Dexibuprofen enteric film-coated tablets: design, characterization and pharmacokinetic analysis in human volunteers.

OBJECTIVE: This study aimed to develop a stable and scalable enteric film-coated tablet for the gastric irritant dexibuprofen. METHODS: Utilizing direct compression with super-disintegration (crospovidone), the optimal core batches were coated with Opadry white seal coat and enterically coated with Eudragit®L100 with pigment (Talc), demonstrating a 12% weight increase; release and integrity were assessed using specific pH buffers and SEM, with stability testing confirming a six-month shelf life at 40 °C and 75% RH. RESULTS: The optimized formulation achieved 99.87% release in phosphate buffer within 60 min, maintained integrity for 120 min in acidic conditions, and exhibited superior bioavailability compared to Innovifen with relative bioavailability ≈of 121% and elevated Cmax (18.35 µg/ml compared to 11.1 µg/ml). CONCLUSION: These results highlight the potential of this formulation to enhance patient safety and efficacy through delayed enteric technology and fast intestinal release.

Antimicrobial resistance pattern of Uro-Pathogens emphasizing non-lactose fermenting gram negative bacilli.

Objectives: To identify various species of non-lactose fermenting gram-negative bacilli involved in urinary tract infections, and to determine their antimicrobial resistance pattern. METHODS: The retrospective, descriptive, cross-sectional study was conducted from January 1 to April 1, 2022, at the Dow University of Health Sciences, Karachi, and comprised data from the institutional diagnostic laboratory that was related to urine samples regardless of age and gender from January 1, 2020, to December 31, 2021. Data was analysed using SPSS version 25. RESULTS: Of the 103,887 urine samples, 41,280(39.7%) were positive, 51,146(49.2%) showed no bacterial growth, 11,000(10.6%) had non-significant bacterial growth and 461(0.4%) had mixed bacterial growth. Of the positive samples, 18359(44.5%) were positive in 2020, and 22,921(55.5%) in 2021. Gram-negative lactose fermenting bacteria included escherichia coli 23,123(22.3%) and klebsiella pneumoniae 2,993(2.9%), gram-negative non-lactose fermenting bacteria included pseudomonas aeruginosa 1,110(1.07%), and gram-positive bacteria included enterococcus 8,008(7.7%). Pseudomonas aeruginosa was most resistant against tobramycin 880(79.3%) and least resistant against piperacillin-tazobactam 146(13%). CONCLUSIONS: Piperacillin-tazobactam was highly sensitive drug against non-lactose fermenting uro-pathogens.

Formulation of sumatriptan succinate orodispersible tablets using chitosan and sodium starch glycolate for immediate migraine relief.

Migraine is one of the common neurological disease affecting around 23% of the Pakistani population. Prompt treatment is required to regain the functional ability of patients. The present study was designed to develop sumatriptan succinate orodispersible tablets that would quickly overcome acute migraine episodes using 22 full-factorial design. The chitosan and sodium starch glycolate were taken as independent variables; friability, disintegration, dispersion time and water absorption ratio as response variables. Eight trial formulations were generated by Design Expert® software. The main effect plots were used to check the interaction of formulations with response variables. All trial formulations showed good micromeritic properties in terms of angle of repose (19.59o-24.57°), Carr's index (17.08-24.90%) and Hausner's ratio (1.20-1.33). The tablets wetted quickly (17.1- 39 sec) in dispersion medium, showed higher water absorption ratio (188-341 sec) and disintegrated quickly (13-20 sec) with an excellent dissolution rate (94-99%). The main effect plots show interactions between the independent variables against most of the study responses. A 22 full-factorial model was found to be effective in studying the influence of formulation variables on response parameters. Both chitosan and sodium starch glycolate can be used in combination to fabricate an effective orodispersible formulation of sumatriptan succinate.

Empagliflozin: HPLC based analytical method development and application to pharmaceutical raw material and dosage form.

The current investigation is based on efficient method development for the quantification of empagliflozin in raw and pharmaceutical dosage forms, as no pharmacopoeial method for the drug is available so far. The developed analytical method was validated as per ICH guidelines. C18 column with mobile phase (pH 4.8) consisted of 0.1% trifluoroacetic acid solution and acetonitrile (70:30 v/v) was used for drug analysis. The calibration plot showed good linear regression (r2>0.999) over the concentration of 0.025-30 µg mL-1. The LOD and LOQ were found to be 0.020 µg mL-1 and 0.061 µg mL-1, respectively. The percentage recovery was estimated between 98.0 to 100.13%. Accuracy and precision data were found to be less than 2%, indicating the suitability of method for routine analysis in pharmaceutical industries. Moreover, the drug solution was found to be stable in refrigerator and ambient room temperature with mean % accuracy of >98%. Empagliflozin contents were also tested in both the raw API and marketed tablet brands using this newly developed method. The mean assay of raw empagliflozin and tablet brands were ranged from 99.29%±1.12 to 100.95%±1.69 and 97.18%±1.59 to 98.92%±1.00 respectively. Based on these findings, the present investigated approach is suitable for quantification of empagliflozin in raw and pharmaceutical dosage forms.

Optimization of empagliflozin immediate release tablets (10 mg) using central composite rotatable design with response surface methodology.

Empagliflozin is a selective inhibitor of sodium glucose co-transporter II, given as mono therapy or an add-on treatment to reduce the glycated hemoglobin levels in type 2 diabetes. This work deals with designing, formulating and optimizing empagliflozin (10mg) immediate release (IR) tablets by direct compression technique using different excipients. Through central composite rotatable design (CCRD), total nine formulations (EF1-EF9) were generated by changing the composition of binder avicel PH 102® (X1) and superdisintegrant acdisol⌖ (X2). Formulation runs with in suitable weight range and powder properties were subjected to compression. The influence of interaction of excipients on friability (Y1), hardness (Y2) and disintegration (Y3) were analyzed by fitting the polynomial quadratic model with response surface methodology (RSM). Trials EF2, EF7, EF8 and EF9 exhibited acceptable tablet attributes upon physico-chemical testing. Different dissolution models were applied to observe the in vitro drug release pattern in phosphate buffer of pH 6.8. The cumulative drug release of IR tablet batches followed the Weibull kinetics with regression coefficient (r2) values of 0.983-0.992. Empagliflozin trials were exposed to accelerated storage conditions (40±2°C/ 75±5% RH) for stability testing. Shelf life period of exposed formulations were computed in range of 22 to 25 months. Keeping in view of the results, it is concluded that the employed technique of preparation and optimization are observed to be excellent for developing immediate release empagliflozin (10mg) tablets.

Hepatoprotective and antioxidant activity of Dicliptera bupleuroides Nees. extracts on paracetamol induced hepatotoxicity in rats.

Aim of this study to evaluate the safety profile, hepatoprotective and in-vivo antioxidant activities of Dicliptera bupleuroides Nees. Toxicity studies were conducted in human RBCs and DNA by using standard procedures. Acute hepatoprotective investigation was carried out in albino rats by treated with all six fractions of D. bupleuroides 350 mg/kg/day. ALT, AST, ALP and total bilirubin (TB) were performed. The n-hexane fraction (200 mg/kg/day) exhibited appropriate hepatoprotective activity hence subjected to chronic study (14 days). Paracetamol induced the hepatotoxicity (350mg/kg) and silymarin (50 mg/kg) was standard drug. Liver function tests, liver peroxidation tests and histopathological examination were performed at the end. Hexane fraction showed significant decrease in the level of ALT (88.1±7.8), AST (93.8±7.6), ALP (136.3±8.4) and TB (0.6±0.03) as compared to the standard drug (p>0.05). Rats treated with ethyl acetate fraction showed decrease in MDA (42.8±0.7) while GSH was found to be increased (107.7±1.8) against the toxic group (51.3±2.9), (73.6±4.0) respectively. All the drug extracts decreased the oxidative stress and protect the DNA from free hydroxyl radicals. DNA damage protection activity of these fractions is due to phytochemicals present in these fractions. These results indicate that the plant fractions possess significant hepatoprotective and antioxidant activities with no toxic effects.

Formulation optimization, in vitro characterization and stability studies of sustain release tablets of Ketoprofen.

The aim of the current study was to formulate sustain release (SR) tablets of ketoprofen. Five batches (batch I -V) of matrix based ketoprofen tablet were prepared by dry granulation method using hydroxyl propyl methyl cellulose (15000cps). Compatibility of formulation excipients with drug was explored through FT-IR technique. Various physical and chemical parameters of all tablet batches were evaluated with multi-point dissolution profile (for 24hrs) for formulation optimization. Release kinetics of trials was estimated by model dependent and independent methods. Formulations having excellent quality attributes were then compared with marketed ketoprofen SR tablets. Accelerated stability study was also conducted to compute the shelf life of the optimized formulation. FT-IR scans illustrated the compatibility of ketoprofen with all tablet excipients. On the basis of testing results and controlled release pattern batch II was set to be an optimized trial having shelf life of 37 months. All trial batches (batch I-V) and the marketed brand exhibited highest linearity towards zero order and Korsmeyer-Peppas model with non-fickian anomalous transport (n=0.541-0.655).

Stability and in vitro release kinetic studies of cinitapride (1mg) mouth dissolving tablets.

Cinitapride has been widely given in gastro-esophageal reflux disease (GERD) and dysphagia due to irregularities of GI motilities. Mouth dissolving tablets were prepared for rapid availability and action of drug. Multi-point dissolution studies were conducted in 0.1 N HCl solution of pH 1.2 and phosphate buffer of pH 4.5 and 6.8. Drug release profile showed higher liberation of cinitapride at lower pH then basic medium (<80%). Formulation containing crospovidone (10%) was found to be optimized trial having excellent quality pharmaceutical attributes. The lowest AIC, highest MSC and regression (> 0.9) values were observed for Weibull kinetics in all dissolution medium reflecting the excellent model fitting for the present study. Accelerated stability testing data showed excellent results of drug assay (>99%) along with physical characteristics indicating the absence of drug degradation as well excipient interaction. The estimated shelf life period of various optimized trial formulations was found in between 33 to 41 months.

Preparation of microemulsion containing Lycopersicon esculentum extract: In vitro characterization and stability studies.

Lycopene, the active component of Lycopersicon esculentum species, has been reported for the protecting capabilities against ultra-violet induced skin pigmentation, antioxygen and antityrosinase activities. In the present study, extract of tomato fruit was obtained from the Lycopersicon esculentum plant using solvent system comprised of hexaneethanol-acetone. The phyto chemical active constituent lycopene was then identified by spectrophotometric technique at 470nm. Micro emulsions were developed containing different ratio of water, isopropyl myristate (oil), tween 80 and propylene glycol as surfactant and co-surfactant respectively via pseudoternary phase diagram. Various physicochemical tests were performed including globular size, conductivity, viscosity, scanning electron microscopy (SEM), refractive index (RI) and pH measurement for the formulation characterization. Results of physical and chemical stability studies showed that the micro emulsion with proportion of surfactant: co-surfactant of 2:1 (Smix) was found to be optimized formulation and with enhanced stability. Therefore, concluded that the stability of the micro emulsion was dependent on the proportions of surfactant co-surfactant, water and oil in the preparation.

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 (X1) microcrystalline cellulose (Avicel PH-102) (18-51%), (X2) methocel K4M (0.1-25%) and (X3) 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.

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 be 217869.7PKR 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.

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 λmax of 261nm. The drug showed the good linearity from 20 to 60µg/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 <1 was computed for inter and intraday analysis indicating the high accuracy and precision of the developed technique. The developed method is robust because it shows no any significant variation in with minute changes. The LOD and LOQ values were assessed to be 2.2µg/mL and 6.6µg/mL respectively. The investigated method proved its sensitivity, precision and accuracy hence could be successfully used to estimate the CPM content in bulk and pharmaceutical matrix tablets.

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.

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 0.978-0.998. 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.

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-5 was 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.

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.

Assesment 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.

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.

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 (MA9 and MB9) and tests (MA2, MA4, MA6, MA7 and MA8 (15 mg) and MB2, MB4, MB6, MB7and 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.