Journal of Pharmaceutical Research International

Aim: In December 2019, there were reports of a new type of coronavirus that affects the different health systems of the world. We have carried out a systematic review of the possible antivirals studied that could be useful in this public health catastrophe.

Data Sources: A search strategy with MESH terms was performed in PubMed, Web of Science, and Scopus. Also, RCTs published in clinicaltrials.gov were reviewed. The databases were searched between April and June 2020.

Study Selection: We selected all Randomized Controlled Trials evaluating the effects of antivirals and 5 studies were included from a research database of 280 articles collected between. After removing duplicated articles, 43 were selected for review. Finally, 5 articles were eligible for full-text review and included in the article.

Results: Current randomized controlled trial data showed no clinical improvement in terms of mortality, need for oxygen support or need for intubation in patients who used antivirals versus those who did not. No clinical improvement was demonstrated. It was observed that there is difficulty in calculating clinical improvement, this large difference makes the eligible studies difficult to compare.

Conclusion: These predictors, however, need further work to validate reliability. More clinical trials involving antivirals are needed to observe a relationship between clinical improvement or mortality from SARS-CoV-19.

The essential oil extracted by hydrodistillation from the aerial parts of Origanum vulgare L. harvested in the region of Skikda (North-East-Algeria) gave an excellent oil yield (2.8%). Its analysis by Gas Chromatography–Mass Spectrometry (GC/MS) identified 98.10% of its constituents. The major components are: carvacrol (47.6%), thymol (16.6%), p-cymene (13.5%) and γ-terpinene (11.2%).

The aim of this study was to the preservative effect of Origanum vulgare essential oil applied to a very low concentration of 0.025% (minimum inhibitory concentration (MIC)), of a sensitive food of essential nutritional value, of great consumption and easily perishable “minced meat”, stored at different times, namely: T₀ = 0 min, T₁ = 40 min, T₂ = 24 h, and T₃ = 48 h. By studying its microbiological quality by determining the rate of reduction of the total aerobic mesophilic microflora and of Staphylococcus aureus. The addition of Origanum vulgare essential oil to minced meat allowed a highly significant reduction of 0.01<p<0.1 in total aerobic mesophilic microflora reduction rate and very highly significant (p≤0.01) for Staphylococcus aureus, and markedly increase the shelf life. This allows us to propose the use of this essential oil as a source of natural preservative substances.

Aim: The aim of our present work was to develop and validate a reverse phase high-performance liquid chromatography (RP-HPLC) method for the simultanious determination of Decitabine (DEC) and Cedazuridine (CED).

Methodology: The developed method was further applied to observe the degradation of analytes under the influence of different forced degradation conditions. Analytes were resolved on C18, 250 x 4.6 mm, particle size 5 µm Xterra column, using a mobile phase combination of 0.1% Ortho Phospharic Acid buffer pH 6.5: Methanol (40:60v/v) with flow rate of 1mL/min and injection volume of 10 µL. Quantification was carried out with PDA detector at an isosbestic point of 220 nm with a linear calibration curve in the concentration range of 35-175 μg/mL for DEC and 100-500 μg/mL for CED.

Results: Validation of the developed method was performed as per ICH guidelines viz., linearity, accuracy, precision, and robustness. The limits of detection (LOD) and the limits of quantification (LOQ) for CED were found to be 2.69 µg/mL and 8.15 µg/mL respectively. LOD and LOQ for DEC 1.55 µg/mL and 4.68 µg/mL respectively. Moreover, validated method was applied to study the degradation profile of analytes under various stress degradation conditions.

Conclusion: The proposed method was found to be sensitive, specific and was successfully applied for the simultaneous estimation of Decitabine (DEC) and Cedazuridine (CED) in bulk drug, and tablets.

A series of substituted 4-{1-aza-2-[(aryl) amino)]}-3-methyl-2-pyrazolin-5-ones has been synthesized and evaluated for their biological activity. The title compounds (4a-l) were prepared by the diazotization of substituted anilines (1a-l) to form substituted phenyl hydrazine derivatives (2a-l) which synthesized substituted 4-{1-aza-2-[(aryl) amino)]}-3-methyl-2-pyrazolin-5-ones (4a-l) by Michael addition reaction, which is a nucleophilic addition of enolate anion to the carbon-carbon double bond of a α, β–unsaturated carboxylic acid derivatives. Twelve different pyrazolinone derivatives (4a to 4l) were synthesized. Structural assignments of these compounds have been made by elemental analysis, FTIR, ¹HNMR and Mass spectral data and the purity of the compounds was determined by TLC. The antifeedant activity of the newly isolated heterocyclic compounds was evaluated against agriculture pest Achoea janata. Compound 4d found to be very effective as antifeedant while rest of the compounds showed a moderate to good degree of antifeedant activity.

Background: Pseudomonas aeruginosa is a clinically important pathogenic microbe in hospitalized patients. It is a major cause of mortality and morbidity having a number of mechanisms that make it antibiotic resistant. Considering the dearth of antimicrobial drugs to treat infection with this pathogen, it has become a necessity to open up new arena for treatment with this organism. Recently, there has been an up rise in the number of multidrug resistant pathogenic strains of Pseudomonas aeruginosa.

Objective: Isolation and identification of multidrug resistant Pseudomonas aeruginosa from wound specimens and to evaluate the antibiotic resistant strains of this microbe.

Methodology: One hundred and fifty clinical samples of wound were taken from hospitalized patients at Jinnah hospital Lahore during the period of October 2019 to April 2020. In total, twenty (20) isolates of Pseudomonas aeruginosa were identified using the cultural features, morphological characteristics and various biochemical tests plus the Vitek 2 system. Blue/green, brown /blue and yellow/green pigment production showed the presence and growth of Pseudomonas aeruginosa.

Results: Percentage of Pseudomonas aeruginosa in females came out to be 15% as compared to 11.42% in males. This was followed by testing susceptibility of isolates of Pseudomonas aeruginosa to various antimicrobial drugs. Piperacillin/tazobactam and meropenem showed the highest efficacy against Pseudomonas aeruginosa. Highest resistance was exhibited against trimethoprim/sulfamethoxazole which was 75%.

Conclusion: Most isolates showed multidrug resistance to four or more drugs. Development of multidrug resistance has emerged as a global problem with pathogens commonly causing infections becoming increasingly resistant to antimicrobial agents.

Objective: To detect treatment outcomes in current smokers, ex - smokers and nonsmokers, in newly diagnosed pulmonary TB patients.

Methodology: This cohort prospective study was conducted in the department of Microbiology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre Karachi, with the collaboration of different (DOTS) centers of Pathology Karachi Medical and Dental College, Karachi. All newly diagnosed pulmonary TB patients registered for treatment either of gender were included. The patients were divided into three groups. Group-A: Current smokers, Group-B: Ex-smokers, Group-C: Non-smokers. Patients were followed for 6 months. Outcome was assessed in terms of cured or failure. All the information was enrolled in pre-designed proforma. Data was analyzed by using SPSS version 20.

Results: In current study mean age of non-smokers was 44.20±17.73, ex-smokers 43.13±15.67 years mean age of smokers was 38.07±15.67 years. Males were in majority in all study groups as in ex-smokers group, males were 98.75%, non-smoker males were 90.0% and in smoker group males were 92.50%. At starting of treatment, mean weight of smoker patients was 55.50±5.41 kg, ex-smoker’s 48.91±9.00 kg and mean weight of non-smokers 48.71±7.04 kg. P-0.001. At starting of treatment, the mean ESR of non-smokers was 89.31±10.02, ex-smoker’s was 82.62±12.18 and smokers ESR average was 80.61±15.83. P-0.001. After 6 month treatment, cured rate was (96.25%) in non-smokers, (90%) in smokers and (93.75%) in ex–smokers.

Conclusion: This study concluded that cured rate was high in non-smokers. Smoking status in individuals greatly affects the tuberculosis treatment outcome with enhance failure rate.

Aim: To develop a stability indicating Rp-UPLC method for the simultaneous determination of Lamivudine, Dolutegravir and their degradants in tablets.

Methodology: The chromatographic separation was performed on BEH Shield RP18 (2.1 mmX100 mmX1.7 mm) using a isocratic mobile phase Potassium dihydrogen orthophosphate pH 3 adjusted with orthophosphoric acid: methanol (30:70,% v/v) at a flow rate of 0.5ml/min. Column was maintained at room temperature and eluents are monitored at 258 nm.

Results: Retention times of the analytes were found to be at 0.81 and 2.78 mins for Lamivudine and Dolutegravir respectively. The calibration of peak area versus concentration, which was linear from 105 to 315 µg/ml for Lamivudine and 17.5 to 52.5 µg/ml for Dolutegravir, had regression coefficient (r²) greater than 0.999. The method had the requisite accuracy, precision and robustness for simultaneous determination of Lamivudine and Dolutegravir in tablets.

Conclusion: The proposed method is simple, economical, accurate, precise and can be successfully employed in routine quality control for the simultaneous analysis of Lamivudine and Dolutegravir in pharmaceutical formulations.

Background/ Aim: Pregnancy induced hypertension (PIH) has been a leading cause of maternal mortality worldwide. It could be responsible for several complications like hemodilution, altered lipid metabolism and deficiencies of different minerals in body. Although the causes of Pregnancy induced hypertension (PIH) remains indistinct. The aim of our present study was to evaluate the changes in magnesium serum levels and lipid profile in hypertensive and normotensive pregnant women.

Materials and Methods: An analytical case control study comprising 60 individuals was designed. From which 30 normotensive pregnant women served as control group (A) and 30 pregnancy induced hypertensive women served as case group (B). Patients with pre-existing hypertension were excluded.

Results: The independent t-test was used for comparison of various parameters between group A and B. Triacylglycerol (TAG) and low density lipoprotein cholesterol (LDL-C) levels were significantly high in PIH (B) as compare to normotensive group (A). Mean serum values of TG were measured as (195.73 ± 70.28 vs 156.27 ± 55.60 mg dL^-1) and LDL-C vs control (87.33 ± 37.74 vs 69.45 ± 28.58 mg dL^-1) in PIH and normotensive groups respectively. HDL-C in PIH vs Control (47.40±1.12 vs 54.43 ±1.27 mg dL^-1) and Mg⁺² PIH vs control (1.36±0.07 vs 1.94±0.35 mg dL^-1) were measured respectively. High density lipoprotein cholesterol (HDL-C) and magnesium Mg⁺² levels were significantly reduced in PIH.

Conclusion: The lower serum magnesium levels and abnormal lipids profile may indicate their possible role as risk factors in the development of PIH in pregnant women. Hence initial diagnosis of hypomagnesemia in PIH cases may help in minimizing the complications and development of new cure strategies.

Background: Paracetamol overdose is a predominant cause of hepatotoxicity and nephrotoxicity in both humans and experimental animals. There is an emerging focus on plant products to find a highly effective and reliable drug for the prevention of paracetamol –induced toxicity.

Objective: In this study, we investigated the Hepatoprotective and Reno-protective Effects of artichoke (Cynara scolymus L.) Leaf extract and rosemary (Rosmarinus officinalis L.) extract against paracetamol Induced toxicity in Albino Rats.

Materials and Methods: Rats were divided into five groups: Negative control, paracetamol (1000 mg/kg dose) PCT, artichoke leaf extract “ALE” (1.5  g/kg, orally + paracetamol for 30 d), rosemary extract “RE” (125  mg/kg + paracetamol for 30 days) and the last group was treated with PCT+ ALE+ RE for 30 days.

Results: Paracetamol caused marked liver damage as noted by significant increased activities of serum aminotransferases, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase. Paracetamol also raised serum levels of urea, creatinine, and Cystatin-C. In addition, there was a significant decrease in serum total protein and albumin. Paracetamol caused an elevation in lipid peroxidation paralleled with significant decline in reduced glutathione (GSH) level and activities of glutathione-S- transferase (GST), glutathione (GPX) peroxidase, and superoxide dismutase (SOD) in the liver and kidney. These results are confirmed in the histological examination of the liver and kidney.

Conclusion: Treatment with artichoke leaf extract (ALE) and rosemary extract (RE) produced a potential protection of the liver and kidney against biochemical and histological alterations and oxidative stress induced by paracetamol.

The objective of this study is to evaluate the physicochemical parameters of Piroxicam 20 mg Tablet brands. A comparative qualitative research study was conducted for a period of six months. A total of five different brands of active Piroxicam tablets were selected. All samples were purchased from various local markets of Larkana Sindh. These collected samples were coded as PIX01, PIX02, PIX03, PIX04 and PIX05 for minimalism. Specific physicochemical quality control lab tests included Aesthetic test, Diameter and Thickness test, Weight variation, Mechanical strength and Friability test were performed on each sample according to standards and results were compared. Packing of all samples was observed according to GMP guidelines. Data was analyzed by using statistical software SPSS 24.00. Most of the brands were within official limits of United State Pharmacopeia (USP) except brand PIX05 showing variation in hardness test, whereas two brands PIX03 and PIX05 fail in friability test as well as powder material seen inside of blisters in aesthetic test. Dissolution test for each brand of Piroxicam was performed in which PIX02, 04 and 05 failed. It was concluded that from this study after in vitro physical evaluation of various brands of Piroxicam tablets, most of the brands are being manufactured under compliance of GMP guidelines as well as specifications described under USP. Traces of powder material inside of blister in aesthetic test and unsatisfactory result in friability and hardness test in same brand indicating the deviation of GMP guidelines and USP specification which may cause the out of specification result in chemical test.

Aims: As no data is available in Pakistan so the aim of current study is to find out the link of multiple risk factors with recurrent pregnancy loss (RPL) in Pakistan.

Study Design: Case control study.

Place and Duration of Study: Study conducted in Obstetrics and Gynecology Clinic of Benazir Bhutto Hospital, Holy Family Hospital Rawalpindi and Polyclinic Hospital Islamabad from November 2018 to April 2019.

Methodology: Subjects were investigated on the basis of an in depth Performa. For data analysis Statistical package for social sciences version-20 was used. Beside this, height in cm, weight in kg and blood pressure in mmHg were recorded. All the statistical calculations were performed by using SPSS 20. For association analysis of qualitative variables Spearman bivariate correlation was calculated while for numerical variables ANOVA was applied. Multinomial logistic regression model was used and the odd ratio and relative risk were calculated.

Results: Among cases 91.34% were having spontaneous miscarriage and majority (64.86%) were during first trimester. Spearman bivariate correlation reported a strong association of recurrent pregnancy loss with the risk factors including family history, smoking, obesity, history of hypertension and history of diabetes, having highly significant p-values, on the hand, significant association of maternal age with the frequency of recurrent pregnancy loss was found but not with the paternal age and parity. The multinomial logistic regression model showed that smokers were19.012 times more prone to develop recurrent pregnancy loss.

Conclusion: The multiple risk factors including maternal age, obesity, smoking, family history, body mass index, hypertension and diabetes have a strong association with the recurrent pregnancy loss. So keeping these risk factors in mind a careful evaluation of each pregnancy is necessary to reduce the risk of recurrent pregnancy loss.

We have carried out a survey among Healthcare professionals in the perceptions and attitude towards COVID-19 and also attempted to reach a few conclusions in the form of recommendations.  A questionnaire based online survey was conducted between 1^st April 2020 and 30^th May 2020. 97.20% (p<0.05) participants suggested that protective mask for the patients or attendants should be made compulsory while coming to the Hospitals. 79.33% (p<0.05) think that post COVID-19 the area outside the doctor’s chamber should not be crowded and some measures should be taken in order to reduce the number. In the same line, 83.58% (p<0.05) participants favour, limiting the number of attendants with the patients and making a prior appointment compulsory, 51.97% (p<0.05) wish to switch to virtual counselling. Considering the variation in strains of the virus, different geographical conditions, demography, economic status and healthcare facilities, a uniform policy shouldn’t be implemented all across the globe or even for a country.

Background: Liposome offers many advantages over conventional dosage forms, like increased bioavailability, possibility of releasing drug at slower and constant rate, accurate drug release. Docetaxel is approved by the FDA for the treatment of locally advanced or metastatic breast cancer, head and neck cancer, gastric cancer. Docetaxel is BCS Class 4 drug; hence efficacy can be improved with liposomal formulation.

Objectives: The Present study prepared Docetaxel loaded liposomal formulation.

Materials and Methods: Formulation batches were designed on the basis of solvent, lipid to cholesterol ratio, lipid to release modifier ratio, hydration temperature and various physicochemical and morphological properties of formulation were examined. The zeta potential, particle size determination, pH, stability, determination of encapsulation efficacy, morphology of formulation and in-vitro drug release were investigated.

Results:  The zeta potential values of FD5 and FD9 were found to be -12.6 to -12.9 mV and -10.6 to -11.9 mV respectively. The entrapment efficiency of formulations of batch FD5 and FD9 were found to be 83.20% and 85.22% respectively. By comparing both FD5 and FD9 it was found that FD9 batch is optimized than FD5 in all aspects.  The formulation batch FD9 has particle size of 105 nm, zeta potential in range of -10.6 to -11.9 mV; Drug entrapment efficiency 85.22%, Assay of formulation was 99.56 % and FD9 formulation shows extended release of Drug up to 13 hours.

Conclusion: The study confirmed that the Liposome formulation was successfully prepared and evaluated.

Aims: Edoxaban is a direct-acting oral anticoagulant, being a highly selective, direct and reversible factor Xa inhibitor. Edoxaban is used to treat and prevent blood clots such as deep vein thrombosis and pulmonary embolism. The dried spot technic, including dried blood spots and dried plasma spots, is used in many fields, from newborn screening to monitoring of therapeutic drugs in toxicology. In this case, equipment with a highly sensitive detector, such as a mass spectrometer, is required, as well as conditions for a high degree of drug recovery from the dried spot. In this work, the extraction of edoxaban from dried plasma spots (DPS) was studied to determine the optimal parameters of the extraction method.

Study Design: Analytical experimental study. Short Research Articles.

Place and Duration of Study: Core Facility of Mass Spectrometric Analysis, Institute of Chemical Biology and Fundamental Medicine SB RAS, between August and October 2020

Methodology: The organic extraction method was selected for evaluation as the most suitable for LC-MS analysis. Several parameters were investigated to find the best combination for extracting edoxaban from DPS for further LC-MS analysis: percent organic solvent, presence or absence of 0.1% formic acid (FA), extraction time, volume, and temperature.

Results: The results showed that the extraction was influenced by the composition and volume of the solvent, but not temperature and time. Pure acetonitrile is the worst solvent for extracting edoxaban from DPS. The most optimal parameters are MeOH: 0.1% FA in H₂O (70:30, v:v) solvent with an extraction temperature of 40 °C, an extraction time of 15 minutes and a solvent volume of 50 μl.

Conclusion: Several solvents suitable for LC-MS analysis can be used to recover edoxaban from DPS.

The aim of this study is to assess the association of periodontal disease and COVID 19. Coronavirus have been announced pandemic along the globe by the WHO, which have severely affected every countries healthcare framework and health care profession­als globally. Due to this pandemic every individual facing severe problems both economically and emotionally. The similarity seen on inflammatory response pathway shows there is a potential relationship between COVID-19 and Periodontitis are related. Considering the relationship, significant importance should be given to maintain periodontal health, maintaining careful and good oral hygiene in the COVID-19 situation. There is also chance of feasibility that periodontal disease can be susceptible for an individual’s COVID-19 unfavourable outcomes. This relationship shows the interrelation among periodontal disease and COVID-19 and between the cytokine relationship which advices in improving hygiene in oral cavity during this COVID situation. And it is found individuals with periodontal disease have high risk of getting COVID associated unfavourable consequences.