Quantitative relationship between physical activity and antihypertensives in elderly women / Relación cuantitativa entre actividad física y antihipertensivos en ancianas / Relação quantitativa entre atividade física e anti-hipertensivos em idosas

ABSTRACT Introduction: Physical activity is an important tool to manage systemic arterial hypertension. However, less is known about the relationship of physical activity with the number of antihypertensive drugs used by older adults. Objective: The aim of this study was to compare the number of antihypertensive drugs used by older female adults (aged ≥ 60 years) with a low level of physical activity with the number used by those with a high level of physical activity, and to verify how many participants used more than two antihypertensive drugs. Methods: Twenty-eight physically active older women with systemic arterial hypertension who participated in a physical activity program for community-dwelling older female adults were divided into two groups: participants who presented lower habitual physical activity levels were placed in group 1 and participants that presented higher habitual physical activity levels were placed in group 2, according to the Baecke questionnaire. In addition, the number of antihypertensive drugs used by participants was collected. Results: The number of prescribed antihypertensive drugs was 2.0 (median) for both groups investigated. There was no significant difference between groups regarding the number of antihypertensive tablets prescribed (p>0.05). Although there was no statistical difference, a higher proportion of participants from the lower physical activity group used more than two antihypertensive drugs. Conclusion: The level of habitual physical activity did not affect the number of antihypertensive tablets used by hypertensive elderly women. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMEN Introducción: La actividad física es una herramienta importante para el manejo de la hipertensión arterial sistémica. Sin embargo, se sabe poco sobre la relación de la actividad física con la cantidad de medicamentos antihipertensivos utilizados por las ancianas. Objetivo: El objetivo de este estudio fue hacer una comparación entre el número de medicamentos antihipertensivos utilizados por mujeres adultas mayores (≥ 60 años) y bajo nivel de actividad física con el número utilizado por aquellas con alto nivel de actividad física, y verificar cuántas de las participantes usaron más de dos medicamentos antihipertensivos. Métodos: Veintiocho ancianas físicamente activas con hipertensión arterial sistémica que participaron en un programa de actividad física para mujeres adultas mayores residentes en la comunidad fueran divididas en dos grupos: las participantes que presentaron niveles más bajos de actividad física habitual se ubicaron en el grupo 1 y las participantes que presentaron los mayores niveles de actividad física se ubicaron en el grupo 2, según el cuestionario de Baecke. Además, se recogió el número de medicamentos antihipertensivos utilizados por las participantes. Resultados: El número de comprimidos antihipertensivos prescritos fue de 2,0 (mediana) para ambos grupos investigados. No hubo diferencia significativa entre los grupos en cuanto al número de medicamentos antihipertensivos prescritos (p>0,05). Aunque no hubo diferencia estadística, una mayor proporción de participantes del grupo de menor actividad física usó más de dos medicamentos antihipertensivos. Conclusión: El nivel de actividad física habitual no afectó el número de comprimidos antihipertensivos utilizados por las ancianas hipertensas. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

RESUMO Introdução: A atividade física é uma importante ferramenta no manejo da hipertensão arterial sistêmica. No entanto, pouco se sabe sobre a relação entre a atividade física e a quantidade de anti-hipertensivos usados por idosos. Objetivo: O objetivo deste estudo foi realizar uma comparação entre o número de anti-hipertensivos usados por idosas (≥ 60 anos) com baixo nível de atividade física com o número usado por aquelas com alto nível de atividade física, verificando quantas participantes usaram mais de dois anti-hipertensivos. Métodos: Vinte e oito idosas fisicamente ativas com hipertensão arterial sistêmica que participavam de um programa de atividade física para idosas da comunidade foram divididas em dois grupos: as participantes que apresentaram níveis mais baixos de atividade física habitual foram colocadas no grupo 1 e as participantes que apresentaram maiores níveis de atividade física foram colocados no grupo 2, de acordo com o questionário de Baecke. Ademais, coletou-se o número de medicamentos anti-hipertensivos utilizados pelas participantes. Resultados: O número de fármacos anti-hipertensivos prescritos foi de 2,0 (mediana) para ambos os grupos investigados. Não houve diferença significativa entre os grupos quanto ao número de comprimidos anti-hipertensivos prescritos (p>0,05). Embora não tenha havido diferença estatística, uma maior proporção de participantes entre o grupo de menor atividade física utilizava mais de dois anti-hipertensivos. Conclusão: O nível de atividade física habitual não afetou a quantidade de comprimidos anti-hipertensivos utilizados pelas idosas hipertensas. Nível de evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.

Preparation and pharmacokinetics of flumazenil sublingual tablet / 药学实践杂志

Objective To prepare flumazenil sublingual tablets and study its bioavailability. Methods Flumazenil sublingual tablets were prepared by compressing flumazenil inclusion compound with hydroxypropyl-β-cyclodextrin as the inclusion material. In a double-cycle crossover trial, twelve beagle dogs were randomly divided into two groups, one group receiving flumazenil sublingual tablets and the other receiving flumazenil injections. LC-MS method was developed and validated to determine flumazenil plasma concentration. The pharmacokinetic parameters and bioavailability were calculated using WinNonlin pharmacokinetic software. Results In the pharmacokinetic study, AUClast of flumazenil injection and sublingual tablet was （8.41±2.15） and （8.86±2.83） h·ng·ml−1, respectively; Cmax was （10.96±2.62） and （6.36±2.14） ng/ml, respectively; tmax was （0.18±0.05） and （0.58±0.24） h, respectively. The bioavailability of flumazenil sublingual tablet was 52.68%. Conclusion Clathrates were used to prepare flumazenil sublingual tablets to achieve safe and efficient delivery. LC-MS method was established for the determination of flumazenil plasma concentration, and the advantages were simple, accurate and sensitive.

Preparation and quality evaluation of Eriodictyol chewable tablet / 中国药房

OBJECTIVE To prepare the Eriodictyol chewable tablet and to evaluate its quality. METHODS The chewable tablet was prepared by the wetting granulation method by using microcrystalline cellulose （MCC） and mannitol as fillers， polyvinylpyrrolidone （PVP） as adhesive， citric acid and sucralose as flavor correction agents， magnesium stearate as lubricant. The comprehensive evaluation was conducted on Eriodictyol chewable tablets with the dosage of each excipient as a factor using the appearance， taste， flavor and texture as indicators. The ratio of excipients was optimized by orthogonal test， and the quality of Eriodictyol chewable tablets prepared by optimized formulation was evaluated in terms of appearance， weight difference， hardness， fragility， eriodictyol content， dissolution and content uniformity. RESULTS The optimal formulation was as follows： 26.4% eriodictyol （50 mg each piece）， 45% mannitol， 25% MCC， 0.3% citric acid， 0.3% sucralose， 1% magnesium stearate， 2% PVP （preparing 5% solution using purified water）. The scores of 3 batches of Eriodictyol chewable tablets in the validation test were 8.76， 8.75 and 8.80 （RSD＝0.30%， n＝3）， respectively. The Eriodictyol chewable tablet had a complete appearance and a smooth surface； the average tablet weight was 192.57 mg， the average hardness was 57.36 N， the fragility was 0.09%， the average content of eriodictyol per tablet was 50.74 mg， the cumulative dissolution within 30 min was exceeding 80%， and the content uniformity was 5.51. CONCLUSIONS Eriodictyol chewable tablet prepared by optimal formulation conforms to the requirements of the 2020 edition of Chinese Pharmacopoeia.

Preparation and evaluation of sirolimus sustained release tablets based on mesoporous silicon loaded self-microemulsion / 药学学报

Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the Cmax of the sustained-release tablets decreased by 49.47%, the Tmax of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.

ffects of Zuogui Pills on kidney-yin deficiency syndrome of premature ovarian insufficiency rats / 国际中医中药杂志

Objective:To study the effects of Zuogui Pills on rats with kidney-yin deficiency syndrome of premature ovarian insufficiency.Methods:Totally 40 SD female unmated rats were randomly divided into blank group, model group, Zuogui Pills group and Bujiale group, with 10 rats in each group. Except for blank group, rats in other groups were subcutaneously injected with ZP3 and gavaged with levothyroxine sodium to induce kidney-yin deficiency syndrome model of premature ovarian insufficiency. At the same time of modeling, Zuogui Pills group and Bujiale group received corresponding drugs for gavage, and the other groups received corresponding solvent for gavage, once a day, for consecutive 21 days. On day 0, 7, 14 and 21, ear temperature and body weight of rats were measured, and the ovarian index, uterus index and thyroid index were calculated. Serum levels of adenosine cyclic phosphate (cAMP), cyclic guanosine phosphate (cGMP), Cortisol, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E 2) were detected by ELISA. Pathological changes of ovary was observed with HE staining. Results:On day 14 and 21, compared with model group, the body weight of rats in Zuogui Pills group increased ( P<0.05), and the ear temperature decreased ( P<0.05); compared with model group, the ovarian index, uterine index and thyroid index of rats in Zuogui Pills group decreased ( P<0.05), the levels of serum cAMP/cGMP, cortisol, FSH and LH decreased ( P<0.05), and the level of E 2 increased ( P<0.05). Conclusion:Zuogui Pills have certain improvement effect on rats with kidney-yin deficiency syndrome induced by levothyroxine sodium tablets combined with ZP3.

Analysis on mechanisms of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstones and cholecystitis based on network pharmacology / 国际中医中药杂志

Objective:To analyze the mechanism of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstone and cholecystitis based on network pharmacology; To conduct a comparative analysis.Methods:The chemical components of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid and their drug targets were collected from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). DAVID 6.8 database was used to search for the associated diseases of the drug targets. The disease targets of gallstone and cholecystitis were collected from GeneCards and other databases. The protein-protein interactions network was established based on the intersecting targets of three drugs and two diseases. KEGG enrichment analysis was performed based on the DAVID 6.8 database. Cytoscape 3.7.1 software was used to construct a complex network and topology analysis of component- target- disease between three drugs and diseases.Results:222 chemical components and 3 133 drug targets were collected for Jindan Tablets. 104 chemical components and 1 425 action targets were collected for Xiaoyan Lidan Tablets. 1 chemical component and 119 action targets were collected for ursodeoxycholic acid. The three drugs were associated with 31 diseases. 1 382 disease targets for gallstones and cholecystitis were collected. There were 237, 163 and 33 targets for gallstones and cholecystitis in the three drugs, of which 17 were shared by the three drugs and 20 were shared by Jindan Tablets and Xiaoyan Lidan Tablets. Based on the DAVID database, 113, 74 and 10 significant KEGG enrichment pathways were obtained for the three drugs respectively.Conclusions:The three drugs shared many targets and pathways in the treatment of gallstones and cholecystitis, which all had the function of regulating metabolism and inhibiting inflammatory response, while participating in apoptosis, oxidative stress and cancer pathology process. However, they had their own special effects, with Jindan Tablets favoring involving in the cancer process and inhibition of inflammation, and promoting angiogenesis. Xiaoyan Lidan Tablets and ursodeoxycholic acid focused on regulating cholesterol metabolism, and Xiaoyan Lidan Tablets also regulated steroid metabolism and inhibit inflammation, while ursodeoxycholic acid regulated bile acid metabolism.

Studies on orally disintegrating tablet of diphenhydramine hydrochloride and caffeine / 药学实践杂志

Objective To optimize the formulation and preparation of diphenhydramine hydrochloride and caffeine orally disintegrating tablet. Methods Melt granulation technology of steric acid and API was used to mask the unpleasant tasting of diphenhydramine hydrochloride. The tablets were prepared by direct pressing the dry powder with CCMC-Na as disintegrating agent. The formulation was optimized by orthogonal experiments to achieve the shortest disintegration time and the best taste correction. Results The optimized formula of orally disintegrating tablet was as follows： diphenhydramine hydrochloride 25 mg, caffeine 60 mg, stearic acid 25 mg, aspatan 40 mg, blueberry essence 7 mg, mannitol 45 mg, MCC 210 mg, CCMC-NA 25 mg, SDS 8 mg and magnesium stearate 5 mg. Conclusion This preparation method for orally disintegrating tablet of diphenhydramine hydrochloride and caffeine is practical and easy for quality control.

Miao medicinal crossbow acupuncture therapy as adjuvant treatment for lung cancer pain: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of Miao medicinal crossbow acupuncture therapy as adjuvant treatment for lung cancer pain based on oxycodone hydrochloride extended-release tablet.@*METHODS@#A total of 60 patients with lung cancer pain were randomized into an observation group (30 cases, 1 case dropped off) and a control group (30 cases). In the control group, oxycodone hydrochloride extended-release tablet was given orally, 10 mg a time, once every 12 hours. On the basis of the treatment in the control group, Miao medicinal crossbow acupuncture therapy was applied once every other day in the observation group. The treatment of 14 days was required in the two groups. Before and after treatment, the numerical rating scale (NRS) score, number of break-out pain and Karnofsky performance status (KPS) score were observed in the two groups. The equivalent oxycodone consumption and rate of adverse reactions were recorded, the analgesic effect was evaluated in the two groups.@*RESULTS@#Compared before treatment, the NRS scores and number of break-out pain were decreased while the KPS scores were increased after treatment in the two groups (P<0.01). After treatment, the NRS score and number of break-out pain in the observation group were lower than the control group (P<0.01), the KPS score in the observation group was higher than the control group (P<0.05). The equivalent oxycodone consumption of whole course and the rate of adverse reactions i.e. constipation, drowsiness, nausea and vomiting in the observation group were lower than the control group (P<0.05). The analgesic effect rate was 93.1% (27/29) in the observation group, which was superior to 63.3% (19/30) in the control group (P<0.05).@*CONCLUSION@#On the basis of oxycodone hydrochloride extended-release tablet, Miao medicinal crossbow acupuncture therapy as adjuvant treatment can effectively relieve the pain degree, reduce the number of break-out pain and improve the health status and quality of life in patients with lung cancer pain, enhance the efficacy of medication and reduce its adverse reactions.

Tiaoshen Jieyu acupuncture combined with sertraline hydrochloride tablet for post-stoke depression: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between Tiaoshen Jieyu acupuncture (acupuncture for regulating mind and relieving depression) combined with sertraline hydrochloride tablet and simple sertraline hydrochloride tablet for post-stroke depression (PSD).@*METHODS@#A total of 76 patients with PSD were randomized into an observation group (38 cases, 6 cases dropped off) and a control group (38 cases, 4 cases dropped off). Both groups were treated with conventional treatment i.e. controlling blood pressure and anti-inflammation. Sertraline hydrochloride tablet was given orally in the control group, 20 mg a time, once a day. On the basis of the treatment in the control group, Tiaoshen Jieyu acupuncture was applied at Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6), Taichong (LR 3), etc. in the observation group, Baihui (GV 20) and Yintang (GV 24+) were connected to electroacupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 30 min a time, once a day, 6 times a week. Treatment of 8 weeks was required in both groups. Before and after treatment, the scores of Hamilton depression scale (HAMD), National Institutes of Health stroke scale (NIHSS), Barthel index (BI) and Pittsburgh sleep quality index (PSQI) were observed respectively, the therapeutic efficacy and rate of adverse reactions were evaluated in the two groups.@*RESULTS@#After treatment, the scores of HAMD, NIHSS and PSQI were lower while BI scores were higher than those before treatment in both groups (P<0.05); the scores of HAMD, NIHSS and PSQI in the observation group were lower while BI score was higher than those in the control group (P<0.05). The total effective rate was 93.8% (30/32) in the observation group, which was higher than 70.6% (24/34) in the control group (P<0.05). The rate of adverse reactions was 9.4% (3/32) in the observation group, which was lower than 32.4% (11/34) in the control group (P<0.05).@*CONCLUSION@#Tiaoshen Jieyu acupuncture combined with sertraline hydrochloride tablet can improve the depression degree, neurological function, activity of daily living and sleep quality in patients with post-stroke depression, the clinical efficacy is superior to simple sertraline hydrochloride, and can alleviate the adverse reactions caused by medication.

Research of the mechanism of Huganning tablet in the treatment of nonalcoholic fatty liver disease based on network pharmacology and computer-aided drug design / 药学学报

In this study, we explored the mechanism of Huganning tablet (HGNP) in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology and computer-aided drug design. Firstly, the potential ingredients and targets of HGNP were identified from TCMSP database, Swiss Target Prediction database, Chinese pharmacopoeia (2015) and literatures, and then the targets of HGNP intersected with NAFLD disease targets that obtained in GeneCards database to acquired potential targets. The bioconductor bioinformatics package of R software was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The network of “potential ingredient-key target-pathway” was formed in Cytoscape software to study the interactions between potential ingredients of HGNP, key targets, pathways and NAFLD. Based on the results of network pharmacology, the molecular docking analysis of the key targets and potential active ingredients in HGNP tablets with top degree in the network was conducted using Discovery Studio 2020 software, followed by molecular dynamics simulations, binding free energy calculation, drug-likeness properties analysis and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties prediction. In vitro, HepG2 cells were used to establish steatosis model, and the effects of five key compounds on hepatocyte steatosis were analyzed by oil red O staining and triglyceride (TG) content determination. The results showed that 141 ingredients and 151 potential targets were obtained. A total of 2 526 items and 151 pathways were identified by GO and KEGG enrichment analysis. The molecular docking suggested that five components, isorhamnetin, salvianolic acid B, emodin, resveratrol and rhein, exhibited strong binding ability with key targets [retinoic acid receptor RXR-alpha (RXRA), tumor necrosis factor (TNF), glycogen synthase kinase-3 beta (GSK3B), serine/threonine-protein kinase 1 (AKT1)]. It was further verified that isorhamnetin and salvianolic acid B bind to key targets with good structural stability and binding affinity based on molecular dynamics simulations and binding free energy calculations. The drug-likeness properties, pharmacokinetic properties and toxicity of five key compounds were more comprehensively analyzed through drug-likeness properties analysis and ADMET properties prediction. In vitro, all five compounds, isorhamnetin, salvianolic acid B, emodin, resveratrol, and rhein, improved hepatocyte steatosis of HepG2 cells, confirming the reliability of the present study. In conclusion, based on network pharmacology, computer-aided drug design and in vitro validation, this study investigated the mechanism of HGNP for the treatment of NAFLD at multiple levels and provided a basis for its clinical application.

Guanxinning Tablet and their active substances alleviate ox-LDL-induced endothelial cell injury / 药学学报

This study investigated the intervention effect of Guanxinning Tablet on human umbilical vein endothelial cells (HUVECs) injury induced by oxidized low density lipoprotein (ox-LDL), providing experimental basis for Guanxinning Tablet in the treatment of atherosclerosis-related diseases. Under the damage of HUVECs by ox-LDL, the cell viability was detected by CCK-8 (cell counting kit-8) assay; lactate dehydrogenase (LDH) in the cell culture supernatant was detected by the corresponding kit; the cell morphology of different groups was observed by common phase contrast microscope; reactive oxygen species (ROS) and NO levels in the cells were detected by DCFH-DA and DAF-FM DA probes, respectively; monocyte adhesion assay was used to detect the recruitment of THP-1 in HUVECs, and TMRM dye was used to detect the level of mitochondrial membrane potential; interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) secretion in the cells was detected by ELISA assay. The results showed that Guanxinning Tablet had a concentration-dependent proliferative effect on HUVECs. Under the stimulation of 100 μg·mL-1 ox-LDL, the morphology of endothelial cells was significantly changed. At this time, NO level was significantly decreased, ROS level was significantly increased and accompanied by a decrease in mitochondrial membrane potential. The recruitment of THP-1 cells by endothelial cells and IL-6, ICAM-1 and MCP-1 were also significantly increased, resulting in oxidative stress and inflammatory injury. Guanxinning Tablet and its composed extracts could significantly improve cell morphology, increase NO level, decrease ROS production, and also reduce the secretion of inflammation-related proteins IL-6 and MCP-1. Salvia miltiorrhiza and Ligusticum striatum DC. have significant synergistic effects on NO. Among them, salvianolic acid B and salvianic acid A exerted the main effects, and the combined efficacy of salvianic acid A and ferulic acid was superior to that of single administration. The above results showed that Guanxinning Tablet and their active substances had the effects of improving endothelial basal function, resisting oxidative stress, and alleviating inflammatory injury, and Salvia miltiorrhiza and Ligusticum striatum DC. synergized, which may be related to their regulation of oxidative stress and inflammation and have application prospects in the treatment of atherosclerosis-related diseases.

Management of Pre-Operative Anxiety Through Ayurveda Drug- Case Series

Anxiety can be defined as unpleasant subjective sense due to dread over something unlikely to happen, such as standing at the point of death. It is mostly accompanied by physical symptoms i.e. restlessness, fatigue, problems in concentration, and muscular tension. So, in nutshell, Perioperative anxiety is vague, uneasy feeling, the source of which is often nonspecific and unknown to the individual but known to cause abnormal hemodynamics as a consequence of sympathetic, parasympathetic and endocrine stimulation. Thus causes more difficultly in general management during operative and postoperative period. This case series is comprised of three case of pre-operative anxiety which was posted for planned ano-rectal surgeries. At the time of hospital admission, level of anxiety was quite normal in all the patients, but by lapsing time and operative period come nearer they were feeling moderate to high level of anxiety due to various individual triggering reasons. For its management, Bramhyadi tablet (500 mg) was given in 2 doses- A night before OT, at morning on day of OT along with counselling. Here, preoperative anxiety was assessed by The Amsterdam preoperative anxiety and information scale, Hamilton anxiety rating, vital parameters and overall interview with patient in 5 phases: 1- At time of admission, 2- A night before OT, 3- At morning on day of OT, 4-1 hour after OT, 5-24 Hour after OT. Mental calmness, reduction in associated physical symptoms and stability in vital parameter were suggested positive influence of Bramhyadi tablet and counselling

EVALUATION OF EFFECT OF EXPIRED TABLET ON SOIL PHYSICAL PROPERTIES: A CASE STUDY OF RANOZEX TABLET

Pharmaceutical waste can result from many locations and from many activities in health care facilities. They generate medicines waste which are compounding from pharmacy. In the present study, an attempt has been made to know the effect of Ranozex expired tablet on soil physical quality. The expired tablets were applied at a concentration of 150 mg, 250 mg, 500 mg, 750 mg and 1g. The expired ranozex tablets was mixed with sandy loam clay soil and kept for observation for 7 to 27 days respectively. The experimental setup was maintained till 27 days, at every 7 days intervals, the soil was extracted and subjected to selected physical properties such as bulk density, particle density, water holding capacity and moisture content. From the results, it was found that, the bulk density and particle density were found to be reduced. The percentage of water holding capacity was found to be higher during the experimental period

Optimization of Diltiazem hydrochloride osmotic formulation using QBD approach

Abstract Diltiazem hydrochloride (DLH) is a calcium channel blocker useful for the treatment of angina pectoris, arrhythmia, and hypertension. DLH having a short half-life needs frequent administration for successful treatment but this poses a problem of poor patient compliance. These requirements are served by elementary osmotic pump tablets (EOP) based controlled-release (CR) systems. Quality by design (QbD) approach assists in screening various factors with subsequent assessment of critical parameters that can have a major impact on the scalability of EOP. Tablets were formulated using wet granulation method followed by osmotic coating. Factorial design based QbD strategy aided in defining the risk assessment of influential variables such as hydrophilic polymers and osmotic coat component on the in-vitro release kinetics of the designed EOP tablets. These formulated EOP systems followed zero-order kinetics, a characteristic feature of EOPs. EOP tablets were formulated applying a systematic QbD statistical approach. The formulated DLH EOP systems with improved concentration-independent behavior helped to address the challenges of IR formulation. Application of QbD strategy in ascertaining the scalability of DLH EOP formulation would help pharmaceutical industries in the translation of EOP based drug delivery systems from R&D to market.

Optimization and Quest of HPMC loaded Stavudine Controlled Release Dosage Development by Central Composite Design utilizing Reduced Factorial Screening Technique

Abstract The current research focused on screening and finding the significant independent variables in stavudine loaded tablet, followed by optimizing the best formulation using central composite design. The objective of the study to develop stavudine loaded controlled release tablet utilizing reduced factorial design, followed by optimization technique as well as characterization of prepared tablets. Preliminary trial batches were prepared using different grades of hydroxypropyl methylcellulose. The resolution-IV reduced factorial design was selected to screen the significant independent variables in the dosage form design. A total number of eight runs were prepared and responses were recorded. The signified factors identified by half-normal and Pareto chart. The prepared tablets are evaluated for various physiochemical characterizations. Three dependent responses such as hardness, dissolution at 6 hour and 12 hours are considered in optimization process. Later on, drug-polymer interaction study was carried out. The principal of the study design based on finding the best formulation with prefixed set parameter values utilizing the concept of screening technique. It observed that HPMC K15M (57.18 %), HPMC K100 (66.32 %) and PVP K30 (7.97 %) as best composition in a formulation batch would fulfill the predetermined parameter with specific values.

Optimization of the Extragranular Excipient Composition of Paracetamol Tablet formulation using the Quality by Design Approach

Abstract The purpose of this study is to optimize the composition of extragranular excipients (EGE) and mixing time of granules with EGE of paracetamol tablet formulation using Design of Experiments (DoE) approach. The effect of the composition of EGE and the mixing time of granules with EGE on granule and tableting properties of paracetamol tablet formulation was investigated using a combined model of mixture and process factors (Design-Expert 12). A total of 18 tablet formulations were manufactured by wet granulation using varying compositions of EGE and varying mixing time. Granule and tablet properties of each formulation were evaluated as response variables for the design, data generated were fitted into models and analysed to generate a design space that was used for optimization studies. The proposed EGE composition as predicted by the design was confirmed and validated after preparation and evaluation of the granule and tablet properties. The optimized composition for the EGE that yielded granules and tablets of desirable characteristics was found to be maize starch (5 %), talc (4.9 %) and magnesium stearate (0.1 %) with a mixing time of 2 min. The tablets produced with the optimized composition had better mechanical strength and disintegration time than the formulation prepared using an existing formula of maize starch (7.8 %), talc (2 %) and magnesium stearate (0.2 %) that were obtained using the One Variable at a Time (OVAT) approach. This study confirmed the relevance of quality by design in development of pharmaceutical formulations.

Optimization of HPLC method using central composite design for estimation of Torsemide and Eplerenone in tablet dosage form

Abstract A simple, precise, accurate and robust high performance liquid chromatographic method has been developed for simultaneous estimation of Torsemide and Eplerenone in tablet dosage form. Design of experiment was applied for multivariate optimization of the experimental conditions of RP-HPLC method. A Central composite design was used to study the response surface methodology and to analyse in detail the effects of these independent factors on responses. Total eleven experiments along with 3 center points were performed. Two factors were selected to design the matrix, one factor is variation in ratio of Acetonitrile and the second factor is flow rate (mL/min). Optimization in chromatographic conditions was achieved by applying Central composite design. The optimized and predicted data from contour diagram comprised mobile phase (acetonitrile, water and methanol in the ratio of 50: 30: 20 v/v/v respectively), at a flow rate of 1.0 ml/min and at ambient column temperature. Using these optimum conditions baseline separation of both drugs with good resolution and run time of less than 5 minutes were achieved. The optimized assay conditions were validated as per the ICH guidelines (2005). Hence, the results showed that the Quality by design approach could successfully optimize RP-HPLC method for simultaneous estimation of Torsemide and Eplerenone.

Sustained release matrix tablet of 100 mg losartan potassium: Formulation development and in vitro characterization

Abstract Sustained release matrix tablets of 100 mg losartan potassium HCl were fabricated with two release retarding polymers namely HPMC K100 M and affinisol by direct compression method. Nine trial formulations were prepared by varying content of these polymers, each from 50 mg to 100 mg; keeping the total weight of the tablet 310 mg. The best formulation was selected based on in vitro drug release profile for 12 hours conducted in Type II dissolution apparatus at 50 rpm and water as dissolution medium. Pre-compression parameters such as bulk density, tap density, Carr's index and Hausner ratio were evaluated for the selected tablet. The tablets were subjected to thickness, weight variation test, drug content, hardness and friability. Drug release kinetics, surface morphology and accelerated stability study were investigated for that selected formulation. Formulation F4 with the composition of 75 mg HPMC K100M and 100 mg affinisol was selected as the best formulation that extended the drug release up to 12 hours. Pre-compression parameters and other tableting properties were within the Pharmacopoeia limit. Release kinetics analysis proved non-fickian zero-order drug release and that was further confirmed by surface morphology of the tablets before and after dissolution study visualized by SEM. The developed formulation was found to be stable for one month stored at 60 ○C.

In Vitro Evaluation of Dalbergia sissoo and Acacia modesta gum as Pharmaceutical Binders for Drug Delivery System

Abstract The present study aimed to compare the crude, modified and hydrolyzed gums of Dalbergia sissoo and Acacia modesta as a biodegradable binder for drug delivery system using acetaminophen as a model drug. The physiochemical properties such as pH, fluorescence analysis and swelling index were determined. The gums were hydrolyzed and modified. Acetaminophen tablets were prepared using wet granulation technique and the gum solutions were used as a binder. Hydroxypropyl methylcellulose was used as a synthetic binder. Different properties of granules and tablets were evaluated. Results showed that both gums were acidic in nature, while D. sissoo and A. modesta showed light brown and creamy color in fluorescence analysis. The swelling ratio was the highest in water followed by 0.1N HCl and least in phosphate buffer. The prepared tablets showed faster and slower dissolution profiles in the same dissolution system. The crude gums have the highest dissolution rate, and this rate was decreased in the case of modified and hydrolyzed gums samples. The crude gums showing slower release can be useful in sustained-release tablets, while the modified gums having faster release rate are helpful in conventional tablet formulation. Taken together, the selected gums could be a good model for evaluation as a binder or hydrophilic polymer in tablet formulation.

Effect of Haikunshenxi capsule combined with losartan potassium tablets on renal function and inflammatory factors in patients with chronic kidney disease / 中国医师进修杂志

Objective:To investigate the curative effect of Haikunshenxi capsule combined with losartan potassium tablets on chronic kidney disease (CKD) and its effect on renal function and inflammatory factors.Methods:One hundred patients with chronic kidney disease in Shaoxing Central Hospital from January 2018 to December 2019 were selected and randomly divided into observation group (50 cases) and control group (50 cases). The control group was treated with losartan potassium tablets based on conventional therapy, and the observation group was treated with Haikunshenxi capsulebase on control group. The treatment course of the two groups was 12 weeks. The curative effect, renal function, inflammatory factors, 24h urinary protein (24 h Upro) and glomerular filtration rate (GFR) were compared between the two groups before and after treatment.Results:The total effective rate in the observation group was higher than that in the control group: 90.0%(45/50) vs. 72.0%(36/50), χ2 = 5.26, P<0.05. After treatment, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in the two groups were decreased and the levels of Scr and BUN in the observation group were lower than those in the control group: (63.27 ± 2.89) μmol/L vs. (67.89 ± 2.35) μmol/L, (5.23 ± 0.19) mmol/L vs. (5.56 ± 0.16) mmol/L, the differences were statistically significant ( P<0.05). After treatment, the levels of serum C-reactive protein (CRP) , interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the two groups were decreased and the levels of CRP, IL-6 and TNF-α in the observation group were lower than those in the control group: (2.97 ± 0.34) mg/L vs. (3.58 ± 0.42) mg/L, (3.64 ± 0.68) ng/L vs. (4.97 ± 0.96) ng/L, (14.32 ± 2.17) ng/L vs. (17.86 ± 2.06) ng/L, the differences were statistically significant ( P<0.05). After treatment, the level of 24 h Upro in two groups was decreased, while the level of GFR was increased, and the level of 24 h Upro in the observation group was lower than that in the control group: (0.87 ± 0.09) g vs. (1.15 ± 0.13) g , but the level of GFR in the observation group was higher than that in the control group: (101.73 ± 3.12) ml/(min·m 2) vs. (96.75 ± 2.35) ml/(min·m 2), the differences were statistically significant ( P<0.05). Conclusions:Haikunshenxi capsule combined with losartan potassium tablets has obvious curative effect on patients with chronic kidney disease, and can improve renal function and micro inflammation.