difference was statistically significant (P ＜ 0.05).Two FPG,2hPG,SBP and DBP,the difference was not statistically significant (P ＞ 0.05).Adverse reactions in patients in the observation group were significantly lower than the control group,the difference was statistically significant (P ＜ 0.05).Conclusion The sustained-release tablets paliperidone and risperidone female first-episode schizophrenia patients have the same effect,but paliperidone extended release tablets in female patients improve blood lipids,BMI and waist circumference is superior to risperidone.
RESUMO
Objective:To optimize the clinical dosage regimen of amoxicillin and clavulanate potassium extended release ( ER) tablets based on the PK/PD parameters. Methods:Totally 30 healthy subjects ( half male and half female) were randomly divided into three groups, and orally administered the ER tablets respectively under fasting condition, before the meal and after the meal, and the optimal administration time was determined by comparing the pharmacokinetic characteristics. The subjects in the three groups were ad-ministered the ER tablets respectively at low, medium and high dosage, and the optimal dosage and dosing interval were determined based on the PK/PD parameters. Results:Under fasting condition, the AUC of amoxicillin [(32.2 ±15.0) μg·h·ml-1] was sig-nificantly lower than that before the meal [(41.7 ±1.92) μg·h·ml-1] and that after the meal [(42.6 ±17.7) μg·h·ml-1]. In contrast, the AUC of clavulanate acid after the meal [(1.89 ±0.54) μg·h·ml-1] was significantly lower than that under fasting condition [(2.55 ±0.76) μg·h·ml-1] and that before the meal [(2.58 ±0.76) μg·h·ml-1] (P MIC) in 12 h was 5. 5, 7 and 10 h, and the percentage was 46%, 58% and 83%, respectively, and T> MIC in 12 h was 4. 5, 6 and 8 h, and the percentage was 38%, 50% and 67%, re-spectively when MIC was 4. 0μg·ml-1 . Conclusion:It is suggested that amoxicillin and clavulanate potassium ER tablets be taken at the start of a standard meal, 2 tablets per time, twice daily, which is sufficient to achieve T> MIC of 40% -50%.
RESUMO
Objective:To investigate the curative effect and prognosis of schizophrenia patients treated with paliperidone extended -release tablets.Methods:Totally 72 cases of patients with schizophrenia were divided into the observation group (n=35) and the control group ( n=37 ) according to the order of admission .The obsevation group was treated with paliperidone extended-release tab-lets, while the controll group was treated with risperidone tablets , and both groups were treated for 8 weeks.The positive and negative syndrome scale(PANSS) was used to assess the effect of the two groups , the social function defect scale (SDSS) and prognosis of the two groups were compared.Results: After the 2-week treatment, the PANSS score, positive symptom score, negative symptom score and general symptom score were all decreased in the two groups when compared with those before the treatment (P<0.05),and the scores in the observation group were lower than those in the controll group (P<0.05).After the treatment, the SDSS was significantly reduced in the two groups when compared with that before the treatment (P<0.05), and the reduction in the observation group was more notable than that in the control group (P<0.05).The total effective rate of the observation group was 94.3%, which was higher than that (67.6%) of the control group (P<0.05).The incidence of adverse reactions, such as anxiety and akathisia, and the total adverse drug reactions in the observation group were both lower than those in the control group (P<0.05).Conclusion:Paliperidone extended-release tablets can effectively relieve suffering from schizophrenia with quick effect , few adverse reactions , high safety and good effect , which is worthy of promotion in clinical use .
RESUMO
Objective To establish and validate the assay methods of release,content,content uniformity and related sub?stances of desvenlafaxine succinate (DVS) in extended-release tablets. Methods The ultraviolet spectrophotometric method was used to determine the DVS release from DVS extended-release tablets. The content uniformity,content and related substance were deter?mined by high-performance liquid chromatography(HPLC). To validate all the method,we respectively examined specificity,linearity, recovery rate,precision and stability,etc. Results The results showed that the analysis method for release was specific,the calibra?tion curve was linear in the range of 10-200μg/ml,and all the recovery,repeatability and intermediate precision met requirements. The method for detection of content and content uniformity was specific and linear in the range of 5-400μg/ml,the recovery,repeat?ability and intermediate precision met requirements. The method for related substances was specific and sensitive ,the linear and recovery rate met the requirements. All of the solutions were stable during 24 h at room temperature. Conclusion The analysis meth?od for release is simple,sensitive,specific and accurate,the method for content and content uniformity is accurate and reliable,and the method for related substances is specific,sensitive and accurate. These methods are suitable for quality control of DVS extended-release tablets.
RESUMO
Objective To establish and validate the assay methods of release, content, content uniformity and related substances of desvenlafaxine succinate (DVS) in extended- release tablets. Methods The ultraviolet spectrophotometric method was used to determine the DVS release from DVS extended-release tablets. The content uniformity, content and related substance were determined by high-performance liquid chromatography (HPLC). To validate all the method, we respectively examined specificity, linearity, recovery rate, precision and stability, etc. Results The results showed that the analysis method for release was specific, the calibration curve was linear in the range of 10-200 µg/ml, and all the recovery, repeatability and intermediate precision met requirements. The method for detection of content and content uniformity was specific and linear in the range of 5-400 µg/ml, the recovery, repeatability and intermediate precision met requirements. The method for related substances was specific and sensitive, the linear and recovery rate met the requirements. All of the solutions were stable during 24 h at room temperature. Conclusion The analysis method for release is simple, sensitive, specific and accurate, the method for content and content uniformity is accurate and reliable, and the method for related substances is specific, sensitive and accurate. These methods are suitable for quality control of DVS extendedrelease tablets.
RESUMO
Objective:To establish the drug release determination conditions and method for phencynonate hydrochloride extended release tablets. Methods:The drug release of the tablets was determined by HPLC using a Diamonsil C18 (250 mm × 4. 6 mm, 5 μm) column with the mobile phase of acetonitrile-water-phosphoric acid-triethylamine (270∶400∶1. 3∶2), the detection wavelength was 220 nm, the flow rate was 1. 0 ml·min-1 , the column temperature was 30 ℃ and the injection volume was 20 μl. The effects of different release apparatus, release media and rotation speeds on the release of phencynonate hydrochloride extended-release tablets were studied as well. Results:The established drug release determination method had a good linear relationship within the range of 0. 3-5. 0 μg· ml-1(r=0. 999 8), and the average recovery was 100. 6%(RSD=1. 16%, n=15). Under the conditions of 900ml pH 3. 0 phos-phate buffer solution as the release medium, rotation speed of 50 r·min-1 and the settlement basket as the apparatus, the release be-havior of the product was complied with a zero-level model in vitro, and the release equation was as follows:Q=6. 141 2t-9. 328 7(r=0. 996). Conclusion:The method is simple, accurate and reliable, and suitable for the quality control of phencynonate hydrochlo-ride extended-release tablets.
RESUMO
A dissolution test for fesoterodine low dose extended-release tablets using liquid chromato-graphic (LC) method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature (40 1C) using a mobile phase of acetonitrile:methanol:0.03 M ammonium acetate (pH 3.8) (30:15:55, v/v/v), run at a flow rate of 1.5 mL/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2 (paddle) at 100 rpm and 900 mL of phosphate buffer at pH 6.8 as the dissolution medium. Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.
RESUMO
Objective:To compare the dissolution results of doxazosin mesylate extended release tablets determined by a fiber-optic method and the imported drug registration standard method. Methods:The drug release process was determined directly with a FODT-601 fiber-optic medicine dissolution/ release rate process monitoring system. Aqueous solution of hydrochloric acid and sodium chloride was used as the dissolution medium, the paddle rotation rate was 75 r·min-1 , the detection wavelength was set at 246 nm while the reference wavelength was 550 nm. The detection length was 5 mm. Results:The standard curve of doxazosin mesylate was linear within the concentration range of 0. 468 1-11. 700 0μg·ml-1 and r values were greater than 0. 999 0. The intra-and inter-day RSD (n=6) was 1. 6% and 2. 0%, respectively. The recovery of doxazosin mesylate was 99. 0% and RSD was 1. 4(n=9). The results determined by the fiber-optic method were generally higher than those determined by the standard method, and there were some differences in the measurement results. Conclusion:Fiber-optic method shows the whole dissolution process objectively. It is particularly prominent in the research on the dissolution of rapid, extended and controlled release preparations. However, it can not replace the standard method yet.
RESUMO
Objective To assess the efficacy and safety of fluvastatin sodium extended-release tablets (fluvastatin XL) 80 mg once daily compared to fluvastatin sodium immediate-release capsules (fluvastatin IR) 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk.Methods In this multi-center,randomized,double-blind,double-dummy,active-controlled,parallel-group study,after 6-week open-label treatment with fluvastatin IR 40 mg once daily,patients who did not reach their lipid goals were randomized to 12-week double-blind treatment with fluvastatin XL 80 mg once daily or fluvastatin IR 40 mg twice daily.Results (1) There were 218 patients enrolled in each group.At the study endpoint,no statistical difference was found in the mean percent change from baseline for LDL-C with-8.69％ [from (3.504 ±0.060) mmol/L to (3.153 ±0.065) mmol/L] in the fluvastatin XL group and-7.89％ [from (3.491 ±0.050) mmol/L to (3.181 ±0.060) mmol/L] in the fluvastatin IR group (P ＞ 0.05).The 95％ CI for difference between the two groups in adjusted mean percent change from baseline was (-4.70％-3.09％),which was within the pre-specified non-inferiority margin.In the fluvastatin XL group,the proportion of patients with moderate cardiovascular(CV) risk and high CV risk achieving their LDL-C treatment goals at endpoint was 50.0％ and 31.5％ respectively,while the proportion was 42.5％ and 24.5％ respectively in the fluvastatin IR group.No significant difference was found between the two groups in the proportion of patients who reached their lipid goals and the changes from baseline with other lipid parameters.(2)Similar safety profiles were observed in the two treatment groups,with 21.1％ adverse event (AE) (8.3％ study-drug related AE) in the fluvastatin XL group and 17.0％ AE (6.3％ study-drug related AE) in the fluvastatin IR group.Conclusion The efficacy of fluvastatin XL 80 mg once daily is comparable to fluvastatin IR 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk and both treatments are safe and well-tolerated.
RESUMO
Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE) can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm) software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm) software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed.
A reprodutibilidade do processo de fabricação de comprimidos e o controle das suas propriedades farmacotécnicas depende da otimização dos aspectos de formulação e dos parâmetros de processo. O planejamento de experimentos como o Desenho de Experimentos (DOE) pode ser utilizado para acelerar a produção desta formulação, em particular, para a obtenção de comprimidos de liberação prolongada. Formulações de bromoprida são comercializadas sob a forma de péletes de liberação prolongada, o que torna o produto caro e de difícil fabricação. O objetivo deste estudo foi preparar novas formulações de bromoprida de liberação prolongada na forma de comprimidos e desenvolver modelos matemáticos visando ao escalonamento destas formulações, controlando o peso e a dureza dos comprimidos durante a fabricação, de acordo com a 34ª Edição da USP. Estudos de DOE foram realizados utilizando o software Minitab(tm). Diferentes combinações de excipientes foram avaliadas visando à obtenção dos comprimidos de liberação prolongada de bromoprida. No estudo de scale-up, coletaram-se e mediu-se a influência das variações nos parâmetros da máquina de compressão. Processaram-se os dados obtidos pelo software Minitab (tm), gerando equações matemáticas aptas para a previsão do comportamento de compactação do pó em escala industrial. Os comprimidos obtidos apresentavam características adequadas em termos de liberação sustentada, sendo a cinética de liberação estabelecida utilizando modelos matemáticos, indicando que esta formulação pode ser uma substituta aos péletes de bromoprida atualmente comercializados.
Assuntos
Comprimidos/análise , Antieméticos/análise , Projetos de Pesquisa , Cinética , Escalas de PreparaçãoRESUMO
The aim of this work is to present the two one-sided test (TOST) as an alternative approach to compare dissolution profiles of extended-release dosage forms. The dissolution profiles of oxycodone extended-release tablets containing 10 mg, 20 mg and 40 mg (reference and generic) were evaluated according to the requirements described in United States Pharmacopeia. These dissolution profiles were compared using the conventional similarity factor (f2) and the proposed TOST as an equivalence test. TOST is a simple and alternative approach to compare dissolution profiles of extended-release dosage forms. It allows us to identify the time-point (or time-points) that did not show similarity. We concluded that the two one-sided test performed at a significance level of 5% and defined as D = 10 showed results comparable to those obtained by the conventional similarity factor (f2).
O objetivo deste trabalho é apresentar o teste uni-caudal duplo (TOST) como uma abordagem alternativa na comparação do perfil de dissolução de formas farmacêuticas de liberação prolongada. Os perfis de dissolução de comprimidos de liberação prolongada de oxicodona contendo 10 mg, 20 mg e 40 mg (genérico e referência) foram avaliados de acordo com os requisitos descritos na Farmacopeia Americana. Estes perfis de dissolução foram comparados empregando-se o fator de semelhança convencional (f2) e o método TOST como teste de equivalência. TOST é uma abordagem simples e alternativa para a comparação de perfis de dissolução de formas farmacêuticas de liberação prolongada. Este permite identificar o ponto (ou pontos) que não apresentou semelhança. Considerando-se D = 10, concluímos que o teste uni-caudal duplo num nível de significância de 5% apresenta resultados comparáveis àqueles obtidos com o fator de semelhança convencional (f2).
Assuntos
Formas de Dosagem/normas , Dissolução , Habilidades para Realização de Testes/métodos , Comprimidos/classificação , Equivalência TerapêuticaRESUMO
OBJECTIVE:To establish a HPLC method for determining the content of fluvastatin sodium in fluvastatin sodium extended-release tablets. METHODS:An Agilent SB-C18 column was used and the mobile phase was CH3CN-0.1% phosphate acid, 50∶50. Flow rate was 1mL?min-1, wavelength was 234nm and the sample size was 20?L. RESULTS:The fluvastatin sodium concentration had good liner relationship from 4.84～96.8?g?mL-1(r=0.999 9), and the average recovery was 100.1%,RSD=0.9%. CONCLUSION:This method was simple, fast, accurate, and precise, could be used to determine content in fluvastatin sodium extended-release tablets.
RESUMO
AIM: To achieve an optimum manufacturing process for acetaminophen extended release tablets. METHODS: To evaluate and set the manufacturing process according to the compressibility of the granule and the dissolubility of the finished tablets. RESULTS & CONCLUSION: The results showed that the bi-layer tablet technology was the most preferable pro- cess. The in vitro dissolution behavior and the in vivo bioavailability of the tablets are comparable to those of the imported products from McNEIL Consumer Healtheare Co. USA.