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.

The psychology of Suicide: From research understanding to intervention and treatment.

Suicide is considered one of the major causes of death across the globe. The rate of suicide has increased in the recent past and has become a serious problem globally, with nearly one million people committing suicide every year which represents a global standardised rate of 11.4 per 100,000 population i.e., 15 for males and 8 for females.1 From 2000 to 2016, the age-adjusted suicide rate has grown by 30%. Individuals generally have history of mental trauma and distress before attempting suicide. Rate of suicidal ideation is more than that of committing suicide. It is evident that the topic of suicide needs to have a global priority. As clinicians and researchers, it is pivotal responsibility of mental health professionals to establish prevention and intervention programmes to reduce the risk of suicides.

Availability and use of Automated External Defibrillators in Karachi, Pakistan: A cross-sectional study.

OBJECTIVE: To assess the availability and use of automated external defibrillators in various public and private establishments, and to assess knowledge, attitude and practices related to its use. METHODS: The telephone-based survey was conducted from March to August 2019 in Karachi after approval from the ethics review committee of the Aga Khan University, Karachi, and comprised public and private establishments identified through purposive sampling based on the standard requirements for automated external defibrillators installation. Data was collected using a predesigned questionnaire which was pilot-tested for reliability and validity. Data was analysed using SPSS 23. RESULTS: Of the 53 establishments, 32(60.4%) were private and 21(39.6%) were public. Overall, 9(17%) establishments were aware of automated external defibrillators and 1(1.9%) had an automated external defibrillator on the premises. Also, 25(47.2%) establishments believed that having an automated external defibrillator on the premises would be useful, while 25(47.2%) were undecided. Besides, 22(41.5%) establishments said they would consider installing an automated external defibrillator on the premises, while 24(45.3%) were undecided. Finally, 37(69.8%) establishments expressed a positive desire to get trained in giving basic life support. Conclusion: There was a need for a city-wide automated external defibrillator placement project for a reduction in mortality due to out-of-hospital cardiac arrest.

Development of stress-induced cardiomyopathy after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Pseudomyxoma Peritonei, a massive mucinous peritoneal collection due to a rare epithelial neoplasm, can be effectively treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC). A 43-year-old female, previously treated for mucinous ovarian carcinoma with CRS-HIPEC, and total abdominal hysterectomy and bilateral salpingo-oophorectomy, presented with new-onset abdominal distension and early satiety. She was diagnosed with Pseudomyxoma Peritonei. After 48 hours of treatment with CRS-HIPEC, she presented haemodynamically unstable with acute chest pain. Electrocardiogram showed broad complex tachycardia with ST depression in leads V3-6. Severe systolic dysfunction with Ejection Fraction (EF) of 20% along with severe pulmonary hypertension, visualized on Echocardiography. A diagnosis of Stress-induced Cardiomyopathy was established using InterTAK Diagnostic Score. Patients with CRS-HIPEC have presented with Stress-induced Cardiomyopathy. However, no specific relation between the two has been established. This case report discusses Stress-induced Cardiomyopathy as a complication of CRS-HIPEC.

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.

The circlet effects of Covid-19 pandemic and major crisis faced by developing nation: Now and beyond.

COVID-19 has taken over the world as the largest viral outbreak in the past 100 years. With over 13 million confirmed cases and 0.5 million-plus people dead, it has affected the life around us. With Pakistan being amongst the top 15 countries affected by it, the government of Pakistan has started vaccination, issued SOPs on daily life and smart lockdown continues in the country, but a part of this activity developing countries are still facing even greater difficulties in handling this crisis. This paper was designed to evaluate the status of scientific literature available on Covid-19 pandemic and to relate this situation from Pakistan perspective. A detailed review of published literature was conducted from March 2020 to August 2020. Covid-19, pandemic, Pakistan, healthcare setup, psychological impact, educational activities and challenges SOPs were utilized as key vocabulary. Miscellaneous searching tools including, Science Direct, Embase, PubMed, Google Scholar and Covid-19 portal from Government of Pakistan were visited for relevant information. A total of 30 research commentaries, articles, opinions and editorial letters were selected based on the required information. This article discusses the effects of COVID-19 on society and focus on SOPs introduced and their effects on the physical and mental health of the general public.

Review: Herbs, Immunity and nCOVID-19: Old performers in new Pandemic.

The novel coronavirus (nCOVID-19) has spread to endless nations and turn out to be a pandemic around the globe. Because of the developing number of affirmed cases and open public hazard owing to its high risk of infection rate, it has expected a lot of consideration from world health organizations and national health regulatory and monitoring agencies. The world is in surge to explore or discover novel treatment options and vaccine that can lead to cure. There is no proven effective treatment for nCOVID-19 however along with available antiviral therapy Chinese researchers recommended herbal treatments as effective and alternative treatments options to treat this pandemic. Herbal products are wealthy in dynamic phytochemicals, such as the terpenoids, various collection of flavonoids, sulfides, lignans constiuents, coumarins concentrates, saponins moities, polyphenolics composite, numerous alkaloids, polyines, furyl mixtures, proteins and related compounds, thiophenes and peptides groups. In this review we discussed pathogeneis, immunity and current herbal treatment strategies of nCOVID-19 to cure this world wide pandemic.

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.

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.

Suppressor of cytokine signaling-3 in pregnant females with or without hypertension.

Suppression of Cytokine Signalling-3 (SOCS-3) modulates the inflammatory pathways responsible for vascular stability. Therefore, we aimed to estimate SOCS-3 levels in 2nd trimester pregnant females and correlate it with blood pressure. A case control study recruiting (n=111) females was conducted at the Aga Khan University. They were classified as pregnancy induced hypertensives ornormotensive as per American College of Obstetricians and Gynecologists Guidelines. Weight, Body mass index, lipid profile and blood glucose were recorded while SOCS-3 was measured by ELISA. Higher SOCS-3 levels were seen in hypertensive group (30 pg/ml) versus normotensive (16 pg/ml). Both Systolic & diastolic blood pressure (r=0.520; p <0.001) (r=0.490; p <0.001) showed an independent significant positive correlation with SOCS-3 level. It is safe to suggest that SOCS-3 has an association of causing high blood pressure. However, more research needs to be conducted to establish a mechanism and chronological order to these events in a pregnant female.

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 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.

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.

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.

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.

Development and validation of RP- HPLC method with UV detection to determine and quantify dimenhydrinate in human plasma.

A simple, sensitive and rigorous method for estimation of dimenhydrinate in human plasma was searched and its validation was carried out. LLE (Liquid-Liquid extraction) of analyte with mixture of Hexane and ethyl acetate (1:1 v/v) was carried out for the preparation of Plasma Samples, Chromatographic elution of dimenhydrinate was conducted in human plasma and mobile phase with C-18 bonda Pack column (10µm; 250 × 4.6), using a mobile phase consisting a solution of ammonium bicarbonate in water and methanol at a flow rate of 0.5ml/minute with UV detection at 229 nm. The resolution of dimenhydrinate was well performed from plasma components. This method was validated and exhibited linearity with concentration range of 6 to 380ng/ml of dimenhydrinate in plasma. The Intra day precision was 89.2 to 96.89% and Inter day precision was 88.6% to 93.26%, the average recovery of dimenhydrinate was 97.02%. The efficacy of extraction was proved by above mentioned results. 2ng/ml and 6ng/ml, were appraised as the LOD and LOQ of dimenhydrinate, stability studies disclosed that dimenhydrinate exhibited stability in Plasma after Freeze & thaw cycles and upon -20°C storage, the method was developed well.