Biowaiver studies of newly optimized meloxicam tablets

In this research work biowaiver studies of newly developed and optimized Meloxicam 7.5mg and 15mg water dispersible formulations were carried out at different dissolution media i.e. 0.1N HCl, phosphate buffer pH 4.5, pH 6.8, and pH 7.5 at 50 rpm. For this purpose reference [MA[9] and MB[9] and tests MA[2], MA[4], MA[6], MA[7] and MA[8] [15 mg] and MB[2], MB[4], MB[6], MB[7]and MB8 [7.5 mg] formulations were compared. In vitro patterns were analyzed by using model-independent and model-dependent methods. Results indicated that all formulation at pH 0.1N HCl and phosphate buffer pH 4.5 followed Weibull model, while at pH 6.8 and pH 7.5 all formulations followed Hixson-Crowell model. Similarly results of model independent methods demonstrated that all the reference formulations were found to be similar with the tests formulations. Results indicated that Biowaiver could be granted to all the optimized water dispersible meloxicam formulations of both batches, so waiver for bioequivalence study can be allowed

Development and optimization of intermediate release ketoprofen tablets by central composite design

In this study cost effective direct compression technique was used for the development and optimization of intermediate release [IntR] ketoprofen tablets using central composite design [CCRD]. Fifteen different formulations [F1-F15] were developed using [X[1]] microcrystalline cellulose [Avicel PH-102] [18-51%], [X[2]] methocel K4M [0.1- 25%] and [X[3]] starch [1.5-18%] as selected variables while responses were % friability and Carr's Index [compressibility index]. Powder blends of all formulations were evaluated using Angle of Repose, Carr's Index and porosity. Results of powder blends comply with USP standards and are classified as Fair Excellent. From F1-F15 only four formulations i.e. F6, F7, F14 and F15 were selected on acceptable weight basis, micromeritic properties and on the concentration of excipients. For the assessment of physico chemical properties of the optimized formulations different tests were performed. All results were found to be adequate range. In vitro assessment of the optimized formulations were also carried out in different dissolution media i.e. pH 1.2, phosphate buffer 4.5, pH 6.8 and pH 7.5. Release behaviour of F6, F7, F14 and F15 were estimated by using one - way ANOVA, model - independent, model dependent methods. Results of f1 and f2 showed that all the test formulations i.e. F6, F7, F14 were found to be similar with the reference formulation i.e. F15 at various dissolution media. Also all the formulations followed Hixson-Crowell kinetic model. The parameter n showed Anomalous transport [non - fickian diffusion]. The mean dissolution time [MDT] was found to be in the range of 2.632-2.922. Results of ANOVA indicated no significant difference within and between formulations at different dissolution media as p values were found to be >0.05. Also all the selected formulations were found to be stable at accelerated conditions

Assessment of killing kinetics assay and bactericidal mechanism of crude methanolic bark extract of Casuarina equisetifolia

Casuarina equisetifolia L. is an important medicinal plant widely used to treat various diseases particularly ulcers, diabetes, cough, diarrhea and many infectious and skin diseases. The aim of this research study was to examine the killing mechanism and killing kinetics assay of methanolic bark extract of C. equisetifolia against some highly resistant human pathogens. The comparison on antibacterial activity of extract was firstly done with six different well reputed antibiotics using disk diffusion method. The broth dilution method was used to measure the MIC and MBC values. The mechanism of killing was identified by scanning electron microscopy [SEM] technique. Results showed that higher inhibitory zones were produced by methanolic plant extract than that of some tested antibiotics. The lower MIC and MBC values indicated the antibacterial potency of plant extract. The extract of C. equisetifolia produced a more drop in optical density of S. aureus, MRSA B. subtilis and S. epidermidis up to 12 hrs. The complete destruction of the cell membrane of MRSA was observed after 12 h treatment with plant extract. It is concluded that crude bark extract of C. equisetifolia is potent antimicrobial agent and produced both bacteriostatic and bactericidal effects. Its killing time was extremely faster especially against MRSA. The cell membrane rapturing is a suggested killing mechanism of plant extract

Dexibuprofen: Statistical assessment of drug release kinetics and investigative quality perspective

Healthcare professionals including physicians and pharmacists have been trying since long to come across and work out regarding the issue of generic alternatives, which is highly affected by factors like therapeutic efficacy, cost effectiveness, aesthetic and elegant appearance and implementation of packaging number over the drug product. However, the community pharmacist professionals are also facing difficulty in making decision regarding selection and dispensing the most efficacious brand to the patients. In this regard, the initiation of recent approaches for the development of amenable drug products has led to evolve the concept of generating new avenues for achieving higher patient compliance. Hence, the objective of this study was to evaluate the quality attributes and make comparisons regarding different brands of Dexibuprofen available in market of Karachi, Pakistan. The study is based on evaluation of physical chemical parameters of five different brands. Moreover, a comparative dissolution profile of selected brands of Dexibuprofen was also performed by applying numerous approaches. DEX-1was selected as reference while DEX-2-DEX-5was selected as test brands. Results of all the selected brands met all the compendial requirements. Interpretation of the entire aforementioned test was evaluated using model independent, model- dependent and one - way ANOVA. The work presented in this study has been designed to provide quality standard products easily accessible in Pakistani market

Formulation design, characterization and optimization of cinitapride [1mg] immediate release tablets using direct compression technology

Cinitapride hydrogen tartarate is relatively a new prokinetic agent that widely prescribed for GERD and epigastric pain. Present study was aimed to develop and optimize cinitapride [1 mg] immediate release [IR] tablet formulation[s] by direct compression using central composite rotatable technique. Overall nine formulations [FC1-FC9] were generated by varying the composition of binder avicel PH 102 [X1] and superdisintegrant crospovidone [X2]. The effect of interaction of excipients on hardness [Y1], friability [Y2], disintegration [Y3] and dissolution at 15 min [Y4] were analyzed by RSM plotting. On the basis of physico-chemical evaluation FC3, FC4 and FC6 were found to be the optimized formulations however; FC3 was selected to be the best trial owing to excellent drug release [100.17%] with least friability [0.14%]. These IR tablets showed the release pattern similar to the Weibull model with r2 value of 0.9780.998. The dissimilarity [f1] and similarity indexes [f2] of FC3, FC4, FC6 with the marketed product were estimated to be 2.57 and 76.51, 4.51 and 64.46, 4.32 and 66.78 respectively. Trial optimized formulations were highly stable with the shelf lives of 58-64 months. So, keeping in view the results of present investigation, it is concluded that the technique of manufacturing and optimization is found to be excellent for developing immediate release cinitapride tablets

Assessment of predictor variables and clinical consequences associated with surgical site infection in tertiary care setting, Karachi, Pakistan

Among the well-known Health care-associated infections [HAIs], surgical site infections [SSIs] contribute to considerable high mortality and morbidity rate, substantial prolongation in hospitalization period and extra expenses in terms of treatment cost. This study was aimed to evaluate the predictive variables associated with surgical site infections, and their clinical consequences. This was a prospective, cross sectional study conducted in the surgical department of tertiary care setting in Karachi, Pakistan. Each patient was followed up from the time of admission until time of the discharge postoperatively for 30 days. A total of 554 surgical procedures were performed and 81 SSIs were identified. The predictor variable/risk factors significantly associated with the presence of SSI were age, gender, BMI, ASA score, co-morbid condition, surgical wound class, emergency surgeries, duration of surgery, type of anesthesia, prosthetic implant, pre operative length of stay and pre operative blood transfusion. Outcomes of such studies may be utilized in the design of a multi factorial practice to get better patient's safety and clinical outcomes

Spectrophotometric method development and validation for determination of chlorpheniramine maleate in bulk and controlled release tablets

Spectrophotometric technique is considered to be the simplest and operator friendly among other available analytical methods for pharmaceutical analysis. The objective of the study was to develop a precise, accurate and rapid UV-spectrophotometric method for the estimation of chlorpheniramine maleate [CPM] in pure and solid pharmaceutical formulation. Drug absorption was measured in various solvent systems including 0.1N HCl [pH 1.2], acetate buffer [pH 4.5], phosphate buffer [pH 6.8] and distil water [pH 7.0]. Method validation was performed as per official guidelines of ICH, 2005. High drug absorption was observed in 0.1N HCl medium with lambdamax of 261nm. The drug showed the good linearity from 20 to 60microg/mL solution concentration with the correlation coefficient linear regression equation Y= 0.1853 X + 0.1098 presenting R2 value of 0.9998. The method accuracy was evaluated by the percent drug recovery, presents more than 99% drug recovery at three different levels assessed. The % RSD value

Effects of superdisintegrants in oral dissolving formulation of cinitapride tablets

The initiation of newer techniques and development of mouth dissolving [MD] products has created new avenues of higher patients' compliance. MD formulations are actually lessen the difficulties associated with solid swallowing with better bioavailability of especially poorly soluble drugs. In the current study mouth dissolving tablet [MDT] formulations of cinitapride [1 mg] were prepared by direct compression method using various proportion and combination of superdisintegrants. Nine formulations in three batches were compressed by incorporating low [2%], intermediate [6%] and higher [10%] levels of crospovidone, croscarmellose sodium, sodium starch glycolate. Micromeritic assessment of the powder blends were carried out and were found within the acceptable official limits. All newly developed trial formulations were exposed to different pharmacopoeial and non-pharmacopoeial testing. It was found that FC2 trial tablets containing polyplasdone XL [crospovidone] at level of 6% [4.5 mg] presented the best physico-chemical attributes deemed to be desirable for the ODT products. Disintegration and wetting time of optimized FC2 was computed between 15-17 and 12-15 seconds respectively. The assay and content uniformity of FC2 were estimated to be 100.02+/-0.36 and 99.66+/-1.70 percent correspondingly. On the basis of the findings it was concluded that MDT could be successfully developed by incorporating appropriate concentration of superdisintegrant and their combinations

Incidence of drug interactions in intensive care units in tertiary care settings: Classification, facts and measures

Drug-drug interactions [DDIs] are extremely significant concern, particularly in sensitive population including pediatric and geriatric. Propensity for the development of DDIs is high in patients admitted at intensive care units [ICU]. This study was conducted to evaluate the DDIs incidence, facts and measures in ICU. From a total of 150 cases studied for ICU patients, with the mean age of 56.37+/-12.45 years, 55.33% were male and the rest were female 44.66%. The demographic information like age, gender and main diagnosis details of study participants that were extracted from the patients' clinical record. A statistically significant association between the drug interaction and the number of drugs prescribed per prescription was observed [p <0.0001]. Concerning the onset of outcome, 52% of DDIs distinguished as delayed onset of effect [past 24 hours] and 35% were categorized as rapid onset [within 24 hours]. Despite the facts regarding patient safety and minimizing DIs error, polypharmacy is still frequent in critically ill patients admitted in ICU attributed high risk of adverse reactions due to use of multiple interventions to treat severity of disease condition. Such studies may be used to develop an effective tool for the diagnosis and management of DDIs

Drug utilization and prescribing pattern of antibiotics in a tertiary care setups; trends and practices

Irrational, over and misuse of antibiotics arise as global concern in both hospital and community settings and lead to adverse events including antimicrobial resistance, associated health problems, amplified hospitalization stay and cost. Hence, Drug Utilization Evaluation [DUE] studies are designed to evaluate and improve the prescribing, administration and the rational use of medications. The present study was designed to assess the pattern of antimicrobial drug utilization in in-patients cohort of tertiary care setup in Karachi, Pakistan. This cross sectional observational study was conducted in retrospective manner. World health organization [WHO] guidelines and criteria are considered to evaluate the appropriateness of drug use in various disease conditions. ATC/DDD system was applied to determine the study outcome. High frequency of antibiotics utilization found in respiratory tract infections of both lower [LRTI] 16.8% [n=42] and upper [UTI] 13.2% [n=33]. The estimated total number of drug units administered per month was greater with cefixime [46] and ciprofloxacin [45] both. DDD/100 bed days drug utilization of antibiotics was higher with ciprofloxacin, cefexime and meropenem [47, 46 and 29.25] correspondingly. In conclusion, the current investigation signifies extensive scope for progress in prescribing trend. Drug adherence to customary guidelines of disease management and constraint policies to endorse judicious drug use may be considered vital in healthcare setup

Out of pocket [OOP] cost of treating hypertension in Karachi, Pakistan

Pakistan is categorized to below to middle income countries where two third of the national annual health expenditure is in the form of out of pocket [OOP] cost. A prevalence based study was conducted to determine the OOP cost treatment of hypertension in Karachi by interviewing 350 hypertensive patients aged >30 years through a validated questionnaire. Hypertension [HTN] was classified into stage 1 and stage 2 and was found to be common in females [53.42%] than males [46.57%]. The total costs of stage 1and stage 2 HTN were calculated to be217869.7PKR and17545457.6 PKR respectively. The average treatment cost of stage 1 was observed to be significantly lower [p=0.006] than the cost of stage 2 HTN. Moreover; the cost of antihypertensive drugs, physician fees and laboratory tests were considerably different however; no variation was seen in cost of transport and loss of productivity through absenteeism from work. Overall, the present study indicates that the antihypertensive treatment has imposed a high burden on the pocket of common man and this is a major reason for treatment non-adherence. Consequently, it increases the risks of cardiovascular events, morbidity and mortality. Therefore, effective strategic planning is need of time to reduce OOP cost for better control on hypertension in Pakistan

need of instituting public health education programs in Karachi

Objective: To determine the awareness, need, role, and the effectiveness of the health education programs in improvement of well being of the community/citizens. Study Design: Descriptive cross-sectional study. Place and Duration of Study: The study was conducted, from Aug to Dec 2015 at the four districts of Karachi city

Material and Methods: The instrument of the study was a questionnaire, including basic demographic information of the participants and other 20 items related to need and role of health education programs in control of diseases. A total 250 participants were selected through stratified random sampling design from residential areas of North, South, East and West districts of Karachi. Participants failed to answer item one of the questionnaire were excluded from the study. The data was then analyzed and expressed in percentages and graphs

Results: Total 189 residents were continued the participation belonging to the age group between 18-65 years. Majority of the respondents [96.82%] were in favor of organizing health education activities. About 75.13% believed that such programs have pronounced effect in management of diseases. Furthermore, participants [51.32%] were willing to attend health seminars/symposiums and workshops to be aware to their medical problems. It was also found that they have basic concept of immunization and harmful effects of smoking on health

Conclusion: Over all the residents of Karachi were well aware to the health education and its role in improvement of disease status. Residents showed positive response for participation in health education activities to manage their illness or medical problems. However, the present study involves a smaller population subjects. Authors highly recommended the institution of health education programs in hospitals and community to make the people and environment healthy

Development and validation of stability indicating assay method for cinitapride in bulk and tablets

A simple stability indicating UV-spectrophotometric method has been developed and validated for the determination of cinitapride hydrogen tartrate [CHT] in bulk and solid pharmaceutical dosage form. Drug absorption was measured in different analytical mediums however; maximum absorption was seen in 0.1 N HCl at wavelength [lamda [max]] of 266 nm. The calibration curve was found to be linear over the concentration range from 6 to14 micro g/mL with the correlation coefficient value [r] of 0.999. The LOD and LOQ were estimated to be 0.1019 micro g/ml and 0.309 micro g/ml respectively. The accuracy was evaluated by determining the percent drug recovery, performed at three different levels of 50%, 100% and 150%. The% recovery was found to be in the range of 99.96-100.64%. The precision of the method was determined by inter-day and intra-day variations. The % RSD value <0.5 indicates the underlying method is precise and accurate as well. The developed method was applied to characterize in vitro assay content of few brands of cinitapride [1 mg] available in local market. No interference of the formulation excipients with the drug absorption was observed during assay. Drug substance and drug product were exposed to various stressed conditions [acid, base, oxidative, thermal and photolysis]. Forced degradation testing of drug product showed that the oxidation [20%] was found to be the major degradation pathway of the cinitapride. However; drug estimation was not influenced in presence of degradation moieties formed during acid, base, oxidation, thermal and photolytic breakdown. Overall, the investigated technique is robust and specific that would be successfully used to quantify the cinitapride hydrogen tartarate in pharmaceutical dosage and bulk form in future

Chromatographic method development and validation for the determination of valsartan in biological fluid

A swift, precise and simple HPLC bioanalytical technique with UV detection was established and validated for quantitative estimation of valsartan in human plasma. The analyte was separated from plasma by protein precipitation with acetonitrile and chromatographically separated on Zorbax SB-C18 [5 micro m, 4.6mm x 15cm] column. The solvent mixture system consisting of acetonitrile, water and glacial acetic acid [40:59:1 v/v], was pumped using isocratic mode at 1mL/min flow rate. Samples' detection of drug was made spectrophotometrically at a wavelength of 264nm. The analyte response was instituted to be linear from 0.06 to 8 micro g/mL with a regression value of 0.999. The accuracy of the proposed method was ranged between 97.2-100.3% with 5% RSD. The analytical recovery [>95%] was consistently observed and satisfactory sample stability was also found at different environmental conditions. In conclusion the reported bio-analytical method is easy and robust that was successfully utilized in estimation of valsartan in a pharmacokinetic study

Pharmacokinetic and bioequivalence studies of fast dispersible ketoprofen tablets in healthy volunteers

In the present study the pharmacokinetic and bioequivalence parameter of Ketoprofen 100 mg fast dispersible tablets [test] were measured with marketed [reference] product. This study was accomplished following PDA guidance. A single dose, open labeled, cross over [two way], randomized study design was used to conduct investigation on 12 Pakistani healthy volunteers. At various time points blood samples [l0mL] were drawn i.e. at 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12 and 13hr. Plasma was then separated and ketoprofen concentrations were estimated by validated HPLC technique using LC 20A pump [Shimadzu Corp, Japan] and Spectrophotometric SPD-20Adetector [Shimadzu Corp, Japan]. Ketoprofen concentrations were then analyzed by Kinetica[TM] 4.4.1 [Thermo electron corp, USA] to estimate various compartmental and noncompartmental pharmacokinetic parameters. Various parameters of bioequivalence including AUC,o,, AUCo-oo, AUC/os,, Tmaxcaic and C[maxcaic]w ere compared using ANOVA method [two way]. For log and non-log transformed data the 90 % confidence interval values for AUC [1.0087-1.0704; 1.0099-1.0714], AUC[to], [0.95482-1.0093; 0.95486-1.0098], AUC[last] [0.93373-0.98605; 0.93404-0.98603], C[maxcaic] [0.92978-0.9955; 0.92962-0.99663] and maxcaic [0.89019-0.94116; 0.89095-0.94288] for test and reference products respectively. Results were found to be within the PDA satisfactory range. For the results verification, Schuirman's one sided / test was used. SPSS 17.0 [SPSS Inc] was utilized for the determination of wilcoxon sign rank test. Results showed no carry over effect after first study period. Also test product met the regulatory criteria for bioequivalence with the reference product. Both the formulations were well tolerated

Quality surveillance of immediate release aceclofenac tablets (100 mg) available in local market

Aceclofenac is considered to be an effective drug that has been widely prescribed for multir pjedical complaints globally. Owing to high demand many generic counterpart of aceclofenac tablets are now available in the commercial market. The aim of the present work is to evaluate and compare the quality attributes of various national/local brands of aceclofenac immediate release tablets [l00mg] with the standard multi-national brand available in Pakistan. Physico-chemical evaluation was performed by determining the average tablet weight, thickness

Sensitivity pattern of ceftriaxone against different clinical isolates

Emerging resistance against broad-spectrum antibiotics for standard empiric therapy is a global concern. Ceftriaxone [broad spectrum, third generation cephalosporin] is widely used in tertiary care settings to treat severe bacterial infections usually non-responsive to other antibiotics. The aim of the study is to evaluate the current sensitivity pattern of ceftriaxone [30micro g/disk] among different clinical isolates. For this purpose, three hundred clinical isolates including Escherichia coli [25%], Staphylococcus aureus [30%], Salmonella typhi [17%] and Klebsiella pneumoniae [20%] were collected from different pathological laboratories of Karachi, Pakistan. The in-vitro sensitivity of different Gram positive and Gram-negative bacteria was determined by disk-diffusion technique using 0.5 McFarland standard. Results showed that ceftriaxone was highly sensitive against Escherichia coli [90%] and least sensitive against Klebsiella pneumoniae [65%]. It is concluded that the sensitivity of ceftriaxone is progressively decreasing in comparison with past studies creating an alarming situation. Therefore, continuous surveillance is required to determine the current resistance status of clinical pathogens and for effective anti-microbial therapy

Intermediate release formulations of diclofenac potassium tablets for IVIVC

In recent days response surface methodology [RSM] has widely been applied for development and optimization of cost effective formulations with required quality. Study comprised of three steps including micromeritic comparison of different powder blends of placebo and diclofenac potassium [DP], formulation designing with CCRD [Design Expert, version 7.0.0], and stability testing of selected formulations by using R Gui. Ten formulations [F11-F20] were developed using microcrystalline cellulose [Avicel PH-102] [X1] [13-72%], methocel K15M [X2] [6.59-23.4%] and magnesium stearate [X3] [1.32-4.68%], while responses were % friability and % drug release. Blending rate constant was determined at 3, 6, 9 and 12 minutes. The results of physicochemical parameters were found within acceptable limits. After in vitro testing at pH 1.2, pH 4.5 and pH 6.8, mechanism of drug release, kinetic analysis and statistical evaluation were carried out by model - independent, model-dependent and one-way ANOVA methods. Most formulations followed zero order kinetics at higher pH. Fickian release [0.326

Pharmacokinetic and bioequivalence studies of immediate release diclofenac potassium tablets [50mg] in healthy volunteers

This study was conducted with the aim to determine the pharmacokinetic and bioequivalence of diclofenac potassium 50 mg test [F4] tablet formulation with reference product [Caflam]. Present study was single dose, randomized, two phase cross over design, conducted in 12 healthy Pakistani volunteers and planned in accordance with FDA guidelines. In this study a simple, selective, sensitive and reproducible HPLC procedure was developed and validated for the estimation of diclofenac potassium in plasma. The process was validated in the range of 50 - 0.05 [micro]g.mL-1 and used in bioequivalence trial of two products. Multiple blood samples were collected at various time points [0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 14 hr after treating volunteers with test [F4] and marketed reference brand. Plasma separation and deproteination were carried out with acetonitrile; samples [20[micro]L] were injected using the validated HPLC method. Various pharmacokinetic parameters [compartmental and noncompartmental] were estimated using KineticaTM 4.4.1 [Thermo Electron Corp. USA]. Bioequivalence among the products was established by calculating the 90% CI with log and non log transformed data for C[maxcalc], T[maxcalc], AUC[0-[infinity]], AUC[tot] and AUC[last] using two way ANOVA and Schirmann's Two one sided t- test. No significant difference was found between log and non-log data. The 90% confidence interval values using log transformed data for AUC[0-[infinity]] [0.997-1.024], AUC[tot] [1.004-1.031], AUC[last] [0.997 - 1.024], C[maxcalc] [0.994-1.007] and T[maxcalc] [0.996-1.013] for the trial and reference products were found within the FDA acceptable limits of 0.8-1.25. Results were further verified by the Schirmann's one-sided t test. Results showed the bioequivalence of test and reference formulations. Both the products were well tolerated

Impact of modern learning methods on professional education

Background: The learning methods in health sectors are now facing a great challenge. The study is conducted to determine the effectiveness of new learning methodologies including workshops, seminars and symposiums on the building of students' professional skills

Methodology: A simple questionnaire comprised of closed ended questions was given to four hundred students of different medical universities focusing basic health sciences departments like medical, dentistry and pharmacy

Findings: It was found that medical universities were arranging all above mentioned programs on regular basis and students were used to participate in such engagements. Majority of students [52.4%] were in favor of workshops, they thought workshop as the most beneficial technique to improve their weaknesses. While the likeness to seminars and symposiums were nearly on equal basis. Students were strongly agreed [66.2%] that these ways provide current knowledge of the profession than typical teacher centered lectures

Conclusion: Therefore, it is concluded that all professional universities should organize maximum of such advanced activities to produce students with better professional attitudes