Evaluation of antibiotic utilization pattern and economic outcomes associated with surgical site infection in surgical department of tertiary care hospitals Karachi, Pakistan.

Surgical Site Infection (SSI) has an enormous impact on patients' quality of life. SSIs further stresses on allocation of different health care resources and contribute significantly in terms of high cost of care. This was a prospective study carried out in tertiary care hospitals of Karachi, Pakistan, involving abdominal surgeries and few other surgeries, in patients having 20 years of age and above, were admitted from June 2016 to May 2017. Total number of 554 patients were included. Data was collected in all relevant areas including utilization pattern of antibiotics, cost in term of infected and uninfected patients, the duration of patient stay etc. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) software. P value less than 0.005 was taken as significant. Single therapy of co amoxiclav or along with metronidazole and third generation cephalosporin were the most common prescribed antimicrobial groups. Amikacin most commonly used to treat post-surgical wound infection. Economic cost was high in terms of SSI patients. Duration of stay was found longer in infected patients. It can be concluded that SSI, may prolong length of hospitalization, cause morbidity, upsurge the health care cost and even may lead to mortality.

Quality-by-design based development of fast dispersible nimodipine tablets: Formulation attributes and release kinetic assessment.

In the present study fast dispersible nimodipine tablets were developed by direct compression method using quality by design (QbD) approach as per the central composite design by selecting avicel PH 102 (X1) and crospovidone (X2) as independent variables while % friability (R1), disintegration (R2) and hardness (R3) as output variables. Powder blends were assessed for flow characterization. At post compressional stage, several quality assessments were carried out. Particles morphology was observed using scanning electron microscopy (SEM). The stability study on the drug and optimized formulation were determined using thermal gravimetric analysis (TGA) and differential thermal analysis (DTA). RSM plots expressed the interaction of avicel PH 102 and crospovidone to determine the adequate quantities of excipients for the optimized formulation. Polynomial equations were used to validate the experimental design. The optimized formulations were evaluated for friability, disintegration and hardness. Results indicated that formulation (F4) containing avicel PH 102 (35%) and crospovidone (5%) was selected as best optimized formulation having friability 0.59%, disintegration 9 sec, % dissolution 95.703% and hardness 4.14 kg. Results of kinetics models indicated that all the developed formulations followed weibull model.

Formulation development of directly compressible mebevarine tablets using superdisintegrant: A way to investigate quality atributes, in vitro release kinetics and stability profile.

In order for preparing a solid oral dosage form, tablet quality is of significant concern. Compressibility behavior of different powders and mixtures of formulations and release pattern of any tablets are characteristic measures to define prerequisite quality attributes of any compressed formulations. There are basically two major methods that can be adopted for the preparation of tablets including granulation and direct compression. Later process offer fewer processing steps and agreeable release profile with acceptable quality parameters and hence preferred over granulation method. In this investigation Mebeverine hydrochloride an anti-muscarinic drug is studied for compression and release behavior using various concentrations of filler binders and disintegrants via rotatable central composite design (CCRD) option of design expert (software). Nine formulations were developed from F1 to F9 with Crospovidone (superdisintegrant) as (X1) (-α=1.17% to ± α=6.83%) and microcrystalline cellulose (Avicel 102, Filler/binder) as X2 (-α = 29.82% to ± α = 65.18%). Disintegration Time (DT) as (R1) and Hardness in (kg) as (R2) were determined as two dependent response variables. The performance of powder blends and formulations was analyzed by micromeritic and physico-chemical and assessments. Dissolution comparisons were statistically analyzed by ANOVA and model dependent and in-dependent methods. Best fit model was found to be Hixon-crowell's model (r2 = 0.995) followed by Weibull's model (r2 = 0.985). The Trial formulations F2, F4, F6 and F8 were also studied on accelerated conditions (40±5ºC 75%±5% RH) for stability tests and validity of the formulations in months were also determined between 35-39 months.

Exploration of clinical management system: Career ladders, working model and reforms; a cross sectional estimate from Karachi, Pakistan.

Clinical and hospital pharmacy services are not just medical and pharmaceutical sciences but also occupy significant placement in healthcare system. Pakistan is a developing state with a huge prerequisite for changes in the general wellbeing framework, specially hospital and clinical aspect of pharmaceutical services. The principal intention of this study is to analyze the services offered by different pharmacies in hospitals of Karachi in terms of infrastructure and personnel service qualities. The study was conducted in a cross sectional way that included stratified sampling technique. Reactions were broken down utilizing descriptive and inferential insights of measurements. The fundamental result procedures incorporated the scope of hospital pharmacy services, the general recruitment of clinical drug specialists (pharmacist), the product and equipment used in hospital pharmacy services, the background of staff (educational), acquisition of proficient training mode, practical involvement and experience. The clinical pharmacy facilities coverage mutually on the departmental scale (median =22.43%) and patient scale (median =17.25%) do not comply the 100% coverage that is obligatory for standard practices. In addition, 48.65% of the pooled hospitals data has shown absence of distinct administration rules for hospital and clinical pharmacists, and 45.33% lacks the use of rational drug software. It is concluded that important parameters like drug monitoring, medication records keeping; appropriate drug information software's and quality assurance in hospitals still need attention for better patient outcomes.

Formulation development and optimization studies of mouth dissolving tablets of tizanidine HCl.

The purpose of this research was the development and optimization of mouth dissolving tablets (MDT) of Tizanidine hydrochloride using superdisintegrant. MDTs of Tizanidine (4mg) were manufactured by direct compression method. Formulations comprised of Tizanidine and excipients including croscarmellose sodium, Avicel PH 102, aspartame, orange flavor and magnesium stearate. Blends of powder were assessed for flow characterization and then compressed by direct compression. During post compression stage, a detail evaluation of tablets with respect to weight variation, hardness, thickness, disintegration time, wetting time, friability, drug content analysis, content uniformity, palatability and dissolution studies was carried out. All the formulations complied with the pharmacopeial requirements of weight, disintegration time and assay. Amongst the trial formulations F4 with concentration of croscarmellose sodium i.e. 5% was proved as best optimized due to satisfactory quality attributes such as least disintegration time and sufficient hardness. Hence, it was concluded that manufacturing of mouth dissolving tablets by addition of superdisintegrant is beneficial for treating patients with dysphagia.

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.

Formulation development and in vitro evaluation of fast dispersible, taste masked aceclofenac compacted pellets.

The objective of study was to develop Aceclofenac fast dispersible compacted pellets with improved taste and fast drug release. Pellets were prepared by extrusion spheronization technique followed by direct compression to make compacted pellets. Formulations were comprised of sucrose, mannitol, ac-di-sol, aspartame, pine apple flavor and magnesium stearate. A mixture of distilled water and isopropyl alcohol (1:1) was used for wet massing. The effect of ac-di-sol on the drug release pattern was examined and dissolution profile comparison was established. All formulations followed First order and Weibull models and f2 values indicated dissimilarity with the marketed immediate release product. Taste of compacted pellets was evaluated by a panel of 12 human volunteers. Formulation P5 was found to be an optimized formulation due to satisfactory quality attributes.

Drug utilization evaluation of Piperacillin/Tazobactam: A prospective and cross sectional investigation in tertiary care setup.

Drug utilization evaluation (DUE) is an arrangement of continuous, orderly, criteria-based assessment of medication utilizes to guarantee that medicines are utilized suitably. In the event that treatment is regarded to be improper, provider and patient intervention may be important to optimize therapeutic efficacy. In the present study drug utilization evaluation of Piperacillin/Tazobactam was carried out in prospective manner. A well structured data collection form was constructed to collect the related information regarding demographic, clinical use, indication, culture sensitivity criteria, outcomes of therapy, renal impairment cases of dose adjustments and appropriate use. Results of chi square indicated insignificant relationship between gender and as p value was found to be p=0.446 and 0.111 for use of drug alone and in combination. Similarly insignificant relationship between gender and use of drug in combination with other antibiotics as p value was found to be p=0.111. It was found that from 61-70 years (Therapeutic Effectiveness; n=12, 9.37%), (Therapeutic Failure; n=10, 45.45%) and mortality (n=1, 50%) were quite higher. The prescription pattern was in accordance with standard guidelines. Study indicated need to elevate prescribers to pursue generic prescribing and rationally utilize antibiotics to avert advancement of resistance at the level of hospital and community. These sorts of studies are valuable for acquiring data about medication utilize designs and for recognizing inconceivable expense of medicines.

Development and validation of reverse phase HPLC method for determination of angiotensin receptor blocking agent irbesartan in plasma.

A sensitive, reproducible and modest analytical procedure was developed and validated for evaluation of irbesartan in human plasma. LLE (Liquid-Liquid extraction) of the drug was carried out with acetonitrile (1:1 v/v). Chromatographic separation of irbesartan was conducted by the help of 4.0mm × 25cm column having L1 packing from plasma and mobile phase utilizing HPLC. The mobile phase comprise of phosphate buffer and acetonitrile in a ratio of 67:33 v/v. The flow rate was set at 1ml/minute and the detector at a wavelength of 220 nm. The resolution of irbesartan was well performed from plasma components. This method was validated and demonstrated linearity with a concentration range of 0.1to 6µg/ml of irbesartan in plasma. Intra-day, inter-day accuracy was found 89.33% to 96.37% while intra-day, inter-day precision was found within the limit of 0.02 and 2.15 respectively. The mean recovery of irbesartan was 97.28%. The efficacy of extraction was proved by above-mentioned results. In plasma, the 0.05 and 0.1µg/ml dilutions were exhibited as the LOD and LOQ of irbesartan. Stability studies disclosed that irbesartan showed stability at -20°C storage.

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.

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.

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.

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.

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.

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.

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.

Estimation of simvastatin and cetirizine by RP-LC method: Application to freeze and thaw (FT) stability studies.

Sensitive, simple, reliable and rapid HPLC technique for the estimation of simvastatin (SMV) and cetirizine has been designed in this study. The chromatographic conditions were set using Shimadzu LC-10 AT VP pump, with UV detector (SPD-10 AV-VP). System integration was performed with CBM-102 (Bus Module). Partitioning of components was attained with pre-packed C-18 column of Purospher Star (5 µm, 250 x 4.6 mm) at ambient conditions. Injected volume of sample was 10 µl. Mobile phase was composed of 50:50 v/v ratio of Acetonitrile/water (pH 3.0 adjusted with ortho-phosphoric acid) having 2 ml/minutes rate of flow. Compounds were detected in UV region at 225 nm. Percent Recovery of simvastatin was observed in the range of 98-102%. All results were found in accept table range of specification. The projected method is consistent, specific, precise, and rapid, that can be employed to quantitate the SMV along with cetirizine HCl. It was estimated by 3 successive cycles of freeze and thaw stability. Results of FT samples were found within accept table limits the method was developed and validated in raw materials, bulk formulations and final drug products.