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“Drug Release Kinetic Modeling and Gamma Scintigraphic Studies of Dual Ca2+ and SO4 2- Cross-linked Microbeads for Colon Specific Targeting” 结肠特异性靶向双Ca2+和SO4 2-交联微珠的药物释放动力学建模和伽马闪烁成像研究
IF 0.4 Pub Date : 2020-11-28 DOI: 10.22377/ajp.v14i4.3835
S. Lanjhiyana
Objectives: Ionic gelation-based polyelectrolyte complexes of blend chitosan-sodium alginate polysaccharides based microbeads of methotrexate were prepared by dual cross-linkages with divalent Ca2+ and SO4 -2 ions for colon targeting. Materials and Methods: Those developed dual cross-linked formulations were characterized for particle size, entrapment studies, drug content, swelling degree, etc. Results: The surface morphology results showed that the optimized formulations were semi-spherical and rough-surfaced. The in vitro drug release carried out in various simulated fluids at various pH had shown lesser release profiles in acidic media as compared to alkaline media at the end of 24 h studies. A significant drug release (P > 0.05) was observed in colonic fluids containing 2 and 4% w/v rat cecal as compared with control. In vivo targeting ability for the colon-specific region was established through gamma scintigraphic imaging technique. Differential scanning calorimetry and X-ray diffraction analysis further confirms for semi-crystalline and complete cross-linking state. The release profile and mathematical kinetic modeling revealed for anomalous non-Fickian type formulations were best fitted with Higuchi and Hixson-Crowell model, respectively. Conclusion: It can be concluded that the optimized formulations may be effective for colon targeting and promising to achieve drug targeting for colorectal cancer.
目的:通过与二价Ca2+和SO4 -2离子的双交键法制备甲壳聚糖-海藻酸钠多糖甲氨蝶呤微球的离子凝胶型多电解质复合物,用于结肠靶向。材料与方法:对所研制的双交联制剂进行了粒径、包封研究、药物含量、溶胀度等表征。结果:表面形貌结果表明,优化后的配方为半球形,表面粗糙。在24小时研究结束时,在不同pH值的各种模拟流体中进行的体外药物释放显示,酸性介质中的释放曲线比碱性介质中的释放曲线要小。与对照组相比,含有2%和4% w/v的结肠液中药物释放显著(P < 0.05)。通过伽玛闪烁成像技术建立了结肠特异性区域的体内靶向能力。差示扫描量热法和x射线衍射分析进一步证实了半结晶和完全交联状态。异常非fickian型配方的释放曲线和数学动力学模型分别适合于Higuchi和Hixson-Crowell模型。结论:优化后的制剂具有结肠靶向性,有望实现大肠癌药物靶向治疗。
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引用次数: 0
Determination of Rate of Release of Dye from the Hydrogels using Spectrophotometer Studies 用分光光度计研究测定水凝胶中染料的释放速率
IF 0.4 Pub Date : 2020-11-28 DOI: 10.22377/ajp.v14i4.3817
S. Iqubal
Introduction: The main aim of the research was to determine the rate of release of dye from the hydrogels using spectrophotometer studies. Materials and Methods: The gelatin (GE)-polyethylene glycol (PEG) composite hydrogels were prepared by the simultaneous method. Several combinations of GE-PEG composite hydrogels were prepared with methylene blue (MB) dye in it. The components were thoroughly mixed by stirring the solution during preparation to make them homogeneous. Results and Discussion: The effects of glutaraldehyde, GE, and PEG variation on dye release with different hydrogel composition samples investigated. The results showed that as the concentration of cross-linking agent increases from 5 ml to 15 ml, absorbance of the sample decreased from 0.43 to 0.42 in demineralized water and 0.47 to 0.42 in 0.1M HCl due to decrease in the pore diameter of the sample, and with increased GE composition from 2.0 g to 4.0 g, absorbance of the sample also increased. Conclusion: The increased amount of GE decreased the intactness of the matrix, allowing the greater release of MB. The hydrophilic nature of PEG increases the interaction with the solvent which causes swelling of the microvoids, thus resulting in the high release of MB.
引言:本研究的主要目的是使用分光光度计研究确定染料从水凝胶中的释放速率。材料与方法:采用同步法制备明胶-聚乙二醇复合水凝胶。以亚甲基蓝(MB)染料为原料,制备了几种GE-PEG复合水凝胶。在制备过程中,通过搅拌溶液将各组分充分混合,使其均匀。结果与讨论:研究了不同水凝胶组成样品中戊二醛、GE和PEG的变化对染料释放的影响。结果表明,当交联剂的浓度从5ml增加到15ml时,由于样品的孔径减小,样品在软化水中的吸光度从0.43降低到0.42,在0.1M HCl中的吸光度从0.45降低到0.42%,并且随着GE组成从2.0g增加到4.0g,样品的吸光度也增加。结论:GE用量的增加降低了基质的完整性,使MB得到更大的释放。PEG的亲水性增加了与溶剂的相互作用,导致微孔膨胀,从而导致MB的高释放。
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引用次数: 1
A Predictive In vitro Biorelevant Dissolution Method Development for Fluvoxamine Extended-Release Capsules by Simulating Preprandial and Postprandial In vivo Performance 氟伏沙明缓释胶囊体外生物相关溶出度预测方法的建立
IF 0.4 Pub Date : 2020-11-28 DOI: 10.22377/ajp.v14i4.3820
Devi Thamizhanban
Aims: This research work was about biorelevant dissolution method development for fluvoxamine extended-release capsule by correlating preprandial and postprandial in vivo performance. Materials and Methods: The mean plasma concentration profile obtained after oral administration of extended-release capsules was deconvoluted using Wagner-Nelson deconvolution technique, to achieve percentage fraction of drug absorbed, and target dissolution profile was derived. Biorelevant dissolution method was developed using USP Apparatus-3, with dissolution media simulating gastrointestinal tract sink condition. A full factorial design of experiment was carried out for optimizing dissolution volume and dips per minutes, to achieve target dissolution profile. Results: The dissolution results observed using office of generic drugs recommend dissolution method were not comparable with target dissolution profile and observed with F2 value of 37 at preprandial and 43 at postprandial condition. The achieved dissolution profile was comparable with target and observed with F2 value of 81 at preprandial condition and 85 at postprandial condition. Conclusion: The developed dissolution method establishes good correlation between in vitro drug release and in vivo drug absorption and observed with R2 value of 0.998 at preprandial condition and 0.997 at postprandial condition. The method gives the advantage of giving biowaiver.
目的:本研究通过关联餐前和餐后体内表现,开发氟伏沙明缓释胶囊的生物相关溶出方法。材料和方法:使用Wagner-Nelson去卷积技术对口服缓释胶囊后获得的平均血浆浓度曲线进行去卷积,以获得药物吸收的百分比分数,并导出目标溶出度曲线。使用USP Apparatus-3开发了生物相关溶出方法,溶出介质模拟胃肠道水槽条件。为了优化溶解体积和每分钟浸渍量,进行了全因子实验设计,以实现目标溶解曲线。结果:使用仿制药办公室推荐的溶出方法观察到的溶出结果与目标溶出曲线不可比较,餐前F2值为37,餐后F2值为43。所获得的溶出曲线与目标相当,并且在餐前条件下观察到F2值为81,在餐后条件下观察得到F2值为85。结论:所建立的溶出度方法在体外药物释放和体内药物吸收之间建立了良好的相关性,在餐前条件下R2值为0.998,在餐后条件下R2为0.997。该方法具有生物豁免的优点。
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引用次数: 0
Formulation Development, Characterization, and Evaluation of Controlled Nasal Drug Delivery Systems for Cefuroxime Axetil 头孢呋辛酯鼻腔给药系统的配方开发、表征和评价
IF 0.4 Pub Date : 2020-11-28 DOI: 10.22377/AJP.V14I4.3830
S. Rajarajan
Objective: This current study objective is to develop cefuroxime axetil (CA) nasal mucoadhesive microspheres for an alternative utilization of dosage form for respiratory tract infections Materials and Methods: CA microspheres were prepared by modified emulsion-lyophilization method in which chitosan and beta-cyclodextrin were used as a release retardant polymer. The model is optimization by 24 factorial designs and validated using ANOVA. CA microspheres evaluated for entrapment efficiency, ex vivo mucoadhesion and % drug release. The optimized formulations were performed for its Fourier transform infrared (FT-IR) analysis, particle size and polydispersity index (PDI) and zeta potential, thermal analysis DSC and XRD, and surface morphology by scanning electron microscopy followed by in vitro and ex vivo release kinetic studies. Key Findings: Results of these evaluations showed that entrapment efficiency was found to be 69.21–80.45%, particle size in the range of 12.55–17.22 μm, mucoadhesion in the range of 72.51–79.68%, and drug release in the range of 72.21–83.65%. FT-IR studies ensured that no drug-polymer interaction in the formulated microspheres. PDI and zeta potential were measured and the mean particle size and distribution of microspheres were in the range and the surface topography revealed a spherical surface for all the formulations and a round cavity enclosed by an outer shell composed of the drug and polymer. DSC and XRD were found to be in fairly acceptable and in vitro and ex vivo release profile of microspheres formulation was found to be 80.25 and 76.28% at the end of 6 h. Stability studies for 6 months revealed that the optimized formulation was stable, no changes in physical appearance. Conclusion: Finally, it was concluded that the nasal microspheres of CA may have potential enough for effective drug delivery
目的:研制头孢呋辛酯(CA)鼻黏附微球,作为治疗呼吸道感染的一种替代剂型。材料与方法:以壳聚糖和β -环糊精为缓释聚合物,采用改性乳剂-冻干法制备CA微球。通过24因子设计对模型进行优化,并用方差分析对模型进行验证。评价CA微球的包封效率、体外黏附和药物释放率。对优化后的配方进行了傅里叶红外(FT-IR)分析、粒径、多分散性指数(PDI)和zeta电位、热分析、DSC和XRD、扫描电镜表面形貌以及体外和离体释放动力学研究。主要发现:包封效率为69.21 ~ 80.45%,粒径范围为12.55 ~ 17.22 μm,黏附范围为72.51 ~ 79.68%,药物释放范围为72.21 ~ 83.65%。FT-IR研究确保配方微球中没有药物-聚合物相互作用。测定了微球的PDI和zeta电位,微球的平均粒径和分布都在该范围内,表面形貌显示所有配方均为球形表面和由药物和聚合物组成的外壳包围的圆形腔体。DSC和XRD均可接受,6 h后微球制剂的体外和体外释放谱分别为80.25和76.28%。6个月的稳定性研究表明,优化后的制剂稳定,物理外观无变化。结论:鼻腔CA微球具有足够的给药潜力
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引用次数: 0
A New Validated RP-HPLC Method for the Estimation of Darunavir Ethanolate in Bulk and Tablets 反相高效液相色谱法测定达芦那韦乙醇原药和片剂的含量
IF 0.4 Pub Date : 2020-11-28 DOI: 10.22377/ajp.v14i4.3834
A. Kavitha
Objective: Darunavir ethanolate is the last United States Food and Drug Administration approved protease inhibitor (PI). The drug is used along with other PIs (ritonavir/cobicistat) for the effective management of human immunodeficiency virus (HIV) HIV-1 infection. Darunavir ethanolate exerts its action by binding noncompetitively to HIV protease enzyme. The main objective of the present research work was to develop a new profound and novel reverse-phase high-performance liquid chromatography (RP-HPLC) for the estimation of darunavir ethanolate. Methods: As per the guidelines of the Food and Drug Administration and International Council for harmonization, the method was validated. The HPLC analysis was performed on the waters 2695 equipped with symmetry C18 column 3.5 μm, 150 mm × 4.6 mm, with a mixture of acetonitrile:0.1% phosphate buffer (50:50 V/V) as the mobile phase, at the flow rate of 1 ml/min. The total run time was 5 min and the detection was performed at the wavelength (λ) of 262 nm. Results: The retention time for darunavir ethanolate was found to be 2.269 min. The standard curves were obtained with R2 0.9997 and linear at the concentration range of 8–120 μg/ml. The limit of quantitation and limit of detection for darunavir ethanolate were found to be 0.08 μg/ml and 0.8 μg/ml, respectively. The method’s accuracy was tested by percentage recovery tests and found to be 100.3%. The results obtained were within the accepted standards for linearity, accuracy, precision, specificity, and robustness. Conclusion: The proposed RP-HPLC method can be applied for the routine analytical estimation of darunavir ethanolate in bulk and tablet formulations.
目的:达芦那韦乙醇酸是美国食品药品监督管理局最后批准的蛋白酶抑制剂(PI)。该药物与其他PI(利托那韦/钴司他)一起用于有效管理人类免疫缺陷病毒(HIV)HIV-1感染。达芦那韦乙醇酸盐通过与HIV蛋白酶非竞争性结合发挥作用。本研究工作的主要目的是开发一种新的高效液相色谱法(RP-HPLC)来测定达芦那韦乙醇酸盐。方法:根据美国食品药品监督管理局和国际协调理事会的指导方针,对该方法进行验证。HPLC分析在装有对称C18柱3.5μm,150mm×4.6mm的2695水中进行,流动相为乙腈:0.1%磷酸盐缓冲液(50:50V/V)的混合物,流速为1ml/min。总运行时间为5分钟,检测波长(λ)为262nm。结果:达芦那韦乙醇酸盐的保留时间为2.269分钟。标准曲线的R2为0.9997,在8-120μg/ml的浓度范围内呈线性。达芦那韦乙醇酸的定量限和检测限分别为0.08μg/ml和0.8μg/ml。该方法的准确度通过百分比回收率测试进行了测试,结果为100.3%。获得的结果在线性、准确度、精密度、特异性和稳健性的公认标准范围内。结论:所提出的反相高效液相色谱法可用于原料药和片剂中达芦那韦乙醇酸盐的常规分析。
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引用次数: 0
Geriatric Inguinal Hernia and its Surgical Management – Findings From a Retrospective Study 老年腹股沟疝及其外科治疗——一项回顾性研究结果
IF 0.4 Pub Date : 2020-11-28 DOI: 10.22377/AJP.V14I4.3821
M. S. Iqbal
Objective: The objective of the study was to study the surgical management of inguinal hernia (groin hernia) among geriatric (elderly) patients. Materials and Methods: A retrospective study was conducted from December 2016 to August 2018 in the surgical ward of a university hospital in Malaysia. Geriatric patients operated for surgery during the study period were recruited in the study. A total of 116 cases operated for groin hernia with or without comorbidities and their influence on the overall results of surgical interventions were studied. Results: The mean age of the patients was 71.02 ± 3.1 years, of whom 94 (81%) were male and 22 (19%) were female. In 66 (56.9%) patients, the hernias were simple, while 21 (18.1%) had an obstructive inguinal hernia. In 17 (14.7%) patients, the hernia was incarcerated while 12 cases presented had strangulations. Comorbidities were present in 97 (83.6%) patients. No mortality was found either in elective or in emergency surgery. Conclusion: Comorbidities, type of surgery (elective or emergency), type of hernia (simple or complicated), and age of the patients can make surgery more challenging in the geriatric population.
目的:本研究的目的是研究老年患者腹股沟疝(腹股沟疝)的手术治疗。材料和方法:回顾性研究于2016年12月至2018年8月在马来西亚一所大学医院的外科病房进行。本研究招募了在研究期间进行手术的老年患者。研究了116例有或无合并症的腹股沟疝手术及其对手术干预总体结果的影响。结果:患者平均年龄71.02±3.1岁,其中男性94例(81%),女性22例(19%)。在66名(56.9%)患者中,疝是简单的,而21名(18.1%)患者患有腹股沟梗阻性疝。在17例(14.7%)患者中,疝被嵌顿,而12例出现绞杀。97例(83.6%)患者存在合并症。在择期手术或急诊手术中均未发现死亡病例。结论:合并症、手术类型(选择性或急诊)、疝类型(简单或复杂)和患者年龄会使老年人群的手术更具挑战性。
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引用次数: 1
Comparison and Subjective Evaluation of Safety and Efficacy of Antihypertensive Drugs from the Group Angiotensin-Converting Enzyme and Diuretics 血管紧张素转换酶与利尿剂组降压药物安全性、有效性的比较与主观评价
IF 0.4 Pub Date : 2020-11-28 DOI: 10.22377/ajp.v14i4.3829
Sakhanda Ivanna
Introduction: Cardiovascular diseases are a very significant sociomedical problem in all countries of the world. Proper therapy of cardiovascular diseases, as well as their timely prevention, is one of the most important conditions for increasing life expectancy and maintaining quality of life. One of the most effective ways to achieve this goal is the timely detection and proper treatment of hypertension. Doctors note that in diseases such as stroke, coronary heart disease, including myocardial infarction, and heart and kidney failure, their level may be reduced as a result of adequate antihypertensive therapy. This is especially important for Ukraine, where the incidence of cardiovascular disease is increasing every year. Recently, along with the expansion of opportunities in the treatment of hypertension, there is enough information about the effectiveness of drugs that lower blood pressure. Materials and Methods: Methods such as questionnaires of patients (content analysis of case histories) were used. Data processing was performed using statistical and mathematical methods and graphical analysis. Results: There were some patterns of lowering blood pressure in patients on the background of monotherapy of hypertension and patients following the doctor’s instructions for treatment. Discussion and Conclusion: As a result of the study, it was found that most patients follow the recommendations of doctors on the appointment of antihypertensive drugs.
引言:心血管疾病在世界各国都是一个非常重要的社会医学问题。心血管疾病的适当治疗及其及时预防是提高预期寿命和保持生活质量的最重要条件之一。实现这一目标的最有效方法之一是及时发现和适当治疗高血压。医生们注意到,在中风、冠心病(包括心肌梗死)以及心肾衰竭等疾病中,适当的降压治疗可能会降低其水平。这对乌克兰来说尤其重要,因为乌克兰的心血管疾病发病率每年都在增加。最近,随着高血压治疗机会的扩大,有足够的信息表明降压药物的有效性。材料与方法:采用患者问卷调查(病历内容分析)等方法。使用统计和数学方法以及图形分析进行数据处理。结果:在高血压单药治疗的背景下,患者和遵循医生指导治疗的患者存在一些降压模式。讨论与结论:研究结果发现,大多数患者在服用降压药时遵循了医生的建议。
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引用次数: 0
Formulation, Optimization, and In vivo Evaluation of Clozapine Loaded Transdermal Drug Delivery System for the Treatment of Schizophrenia 氯氮平经皮给药系统治疗精神分裂症的处方、优化和体内评价
IF 0.4 Pub Date : 2020-11-28 DOI: 10.22377/ajp.v14i4.3823
Mayur M. Patel
Introduction: The present research work was intended to develop and optimize transdermal matrix patch of clozapine using Box–Behnken experimental design (Box–Behnken design [BBD]) for improved bioavailability as compared to oral formulation. The 3-factor, 3-level BBD was employed to investigate the combined influence of formulation variables on flux, tensile strength (TS), and in vitro drug release. The generated polynomial equation was validated and desirability function was utilized for optimization. Materials and Methods: Optimized formulation evaluated for physicochemical characterization, Fourier transform infrared, differential scanning calorimetry, in vitro drug release, permeability enhancement potential by ex vivo, skin irritation, and in vivo pharmacokinetics and stability studies. Results: The results of the optimized formulation (F15) showed TS of 6.84 ± 0.64 MPa, flux of 104.80 ± 1.39 (μg/h/cm2), and % drug release after 20 h (Q20) of 82.19 ± 1.12% which was stable up to 6 months in accelerated condition. Observed and the predicted values of the responses were found to be in good agreement. Optimized transdermal patch of clozapine found free from skin irritation as per Draize score method. The pharmacokinetic result had shown the bioavailability of clozapine improved about 2.18-fold after transdermal drug delivery when compared with oral marketed formulation. Discussion and Conclusion: The results of the study revealed that the developed transdermal patch of clozapine can be a promising alternative which provides effective management of schizophrenia in terms of improved patient compliance.
前言:本研究旨在采用Box-Behnken实验设计(Box-Behnken design [BBD])开发和优化氯氮平透皮基质贴剂,以提高口服制剂的生物利用度。采用3因素3水平BBD法考察制剂变量对通量、抗拉强度(TS)和体外释药的综合影响。对生成的多项式方程进行了验证,并利用期望函数进行了优化。材料与方法:优化配方,进行理化表征、傅里叶变换红外、差示扫描量热、体外药物释放、体外渗透性增强潜力、皮肤刺激、体内药代动力学和稳定性研究。结果:优化处方(F15)的TS为6.84±0.64 MPa,通量为104.80±1.39 (μg/h/cm2), 20 h后释药% (Q20)为82.19±1.12%,加速条件下可稳定至6个月。结果表明,观测值与预测值吻合较好。经优化后的氯氮平透皮贴片按Draize评分法无皮肤刺激。药代动力学结果表明,经皮给药后氯氮平的生物利用度比口服上市制剂提高了2.18倍。讨论与结论:本研究结果显示,氯氮平透皮贴剂是一种有希望的替代方法,可以有效地治疗精神分裂症,提高患者的依从性。
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引用次数: 3
The Impact of Diabetes Mellitus on Patients’ Quality of Life 糖尿病对患者生活质量的影响
IF 0.4 Pub Date : 2020-11-28 DOI: 10.22377/ajp.v14i4.3831
M. Iqbal
Objective: This study aimed to measure the impact of diabetes mellitus (DM) on patients’ quality of life (QoL). Materials and Methods: This cross-sectional study involved DM patients that underwent follow-up at a hospital in central Malaysia. Data were collected using self-developed and self-administered questionnaire. Statistical analysis was performed using Statistical Package for the Social Sciences version 24. Results: Around 75 (56.8%) of the patients were satisfied with their daily routine life activities. A total of 88 (66.7%) were also satisfied with their family and friends’ relationships. On the contrary, 109 (82.6%) were not satisfied with their sexual life. There was a statistically significant correlation observed between age and QoL. Conclusion: This study showed that the majority of DM patients had moderate QoL. Diet, living conditions, and concerns about the future had also a greater influence on their overall QoL.
目的:探讨糖尿病(DM)对患者生活质量(QoL)的影响。材料和方法:这项横断面研究涉及在马来西亚中部一家医院接受随访的糖尿病患者。采用自行编制和自行管理的问卷进行数据收集。统计分析使用统计软件包的社会科学版本24进行。结果:75例(56.8%)患者对日常生活活动满意。共有88人(66.7%)对家人和朋友的关系感到满意。相反,对性生活不满意的有109人(82.6%)。年龄与生活质量有统计学意义的相关。结论:本研究显示大多数糖尿病患者的生活质量为中等。饮食、生活条件和对未来的担忧也对他们的总体生活质量产生了更大的影响。
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引用次数: 0
Pharmacists’ Awareness and Perceptions of Biosimilars in Saudi Arabia 沙特阿拉伯药剂师对生物仿制药的认识和认知
IF 0.4 Pub Date : 2020-09-18 DOI: 10.22377/AJP.V14I03.3757
M. Iqbal
Objective: The current study aimed to evaluate practicing pharmacists’ awareness and perceptions about biosimilars in Saudi Arabia. Materials and Methods: A cross-sectional study was performed using a prevalidated and self-administered research tool by convenience sampling method. Registered pharmacists were approached to participate in the study. Descriptive and inferential statistics were performed using the Statistical Package for the Social Sciences version 24.0. P 60%) had good awareness and positive perception toward biosimilars. Conclusion: This study concluded an appropriate awareness and positive perception toward biosimilars among pharmacists in Saudi Arabia. Statistically non-significant association regarding biosimilars’ perception and awareness was observed between male and female pharmacists.
目的:本研究旨在评估沙特阿拉伯执业药剂师对生物仿制药的认识和认知。材料和方法:采用方便抽样法,使用预先验证和自行管理的研究工具进行横断面研究。注册药剂师被邀请参与这项研究。使用社会科学版24.0版的统计软件包进行描述性和推断性统计。P 60%)对生物仿制药有良好的认识和积极的认知。结论:本研究得出结论,沙特阿拉伯药剂师对生物仿制药有适当的认识和积极的看法。在男性和女性药剂师之间,观察到生物仿制药的感知和意识在统计学上没有显著关联。
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引用次数: 2
期刊
Asian Journal of Pharmaceutics
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