Graduate and postgraduate educational challenges during the COVID-19 pandemic period: its impact and innovations-a scoping review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has transformed the global view of education, including graduate and postgraduate education making the development of an alternative approach in times of social isolation an academic imperative. The present review aims to investigate the challenges experienced among undergraduate and postgraduate education and the strategies adopted to address these challenges during the pandemic. METHOD: The preferred reporting items for the systematic review and meta-analyses extension for Scoping Reviews (PRISMA-ScR) were followed. The aim was to include journal articles published in the English language that discussed the influence of the pandemic on educational processes and applied innovative approaches as a solution to educational challenges. From January to August 2020, PubMed, EMBASE, and Google Scholar were searched for articles, yielding 10,019 articles. Two groups of authors examined the retrieved articles separately to avoid any risk of bias. The title and abstract of the articles were used for scrutiny, followed by full-text screening based on the established inclusion and exclusion criteria. The facts and findings of the studies were also discussed based on per capita income, literacy rate, and Internet accessibility. RESULTS: Thirty of the obtained articles were included in the study. The selected articles were from North and South/Latin America, Asia & Pacific, South Africa, and Europe regions. Nineteen of the selected articles dealt with undergraduate education, ten with postgraduate, and one with both groups. The affordability of digital devices and the availability of Internet services were the major challenges for low- and middle-income economies. The ZOOM platform has been adopted by more than 90% of the education systems. CONCLUSION: Means of communication, including visual media, digitized content, and other web-based platforms, have been recognized as efficient learning and training tools, but have not been fully accessible for mass application and use due to the lack of availability of resources, their cost, and insufficient training among the users. In light of this review, it is suggested that harmonized and collaborative efforts should be made to develop cost-effective and user-friendly tools to overcome the current challenges and prevent future educational crises. SYSTEMIC REVIEW REGISTRATION: The review was not registered.

Formulation development, in vivo bioequivalence and pediatric PBPK modeling studies of taste-masked ciprofloxacin chewable tablets.

A taste-masked chewable tablet of ciprofloxacin using ion exchange resin Kyron T-134 for enhancing compliance for the paediatric population was developed. The drug-to-resin ratio was optimized for maximum taste masking by studying the effects of soaking time (X1) and mixing time (X2) on complexation (%) using Central Composite Rotatable Design (CCRD). The resin complexes were characterized by bitterness score, DSC, FTIR, and PXRD. The complex was further formulated and optimized into chewable tablets through full factorial design, The optimized formulation was subjected to a bioequivalence study, and a virtual approach of PBPK modelling was adapted to predict the pharmacokinetics of the drug in the paediatric group. The drug resin ratio of 1:1.5 yielded an optimum drug loading of 99.05%. The optimized formulation shows minimum disintegration time with more than 99% drug release within 30 min. The formulation F-9 was found to be bioequivalent with a geometric mean ratio of Cmax, Tmax, AUC0-t, and AUC0-∞ within 90% CI. It was concluded that quality by design approach can successfully be applied to optimize the drug resin ratio and PBPK modeling is a successful predictive tool for estimating the pharmacokinetics of ciprofloxacin HCl in the paediatric population.

Halloysite nanotubes-cellulose ether based biocomposite matrix, a potential sustained release system for BCS class I drug verapamil hydrochloride: Compression characterization, in-vitro release kinetics, and in-vivo mechanistic physiologically based pharmacokinetic modeling studies.

This study investigated the ability of natural nanotubular clay mineral (Halloysite) and cellulose ether based biocomposite matrix as a controlled release agent for Verapamil HCl (BCS Class-I). Drug-loaded halloysite was prepared and tablet formulations were designed by varying amount of hydroxy propyl methyl cellulose (HPMC K4M). Physical characterization was carried out using SEM, FTIR, and DSC. Tabletability profiles were evaluated using USP1062 guidelines. Drug release kinetics were studied, and physiologically based pharmacokinetic (PBPK) modeling was performed. Compressed tablets possess satisfactory yield pressure of 625 MPa with adequate hardness and disintegration within 30 min. The initial release of the drug was due to surface drug on tablets, while the prolonged release at later time points (around 80 % drug release at 12 h) were due to halloysite loading. The FTIR spectra exhibited electrostatic attraction between the positively charged drug and the negatively charged Si-O-Si functional group of halloysite, while the thermogram showed Verapamil HCl melting point at ~146 °C with enthalpy change of -126.82 J/g. PBPK modeling exhibited PK parameters of optimized matrix formulation (VER-HNT3%) comparable to in vivo data. The study effectively demonstrated the potential of prepared biocomposite matrix as a commercially viable oral release modifying agent for highly soluble drugs.

SeDeM expert system with I-optimal mixture design for oral multiparticulate drug delivery: An encapsulated floating minitablets of loxoprofen Na and its in silico physiologically based pharmacokinetic modeling.

Introduction: A SeDeM expert tool-driven I-optimal mixture design has been used to develop a directly compressible multiparticulate based extended release minitablets for gastro-retentive drug delivery systems using loxoprofen sodium as a model drug. Methods: Powder blends were subjected to stress drug-excipient compatibility studies using FTIR, thermogravimetric analysis, and DSC. SeDeM diagram expert tool was utilized to assess the suitability of the drug and excipients for direct compression. The formulations were designed using an I-optimal mixture design with proportions of methocel K100M, ethocel 10P and NaHCO3 as variables. Powder was compressed into minitablets and encapsulated. After physicochemical evaluation lag-time, floating time, and drug release were studied. Heckel analysis for yield pressure and accelerated stability studies were performed as per ICH guidelines. The in silico PBPK Advanced Compartmental and Transit model of GastroPlus™ was used for predicting in vivo pharmacokinetic parameters. Results: Drug release follows first-order kinetics with fickian diffusion as the main mechanism for most of the formulations; however, a few formulations followed anomalous transport as the mechanism of drug release. The in-silico-based pharmacokinetic revealed relative bioavailability of 97.0%. Discussion: SeDeM expert system effectively used in QbD based development of encapsulated multiparticulates for once daily administration of loxoprofen sodium having predictable in-vivo bioavailability.

SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™.

The study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full factorial osmotic drug delivery was applied. A 24 Full-factorial design was used to make the trial formulations of tramadol HCl osmotic tablets using NaCl as osmogen, Methocel K4M as rate controlling polymer, and avicel pH 101 as diluent. The preformulation characteristics of formulations (F1-F16) were determined by applying SeDeM Expert Tool. The formulation was optimized followed by in-vivo predictive pharmacokinetic assessment using PBPK "ACAT" model of GastroPlus™. The FTIR results showed no interaction among the ingredients. The index of good compressibility (ICG) values of all trial formulation blends were ≥5, suggesting direct compression is the best-suited method. Formulation F3 and F4 were optimized based on drug release at 2, 10, and 16 h with a zero-order kinetic release (r 2 = 0.992 and 0.994). The SEM images confirmed micropores formation on the surface of the osmotic tablet after complete drug release. F3 and F4 were also stable (shelf life 29.41 and 23.46 months). The in vivo simulation of the pharmacokinetics of the PBPK in-silico model revealed excellent relative bioavailability of F3 and F4 with reference to tramadol HCl 50 mg IR formulations. The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies.

Nanoclay-Based Composite Films for Transdermal Drug Delivery: Development, Characterization, and in silico Modeling and Simulation.

Purpose: Halloysite nanotubes (HNTs) are a versatile and highly investigated clay mineral due to their natural availability, low cost, strong mechanical strength, biocompatibility, and binding properties. The present work explores its role for retarding and controlling the drug release from the composite polymer matrix material. Methods: For this purpose, nanocomposite films comprising propranolol HCl and different concentrations of HNTs were formulated using the "solution casting method". The menthol in a concentration of 1% w/v was used as a permeation enhancer, and its effect on release and permeation was also determined. Quality characteristics of the nanocomposite were determined, and in vitro release and permeation studies were performed using the Franz diffusion system. The data was analyzed using various mathematical models and permeation parameters. Optimized formulation was also subjected to skin irritation test, FTIR, DSC, and SEM study. Systemic absorption and disposition of propranolol HCl from the nanocomposites were predicted using the GastroPlus TCAT® model. Results: The control in drug release rate was associated with the higher concentration of HNTs. F8 released 50% of propranolol within 8 hours (drug, HNTs ratio, 1:2). The optimized formulation (F6) with drug: HNTs (2:1), exhibited drug release 80% in 4 hours, with maximum flux of 145.812 µg/cm2hr. The optimized formulation was found to be a non-irritant for skin with a shelf life of 35.46 months (28-30 ℃). The in silico model predicted Cmax, Tmax, AUCt , and AUCinf as 32.113 ng/mL, 16.58 h, 942.34 ng/mL×h, and 1102.9 ng/mL×h, respectively. Conclusion: The study demonstrated that HNTs could be effectively used as rate controlling agent in matrix type transdermal formulations.

Modification and validation of liquid chromatographic method for the quantification of ciprofloxacin in human plasma and its application to a bioavailability study.

A new simple, accurate, precise and sensitive liquid chromatographic method for the analysis of Ciprofloxacin in human plasma, suitable for quantification of drug was developed and validated using HPLC-UV method. The analyte was chromatographically separated from endogenous plasma components on a C-18 reversed phase column (5µm, 25cm × 0.46cm) and detected at 278nm. The sample pretreatment was carried out with acetonitrile on 200µl of plasma. The Lower limit of quantification (LLOQ) was 0.04 µg/ml with linearity in the range 0.04-4 µg/ml and coefficient of correlation value (R2)>0.995. The method was successfully validated as per current FDA guidance for necessary parameters and applied to a pilot bioavailability study conducted on six healthy volunteers with marketed Ciprofloxacin 250mg immediate release tablets. The plasma concentrations were subjected to non-compartmental analysis for calculation of pharmacokinetic parameters like Cmax, Tmax, AUCo-t, AUC 0-∞ and t½ etc. The mean values of Cmax and Tmax were found to be 1.35±0.09µg/ml and 1.25±0.27h respectively while for other pharmacokinetic parameters including AUCo-t, AUC0-∞ were found to be 5.98±0.96 µg/ml×h and 6.34±1.07µg/ml×h. The drug exhibited half-life (t½) of 3.94±0.33h. The obtained results proved the suitability of the method for routine pharmacokinetic studies of Ciprofloxacin.

A Journey From SARS-CoV-2 to COVID-19 and Beyond: A Comprehensive Insight of Epidemiology, Diagnosis, Pathogenesis, and Overview of the Progress into Its Therapeutic Management.

The 2019 novel coronavirus (2019-nCoV), commonly known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), was first revealed in late 2019 in Wuhan city, Hubei province, China. It was subsequently spread globally and thereby declared as a pandemic by WHO in March 2020. The disease causes severe acute respiratory illness and is highly contagious due to the fast-onward transmission. As of the mid of November 2020, the disease has affected 220 countries with more than 16 million active cases and 1.3 million deaths worldwide. Males, pregnant women, the elderly, immunosuppressed patients, and those with underlying medical conditions are more vulnerable to the disease than the general healthy population. Unfortunately, no definite treatment is available. Although remdesivir as an antiviral had been approved for use in those above 12 years of age and 40 kg weight group, it has been observed to be ineffective in large-scale SOLIDARITY trials by WHO. Moreover, dexamethasone has been found to increase the recovery rate of ventilated patients; oxygen and inhaled nitric oxide as a vasodilator have been given emergency expanded access. In addition, more than 57 clinical trials are being conducted for the development of the vaccines on various platforms. Two vaccines were found to be significantly promising in phase III results. It is concluded that till the approval of a specific treatment or development of a vaccine against this deadly disease, the preventive measures should be followed strictly to reduce the spread of the disease.

Investigating Halloysite Nanotubes as a Potential Platform for Oral Modified Delivery of Different BCS Class Drugs: Characterization, Optimization, and Evaluation of Drug Release Kinetics.

PURPOSE: This study systematically investigated the potential of four model drugs (verapamil HCl, flurbiprofen, atenolol, and furosemide), each belonging to a different class of Biopharmaceutics Classification Systems (BCS) to be developed into oral modified release dosage forms after loading with halloysite nanotubes (HNTs). METHODS: The drugs were studied for their loading (mass gain %) by varying solvent system, method, pH, and ratios of loading into the nanotubes using D-optimal split-plot design with the help of Design Expert software. Drug-loaded halloysites were characterized by XRD, DTA, FTIR, SEM, and HPLC-UV-based assay procedures. Dissolution studies were also performed in dissolution media with pH 1.2, 4.5, and 6.8. Moreover, the optimized samples were evaluated under stress stability conditions for determining prospects for the development of oral dosage forms. RESULTS: As confirmed with the results of XRD and DTA, the drugs were found to be converted into amorphous form after loading with halloysite (HNTs). The drugs were loaded in the range of ~7-9% for the four drugs, with agitation providing satisfactory and equivalent loading as compared to vacuum plus agitation based reported methods. FTIR results revealed either only weak electrostatic (verapamil HCl and flurbiprofen) or no interaction with the surface structure of the HNTs. The dissolution profiling depicted significantly retarded release of drugs with Fickian diffusion from a polydisperse system as a model that suits well for the development of oral dosage forms. HPLC-UV-based assay indicated that except furosemide (BCS class IV), the other three drugs are quite suitable for development for oral dosage forms. CONCLUSION: The four drugs investigated undergo phase transformation with HNTs. While agitation is an optimum method for loading drugs with various physicochemical attributes into HNTs; solvent system, loading ratios and pH play an important role in the loading efficiency respective to the drug properties. The study supports the capability of developing HNT-based modified release oral dosage forms for drugs with high solubility.

QbD based Eudragit coated Meclizine HCl immediate and extended release multiparticulates: formulation, characterization and pharmacokinetic evaluation using HPLC-Fluorescence detection method.

This study is based on the QbD development of extended-release (ER) extruded-spheronized pellets of Meclizine HCl and its comparative pharmacokinetic evaluation with immediate-release (IR) pellets. HPLC-fluorescence method was developed and validated for plasma drug analysis. IR drug cores were prepared from lactose, MCC, and PVP using water as granulating fluid. Three-level, three-factor CCRD was applied for modeling and optimization to study the influence of Eudragit (RL100-RS100), TEC, and talc on drug release and sphericity of coated pellets. HPLC-fluorescence method was sensitive with LLOQ 1 ng/ml and linearity between 10 and 200 ng/ml with R2 > 0.999. Pharmacokinetic parameters were obtained by non-compartmental analysis and results were statistically compared using logarithmically transformed data, where p > 0.05 was considered as non-significant with a 90% CI limit of 0.8-1.25. The AUC0-t and AUC0-∞ of ER pellets were not significantly different with geometric mean ratio 1.0096 and 1.0093, respectively. The Cmax of IR pellets (98.051 ng/ml) was higher than the ER pellets (84.052 ng/ml) and the Tmax of ER pellets (5.116 h) was higher than the IR pellets (3.029 h). No significant food effect was observed on key pharmacokinetic parameters of ER pellets. Eudragit RL100 (6%) coated Meclizine HCl pellets have a potential therapeutic effect for an extended time period.

Aceclofenac fast dispersible tablet formulations: Effect of different concentration levels of Avicel PH102 on the compactional, mechanical and drug release characteristics.

The objective of this study was based on the formulation development of fast dispersible Aceclofenac tablets (100 mg) and to evaluate the influence of pharmaceutical mixtures of directly compressible Avicel PH102 with Mannitol and Ac-di-sol on the compressional, mechanical characteristics and drug release properties. Fast dispersible Aceclofenac formulations were developed by central composite design (CCD). Among them the best possible formulation was selected on the basis of micromeritic properties, appropriate tablet weight and disintegration time for further study. Tablets were directly compressed using manual hydraulic press with a compressional force ranging from 7.2 to 77.2 MN/m2. Pre and post compression studies were performed and the compressed formulations (FA-FF) were assessed for different quality tests. The Heckel and Kawakita equations were applied for determination of compressional behavior of formulations. The quality attributes suggested that formulation (FB) containing avicel PH 102 (20%), mannitol (25%) and ac-di-sol (3%) as best optimized formulation showing better mechanical strength i.e. hardness 35.40 ± 6.93N, tensile strength 0.963 MN/m2, and friability 0.68%. Furthermore, compressional analysis of FB showed lowest PY value 59.520 MN/m2 and Pk value 1.040 MN/m2 indicating plasticity of the material. Formulation FB disintegrated rapidly within 21 seconds and released 99.92% drug after 45 min in phosphate buffer pH 6.8. Results of drug release kinetics showed that all formulations followed Weibull and First-order models in three different dissolution media. Avicel PH102 based formulation mixture exhibit excellent compactional strength with rapid disintegration and quick drug release.

Comparative pharmacokinetics of osmotic-controlled and immediate-release Eperisone tablet formulation in healthy human subjects using a sensitive plasma LC-ESI-MS/MS method.

To evaluate and compare the pharmacokinetic (PK) characteristics of a newly developed oral osmotically controlled drug delivery system of Eperisone 150 mg tablets with Eperisone immediate release (IR) marketed tablet brand as a reference formulation. It was a single dose, two treatment, two sequence, randomized, crossover study, involving 12 healthy human subjects. A modified, sensitive LC-ESI-MS/MS method was developed and validated as per FDA guidelines for estimation of Eperisone in plasma using a simple extraction and quick protein precipitation method. Non-compartmental pharmacokinetic model was used for PK analysis. Results were statistically compared using logarithmically transformed data, where p > 0.05 was considered as non-significant with 90% CI limit of 0.8-1.25. The bio-analytical method used for estimating drug plasma concentration was found to be simple, selective, linear, accurate and precise with 0.01 ng/ml as limit of detection. The comparative PK analysis revealed an insignificant difference in AUC0-∞, AUC0-t, Vz/F, Cl/F and t1/2λz, whereas a significant difference in Cmax, Tmax and MTTs were found. The relative bioavailability of Eperisone osmotic tablet was 109.7%. The osmotic controlled release drug formulation was found to release Eperisone for an extended period with less inter individual fluctuation in pharmacokinetic variables.

HPLC-UV method for simultaneous quantitation of artemether and lumefantrine in fixed dose combination orodispersible tablet formulation.

This paper describes the development and validation of a high performance liquid chromatography (HPLC-UV) method for the simultaneous quantitative determination of artemether and lumefantrine in fixed dose combination tablets. Chromatographic quantitation was carried out on a C-18 column Mediterrania Sea 18 (250×4.6 mm i.d.; 5 µm particle size) using a mobile phase consisting of 80:20 v/v mixture of acetonitrile and 0.05 % trifluoroacetic acid with final pH adjusted to 2.35 at flow rate of 1 ml/minute. The eluents was detected using photo diode array detector at wavelength of 210nm for artemether and 286 nm for lumefantrine. The retention times were ~5.8 mins for artemether and ~7.3 mins for lumefantrine. The newly developed method was validated and was found linear (r2 >0.99), precise (R.S.D. <2.0%), accurate, specific and robust. The artemether contents in the tablet formulation varied from 99.026 % to 99.347%, while lumefantrine contents were 99.546-99.728 %.

Clay nanotubes as a novel multifunctional excipient for the development of directly compressible diclofenac potassium tablets in a SeDeM driven QbD environment.

Halloysite is a unique biocompatible aluminosilicate clay mineral with powder particles predominantly comprising of concentrically rolled nanotubular aggregates. Some recent studies have also contributed to its prospective case in oral drug delivery and dosage forms albeit with limited commercial viability. In this study, we have investigated the use of halloysite nanotubes (HNTs) as a directly compressible multifunctional tableting excipient using SeDeM diagram expert tool. SeDeM experimentations revealed that ~68% HNTs in the formulations were enough to be used as a directly compressible filler, binder, and disintegrant in diclofenac potassium formulations. In the next phase, a total of 8 formulations blends (IRF1-8) of diclofenac potassium (50 mg) with HNTs and Starch 1500® were prepared in different ratio using simple lattice mixture design and all were found satisfactory for direct compression. Compressed tablets (167 mg) had narrow weight variation (SD = ± 1.78 mg), good hardness (~9-9.5 kg), acceptable friability (<0.7%) and fast disintegration time (<1.5 min). Moreover, the cumulative dissolution at 1 h in phosphate buffer pH 6.8 was found compliant with the compendial criteria (> 92% against 75%). The dissolution profile was best fitted with Peppas-Sahlin model with Fickian diffusion as the only mechanism. f2 similarity test revealed that almost all the tablets were pharmaceutical equivalent to the marketed formulation of the drug. A shelf-life of ~34 months was found upon long-term stability testing of the optimized formulation. This study demonstrates that this novel and economically viable clay material has a strong potential for commercial use in tableting of drug by direct compression.

In-vitro assessment of cytotoxicity of halloysite nanotubes against HepG2, HCT116 and human peripheral blood lymphocytes.

Halloysite is a clay mineral with chemical similarity to kaolin, a pharmaceutical ingredient. It consists of mainly aluminosilicate nanotubular particles in the size range of ∼ 200-1000 nm. Many studies have tried to empirically explore this novel clay for its potential in drug delivery systems but no work has yet studied its cytotoxicity from the perspective of oral drug delivery system. In this study, the halloysite nanotubes (HNTs) were subjected to size distribution analyses, which reveal more than 50% of nanotubes in the size range of 500 nm and rest mainly in the sub micrometer range. HNTs were then evaluated for in-vitro cytotoxicity against HCT116 (colorectal carcinoma) and HepG2 (hepatocellular carcinoma) cells which represent the earliest entry point and the first accumulating organ, respectively, for nanoparticles en-route to systemic circulation after oral delivery. Moreover, HNTs were tested for their cytogenetic toxicity against human peripheral blood lymphocytes. Both these results collectively indicated that HNTs are generally safe at practical concentrations of excipients for oral dosage forms.

Chlamydia trachomatis related knowledge and practices in medical practioners--a survey.

INTRODUCTION: Chlamydia trachomatis is a frequently encountered condition by general physicians, urologists and infectious diseases specialists. It can affect both genders and causes significant morbidity if not treated properly and promptly. In addition, it can cause ophthalmia neonatorum, which manifests as neonatal conjunctivitis in the newborns. METHODOLOGY: The data was collected from fourteen tertiary care hospitals in two provinces of Pakistan during the time period of four months (September-December 2013). Inclusion criteria included all medical practitioners working at those hospitals and there were no limitations of age and gender to participate. The participants were approached through email which included a self administered questionnaire. Written consent was obtained from the participants and the study was approved by the ethical committee of all selected hospital. RESULTS: Overall 130 participants participated with a response rate of 65%. Females were 52.3% and males were 47.7%. In the study 17.7% of male and 29.4% of female participants proclaimed that they referred a patient to an infectious disease specialist in case the diagnosis of Chlamydia was dubious. 72.5% of the male and 55.8% of the female medical practitioners indicated that they yield detailed sexual history from the patients with Chlamydia. Regarding inquiring about the drugs history from the patient at risk of STDs, 22.6% male and 35.3% of female participants informed that they took a detailed drug history. Only 1.5% of the female medical practitioners notified Chlamydia to the partner of diseased patient themselves (provider referral). 24% male and 17.6% female participants had an understanding regarding the definite test of diagnosis for sexually transmitted Chlamydia. CONCLUSION: More sexual health skills development is required in medical practitioners working in Pakistan. The major deficient areas are sexual and drug history taking, management of sexually transmitted diseases and partner notification.

Simultaneous quantitation of aspirin, amlodipine and simvastatin in a fixed dose combination of encapsulated tablet formulation by HPLC-UV method.

A high-pressure liquid chromatography (HPLC-UV) based simple and specific method for simultaneous quantitative determination of aspirin, amlodipine besylate and simvastatin in a capsule formulation has been developed and validated according to ICH guidelines. Chromatographic separation of the three drugs was carried out by aSpherisorbODS2 reverse phase column (4.6 x 250 mm; 5 µm) using amobile phase, which consisted of 70: 30 (v/v) mixture of acetonitrile and triethylamine phosphate buffer (pH 3; 0.015 M) with final pH adjusted to 2.5 using dilute ortho-phosphoric acid, at a flow rate of 1mL/min. The eluents were detected at UV wavelength of 237 nm and the retention times for aspirin, amlodipine besylate and simvastatin were ~2.7 mins, ~6.1 mins and ~10.5mins, respectively. This method is suitable and specific for the three drugs and was found to be linear (R2>0.995), accurate, specific, reproducible and robust in the concentration range of 375 to 1125mcg/ml for aspirin, 25 to 75mcg/ml for amlodipine besylate and 50 to 150mcg/ml for simvastatin. This simple and convenient method could be easily utilized for the characterization and quantitation of the three drugs in a single formulation for combination therapy of cardiovascular diseases.

Hepatocyte cytotoxicity evaluation with zinc oxide nanoparticles.

Our innate immunity is composed of several integral leukocytes including neutrophil, NK cell, macrophage or so. They are usually known to produce reactive oxygen species (ROS), in order to induce cell damages by these oxidizing reagents, and finally disrupting mitochondrial membrane to release cytochrome c. It is quite interesting to cancer therapy that the overexpressed cytochrome c level by ROS can lead to cancer cell death. Activated neutrophils exert anti-tumor effects against several carcinomas such as human skin melanoma by the increased production of ROS. To mimic the natural killing system, several nanoparticulates which contain cytotoxic properties have been in demand. Representatively, zinc oxide (ZnO) nanoparticles have been reported to have anti-bacterial and anti-cancer activity against various cancer cell lines due to production of ROS. They are shown to have preferential anti-cancer activity possibly due to higher level of oxidants and ROS in cancer cells. Inspired by these studies, we carried out the cytotoxicity evaluation of ZnO nanoparticulates against hepatocellular carcinoma. Our investigations were conducted by (1) screening the best size of ZnO (among 5, 50, and 100 nm) and the optimized time for anti-cancer effect against HepG2 cell line, (2) determining the apoptosis in the cells, and (3) regulating the production of intracellular ROS by ZnO nanoparticles. The ZnO nanoparticles revealed the dose-dependent toxic effect on HepG2 cells, irrespective of the sizes.

Patients' opinion of pharmacists and their roles in health care system in Pakistan.

BACKGROUND: Pharmacist-patient association is a decisive component in improving health care system. To offer patient centred services, the pharmacists need to fully understand patients' perspectives and views to meet their needs and expectations. PURPOSE: To evaluate patients' perception of pharmacist and pharmacy practice in Pakistan. METHODS: A cross sectional study was conducted between July and September 2012 on patients attended out-patient clinic in a teaching hospital of Pakistan. By using raosoft sample size calculator, questionnaires were distributed to a sample of 376 patients. Questionnaire included different section which evaluated the demographic information, frequency and reason of interaction, perception and choice of pharmacy. Statistical analysis was done by using SPSS (v.17). RESULTS: A total of 301, out of 376, surveys returned giving a response rate of 80%. 51.8% (n = 156) participants interacted with pharmacist on regular basis. The major reasons of interaction were drug alternative and drug availability queries (41.5%, n = 125 and 26.2%, n = 79). The finding also showed that 84.1% (n = 253) of participants agreed that pharmacists are important part of health care system. Interestingly, all the patients (n = 301) either agreed or strongly agreed that discount was the major influencing factor on their choice of pharmacy. CONCLUSION: The patients' perception of pharmacist in Pakistan was generally positive but their understanding is very primitive as majority of the patients are unaware of pharmaceutical care services. However, they are more devoted to witness such services being practiced in Pakistan. This transition in practice could be brought into certainty by proactive involvement of pharmacists in community setup.