In Vitro In Vivo Extrapolation and Bioequivalence Prediction for Immediate-Release Capsules of Cefadroxil Based on a Physiologically-Based Pharmacokinetic ACAT Model.

Physiologically based pharmacokinetic (PBPK) modeling is a mechanistic concept, which helps to judge the effects of biopharmceutical properties of drug product such as in vitro dissolution on its pharmacokinetic and in vivo performance. With the application of virtual bioequivalence (VBE) study, the drug product development using model-based approach can help in evaluating the possibility of extending BCS-based biowaiver. Therefore, the current study was intended to develop PBPK model as well as in vitro in vivo extrapolation (IVIVE) for BCS class III drug i.e. cefadroxil. A PBPK model was created in GastroPlus™ 9.8.3 utilizing clinical data of immediate-release cefadroxil formulations. By the examination of simulated and observed plasma drug concentration profiles, the predictability of the proposed model was assessed for the prediction errors. Furthermore, mechanistic deconvolution was used to create IVIVE, and the plasma drug concentration profiles and pharmacokinetic parameters were predicted for different virtual formulations with variable cefadroxil in vitro release. Virtual bioequivalence study was also executed to assess the bioequivalence of the generic verses the reference drug product (Duricef®). The developed PBPK model satisfactorily predicted Cmax and AUC0-t after cefadroxil single and multiple oral dose administrations, with all individual prediction errors within the limits except in a few cases. Second order polynomial correlation function obtained accurately predict in vivo drug release and plasma concentration profile of cefadroxil test and reference (Duricef®) formulation. The VBE study also proved test formulation bioequivalent to reference formulation and the statistical analysis on pharmacokinetic parameters reported 90% confidence interval for Cmax and AUC0-t in the FDA acceptable limits. The analysis found that a validated and verified PBPK model with a mechanistic background is as a suitable approach to accelerate generic drug development.

Adaptation of Research Project Requirement at Pharmacy Undergraduate Studies: Students' Perception, Attitude, and Experiences.

Objective: To determine the final year pharmacy undergraduate students' attitudes toward research after completing a research project. Methods: A research project was introduced in the final year of the PharmD program in January 2022. After a period of one year, in Janurary 2023, students submitted their final research to the faculty members. The survey was conducted from 1st March to 30st April 2023 using a study tool that contained items asking students' demographic, their research perceptions, attitude and experience, and also motivation/barriers faced during the research project. Descriptive and t-test statistics were utilized to compare the means of subgroups at a level of significance, i.e., p < 0.05. The data were also analyzed using Goodman and Kruskal's gamma and Mann-Whitney U test. Results: Majority of the students (93.8%) agreed regarding the significance of research in the pharmacy profession. Students were found to have their projects a worthwhile learning opportunity (94.2%). Students' motivation to execute research project stems from mandatory curriculum courses, improving clinical or hospital pharmacist training and fulfilling research skills (90%). Barriers hindered include lack of training, time, and patient follow-up (approximately 70%). Conclusion: The current study's finding was concluded with the fact that research is a valuable component of a well-rounded education and can enhance a pharmacist's skills. However, they need a combination of formal education and practical experience to pursue a profession in pharmacy.

Validation of questionnaire regarding online teaching (QOT) during Covid-19 in Karachi, Pakistan.

The present study involved an extra-cultural adaptation and validation of questionnaire regarding online teaching (QOT) to know faculty perception, attitude and experiences of online teaching. Cronbach's alpha was determined for assessing internal reliability of QOT and found to be 0.886, confirmed that the scale have good reliability. Factor Analysis of the scale (Principal Component Analysis) was used to examine factor structure and then trailed by varimax rotation. The items were allocated four sub scales. A survey technique was used for the validation of QOT and the survey was conducted during September-December' 2020 in private and public universities of Karachi to determine the pharmacy faculty's perception and experience regarding online teaching. Approximately 35% responded that "It is very easy to prepare and deliver an online course" and 45% opined that "The universities offering Pharm.D should adopt the use of e-learning for teaching in future to complement traditional teaching". Majority of the faculty were in favor of starting online teaching during pandemic to complete semester on time (72%). However, in-campus courses contribute more to students' learning than online courses in pharmaceutical sciences (65.5%). The present study summarizes that academic staff did opt online teaching over one-to-one teaching in the lock down situation during Covid-19 pandemic however, they agreed not to replace traditional teaching to online teaching. Teachers recognized some difficulties and challenges during online teaching including difficulty in preparing lecture for online teaching than traditional classroom teaching, shortage of long time training sessions. Female teachers were inclined to online teaching than male and lecturers tend to prefer online teaching compared to senior teachers. Universities and administration should take imperative acts for improving online teaching for better learning during lock down or any other situation where social distancing is required.

High performance liquid chromatographic method validation for determination of rosuvastatin calcium in tablet dosage forms.

A precise, sensitive and quick High Performance Liquid Chromatographic (HPLC) method for the determination of rosuvastatin calcium in bulk and tablet dosage forms has been validated. The chromatographic scheme involved: Sil-20A auto sampler, LC-20A pump, SPD-20A UV/visible detector with separation attained by C18 column at 40ºC temperature through a mobile phase of acetonitrile and buffer (50:50) at a flow rate of 1.0ml/min. The method is precise (%RSD for intra-day and inter-day extended between 1.06-1.54% and 0.103-1.78%) and linear (r2=0.9997). Limit of detection and quantification (LOD & LOQ) of the adopted method were 0.78 and 1.56µg/ml. The proposed HPLC method was established to be sensitive, precise and swift that can be proficiently adopted in quality control/quality assurance laboratories for predictable investigation of the bulk and oral solid dosage forms of rosuvastatin calcium.

Prescribing pattern of angiotensin receptor blocker: A study of errors and drug-drug interactions.

Prescriptions comprising multi-drug therapy mostly illustrate the prescribing error. The phenomenon of error is bonded with human inaccuracy. The erroneous practice is observed in under developed countries like Pakistan, Bangladesh and also in developed ones. Consequently drug-drug interaction is one of the most common error associated with potentially serious adverse response even death. Accordingly the present study was conducted to assess the prevalence of prescribing errors and drug-drug interactions in out-patients receiving angiotensin receptor blockers. The study was done with population size one hundred fifty prescriptions obtained from different out-patient settings in Karachi. The prescriptions were screened for prescribing errors and risk factors for drug-drug interactions. Drug-drug interactions were recognized by Micromedex.2.0.Drug-Reax®database. The most common type of error was omission error. These errors were patient's age, weight and diagnosis found in 51.3%, 97.3% and 74% of prescriptions, respectively. The prevalence of drug-drug interaction was 38%. A total of 746 drugs were prescribed with an average of 5 drugs per prescription and 450 medication errors were detected. Majority of the interaction were moderate (19.33%), others were minor (14%) and major (6%) in severity. Patients who prescribed many drugs (more than 5 drugs in a while) had a higher risk of developing drug-drug interactions (OR=4.76; 95% CI=2.30-9.64; p=0.0001*).The study data reports the occurrence of prescribing errors in Karachi and also necessitate the need of clinical pharmacist's services in health care system. The step will help to minimize the risk factors by having the drug prescriptions reviewed by the pharmacists.

Perspectives about Pandemic Influenza and Its Prophylactic Measures among Final Year Pharmacy Students in Karachi, Pakistan.

AIMS: In flu pandemics, pharmacy students' knowledge, attitudes, and practices are critical to save patients life. The objective of study was to determine the knowledge of and attitude toward the pandemic influenza among the pharmacy students of Karachi, Pakistan. SETTINGS AND DESIGNS: The cross-sectional study was conducted from September to December 2014 by adopting a prevalidated questionnaire distributed to senior pharmacy students (final year) in seven private and public sector universities of Karachi. MATERIALS AND METHODS: A total of 443 pharmacy students responded the survey. Data regarding sociodemographic characteristics of the students, perceptions, level of knowledge and attitudes toward influenza, and prophylactic measures were collected. STATISTICAL ANALYSIS: To compute the correlation between different variables, data were analyzed using Pearson's Chi-square statistic method. P < 0.05 was considered statistical significance for all analysis. RESULTS: Influenza was identified as a viral disease (n = 423; 95.48%) and 282 (71.2%) students correctly identified it as disease affecting humans and pigs. Textbooks reported as most common source of knowledge (n = 282; 64%). Most common symptoms identified were fever (81.94%), sore throat (64.1%), and nonproductive cough (43.34%). The most common preventive measures were covering nose and mouth (268; 60.5%) and wearing protective coverings (254; 57.3%). Only half of the students correctly reported about the route of administration (180; 40.6%) and strains in vaccine (186; 41.98%). The best time for administration of such vaccine was known by only 156 pharmacy students (35.34%). The majority of the students (82.6%) had no idea about the manifestation of influenza pandemic. Knowledge regarding influenza differed according to gender and institutions differing in their affiliation with tertiary care hospitals. CONCLUSION: It was observed that knowledge about disease progression, transmission, vaccination, and treatment in pharmacy students, especially those who are not getting clinical training in tertiary care hospitals was limited. There is an urgent need to develop awareness programs to increase knowledge of influenza among clinical pharmacists as they are more susceptible to infections and community as a whole.

Utilization and Impact of Electronic and Print Media on the Patients' Health Status: Physicians' Perspectives.

AIMS: Despite an increased popularity of print and electronic media applications, there is a paucity of data reflecting doctors' opinions regarding efficient utilization of these resources for the betterment of public health. Hence, this study aimed to investigate the perception of physicians toward the effect of electronic and print media on the health status of patients. SETTING AND DESIGN: The current research is a cross-sectional study conducted from January 2015 to July 2015. The study population comprised physicians rendering their services in different hospitals of Karachi, Pakistan, selected by the nonprobability convenience sampling technique. In this study, 500 questionnaires were distributed through email or direct correspondence. METHODS AND MATERIALS: Physicians' perception toward the impact of electronic and print media on the health status of patients was assessed with a 20-item questionnaire. Different demographic characteristics, such as age, gender, institution, position, and experience of respondents, were recorded. Quantitative data were analyzed with the use of Statistical Package for Social Sciences, version 20.0 (SPSS, Chicago, IL). The association of the demographic characteristics of the responses of physicians was determined by one-way ANOVA using 0.05 level of significance. RESULTS: In this study, 254 physicians provided consent to show their responses for research purposes. A response rate of 50.8% was obtained. Nearly one-third of the respondents negated that patients get health benefit using electronic and print media. The majority did not consider electronic and print media as lifestyle-modifying factors. Physicians thought that patients particularly do not rely on mass media for acquiring health information and consider healthcare professionals as unswerving information resource. CONCLUSIONS: Mass media can be productive resources to augment awareness among patients, although physicians seem unconvinced about the extended usage of print/electronic media.

Comparative bioavailability and pharmacokinetic study of Cefadroxil capsules in male healthy volunteers of Pakistan.

The current study was aimed to judge bioequivalence between two formulations of cefadroxil capsules as guided by FDA guidelines. Another objective was to conduct pharmacokinetic evaluation in Pakistani population. A single-dose, randomized, cross-over pharmacokinetic study was conducted during the month of May'2013 to August'2013. Washout period was one week. Fourteen healthy male adult volunteers were enrolled in the study, however twelve completed the study. Cefadroxil plasma concentration was analyzed by using validated HPLC method. Protein precipitation was achieved by the addition of 6% tri chloro acetic acid in 1:1 ratio and detection was done at 260 nm. Retention time was 7.792 min and correlation coefficient (R2) was 0.9953 showing linearity of the method. Blood sampling was carried out at different time intervals after administration of either test (TEST 500 mg) or reference (REF® 500 mg) formulation. Pharmacokinetic parameters (AUC0→ ∞, AUC0→ t, Cmax, Tmax, t1/2 and kel) were calculated using Kinetica® PK/PD software. The geometric mean ratios and 90% confidence interval (CI) of these pharmacokinetic parameters for cefadroxil (test and reference) formulations were 0.986 (90.83-106.98%) for AUC0→ t; 0.967 (89.13-104.92%) for AUC0→ ∞ and 0.999 (91.06-109.69%) for Cmax. The differences between Tmax of both formulations were not found to be statistically significant (p-value was more than 0.05). The 90% CI of the test/reference AUC and Cmax ratio of cefadroxil were within the FDA recommended range for bioequivalence. Maximum plasma concentration Cmax was 12.5 µg/ml for test and 12.47 µg/ml for reference formulations. Average time to reach Cmax for test and reference formulation was 1.54 and 1.5 hrs. The two formulations of cefadroxil studied during the above study were verified bioequivalent. Maximum plasma concentration of cefadroxil was lower than those mentioned in some previous studies, while Tmax and half-life were near to values reported in literature.

Determination of Cefadroxil in Tablet/Capsule formulations by a validated Reverse Phase High Performance Liquid Chromatographic method.

An innovative, selective and rapid reversed phase High Performance Liquid Chromatographic (RP-HPLC) method for the analysis of cefadroxil in bulk material and oral solid dosage forms has been developed and validated. The chromatographic system consisted of Sil-20A auto sampler, LC-20A pump and SPD-20A UV/visible detector. The separation was achieved by C18 column at ambient temperature with a mobile phase consisting of methanol: Phosphate buffer (10: 90) at a flow rate of 1.5 ml/min. The method is reproducible, repeatable (%RSD for intra-day and inter-day ranged between 1.75-5.33% and 0.58-2.69%) and linear (R2=0.9935). The LOD and LOQ of the method were 0.5 and 1.0 µg/ml, respectively. The present RP-HPLC method was found to be sensitive, accurate, precise, rapid and cost effective that can be efficiently used in QC/QA laboratories for routine analysis of the raw materials as well as oral dosage formulations of cefadroxil.

Disintegrants combination: development and optimization of a cefadroxil fast disintegrating tablet.

Fast Disintegrating Tablets (FDTs) is a rapidly growing dosage form preferred for special population (pediatric, geriatric and psychotic patients). It is also developed with the aim of improving bioavailability and patient compliance. During the present study, cefadroxil fast disintegrating tablets formulations (n=9) were designed and optimized by central composite design with two independent variables (croscarmellose and crospovidone) using design expert® software. The effects of independent variables on formulation properties such as friability, hardness, in vitro dispersion and disintegration were assessed by drawing response surface graphs with design expert® software. Tablets were assessed for pharmacopeial and non-pharmacopeial parameters to ensure the quality of compressed tablets. Among all formulations, F3, F8 and F9 have shown better results. The formulation F9 containing 15mg croscarmellose and 33.075mg crospovidone showed good pharmacotechnical attributes as well as shelf life. F 9 showed improved dissolution with t90% of> 2 min and will lead to better bioavailability.

Incidence of medication error associated with the use of beta-blockers in Pakistan.

Medication errors (ME) are human errors, which are very frequent in cardiovascular patients and result in patient morbidity and mortality. This study was focused to evaluate the quality of prescriptions and to emphasize the placement of clinical pharmacist in health care team. This study was carried out in different outpatient settings of (in) Karachi, Pakistan. The study period was June 2011 till June 2012. Retrospective data was analyzed for the outpatients' prescription of beta blocker drugs. During the study, prescriptions (n=450) were collected from different outpatient settings of (in) Karachi, Pakistan. Prescription containing beta-blockers were analyzed for the essential elements to be mentioned in prescription. Drug-drug interactions were identified by the Micromedex.2.0 Drug-Reax database and severity of medication error was determined by NCCMERP Index. A total of 1627 medication errors were identified in 450 prescriptions. The most frequent error was not mentioning the patient's weight (95%), followed by missing diagnosis (79.4%) and drug-drug interactions (69.5%). Twenty-two prescriptions were placed in the most severe category I (4.88%). Average number of drugs per prescription was 4.76. Significant difference was observed (χ(2)=52.418, p<0.05) using SPSS 19 for those prescription orders having more than 5 drugs with Beta-blockers. This indicates that the errors in prescription such as drug-drug interactions, wrong dose etc. was significantly increased with the number of drugs per prescription. Results showed that medication errors are very frequent in prescription written in outpatient setting of various hospitals and clinics in Karachi. This shows that the irrational prescribing is a common practice in developing countries. Placement of skilled pharmacist in the health care system is the only solution for avoidance of these medication related problems.

Emergence of resistance to fluoroquinolones among gram positive and gram negative clinical isolates.

Fluoroquinolones are broad-spectrum antibiotics that are considered as first line drugs to treat infectious diseases. In order to find out useful fluoroquinolones, the antibiotic resistance of fluoroquinolones, namely, ofloxacin (OFL), ciprofloxacin (CIP), norfloxacin (NRF), enoxacin (ENX), pefloxacin (PFL) and levofloxacin (LVF) was investigated against ninety five clinical isolates that includes Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus mirabilis. In vitro activity of these isolates was carried out by agar dilution method. All Staphylococcus aureus were sensitive to OFL at 2 µg/ml. About 6% isolates of Klebsiella pneumoniae were found to be resistance to LVF and ENX, 6% to CIP, OFL and PFL and none of the isolates were resistant to LVF and ENX. Percentage resistance of P. aeruginosa was found to be 4.35% to CIP, 7% to OFL and 2.2% to NRF, whereas 8.69% to ENX, 0% to PFL and 17.4% to LVF, respectively. The present study provides the data about the emergence of resistance to fluoroquinolones among gram positive and gram negative bacteria and strongly recommends the rational and appropriate use of these antibiotics.

Design and evaluation of a new formulation of enalapril maleate tablet.

Enalapril maleate, one of the Angiotensin converting enzyme (ACE) inhibitor is effective in the treatment of hypertension. Enalapril maleate is selected for the present study. The aim of this study was to develop a new formulation of Enalapril maleate tablet and its comparative evaluation with other formulations of Enalapril maleate tablet that are listed in the local index of registered pharmaceutical products. To accomplish this task, a new formulation of Enalapril maleate tablet has been developed by direct compression method. All formulation tablets with 5mg potency were selected and the new formulation tablets were also developed with 5mg potency. For new formulation as well as for six available formulations of Enalapril maleate tablets, various pharmaceutical parameters namely weight variation, thickness, hardness test; friability test, disintegration test, dissolution test and pharmaceutical assay were performed in accordance with United States Pharmacopeias (USP). The results of all the above tests were within the specified limits as mentioned in USP, whereas hardness test results for two formulations were deviated from the specified limits. It is concluded that direct compression can be used as an alternate method for the manufacture of Enalapril maleate tablet.