Open Access Original Research Article

Formulation, Characterization and in-vitro Evaluation of Famciclovir Loaded Solid Lipid Nanoparticles for Improved Oral Absorption

Pavan Kumar Rawat, Chandra Kishore Tyagi, Sunil Kumar Shah, Arun Kumar Pandey

Journal of Pharmaceutical Research International, Page 1-17
DOI: 10.9734/jpri/2020/v32i2930879

Famciclovir loaded Solid Lipid Nanoparticles (SLNs) using triglycerides as solid lipids were successfully prepared using the double emulsion-solvent evaporation technique. Formulation parameters like amount and type of lipid and level of surfactants affected the nanoparticle characters. It was observed that nanoparticle characters like average particle size and distribution, drug content, entrapment efficiency and release pattern were dependent on these formulation variables. The optimized formulations depicted the desired characters of low particle size, in the range of 140-170 nm in case of Glyceryl monostearate (GMS) and glyceryl distearate (GDS) SLNs and 250-340 nm in case of glyceryl behenate (GB) SLNs and entrapment efficiencies in the range of 35-48%. In vitro drug release was extended upto 8 h and the release profile was explained by the Baker-Lonsdale model for spherical particles. Morphological examination by Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) displayed homogenous solid, spherical and non- porous particles. The formulations depicted good redispersibility after lyophilization and presence of residual solvents in the formulations within the prescribed limits suggested suitability of the preparation technique. Freeze- dried formulations were found to be stable in terms of particle size and drug loading even after 6 months of storage at refrigerated conditions.

Open Access Original Research Article

Computational Exploration of Potential Polo-Like Kinase 1 Inhibitors as New Chemotherapeutic Agents

Mubarak A. Alamri, Ahmed D. Alafnan

Journal of Pharmaceutical Research International, Page 18-30
DOI: 10.9734/jpri/2020/v32i2930880

Background and Objective: Polo like kinase-1 (PLK-1) enzyme belongs to serine/threonine protein kinase family that is regarded as a principle mitotic controller of G2-M phase transition. The antimitotic therapies are a cornerstone for the treatment of metastatic as well as benign cancer. Therefore, PLK-1 has recently gained much interest in the field of targeting it by novel and effective inhibitors.

Materials and Methods: The present study described the used of pharmacophore modelling based on the potent and selective clinical agent, Volasertib and followed by hybrid selection of a kinase inhibitors databank of 4800 diverse compounds by pharmacophore- and docking-based virtual screening.

Results: The retrieved hits were filtered on the bases of their pharmacophore-fit scores, docking binding affinity scores, ADME-T profiles as well as ligand quality assessments. Among the five hit compounds that fulfil the criterion, three compounds, Z1991791422, Z56115729 and Z1991791176 were selected for binding dynamic analyses by molecular dynamic simulation. The Z1991791422 and Z56115729 compounds illustrated stable binding behaviours at the proposed binding site. Conclusion: Thus, these compounds might emerge as potent inhibitors of PLK1 and could be applied as seeds for designing better PLK1 inhibitors in near future.

Open Access Original Research Article

A Tetra-Primer Amplification Refractory Mutation System–Polymerase Chain Reaction (T-ARMS-PCR) for Genotyping of rs8099917 & rs12979860 IL28B Polymorphisms and Its Correlation of Various Variables in Iranian HCV Patients

Ali Bahari, Mohammad Hashemi, Gholam Reza Bahari, Tahereh Fakharian, Sina Gerayli, Abbas Esmail Zadeh, Hamid Reza Sima, Hooman Mosannan Mozaffari, Ali Reza Bakhshipour, Zohreh Bari

Journal of Pharmaceutical Research International, Page 31-41
DOI: 10.9734/jpri/2020/v32i2930881

Background: Selecting patients for new direct acting antiviral treatment of HCV has prompted a conflicting matter worldwide because of its high cost and limited availability. Genotyping of IL28B polymorphisms will aid clinical decision making for identifying priorities of urgent treatment in resource-limited countries.

Objectives: The aim of the present study was to design a simple tetra-primer amplification refractory mutation system–polymerase chain reaction (T-ARMS-PCR) for genotyping of the rs8099917 and rs12979860 IL28B gene polymorphisms. Furthermore, we identify the correlation of variables such as gender, serum ALT level, histology of liver and baseline viral load with these polymorphisms.

Patients and Methods: We efficiently designed a T-ARMS-PCR for detection of rs12979860 and rs8099917 IL28B gene polymorphisms. Using this method, we genotyped 148 hepatitis C patients. To ensure T-ARMS genotyping quality, we, regenotyped samples with the PCR- sequencing method.

Results: Results of genotyping of rs12979860 and rs8099917 by T-ARMS PCR method were 100% concordant with the sequencing results. Among these 148 patients with chronic hepatitis C, the frequency of the rs12979860 CT, TT and CC genotypes was 72.3%, 14.2% and 13.5%, respectively and the frequency of the rs8099917 TT, GT and GG genotypes was 58.1%, 38.5% and 3.4%. Low frequency (2.7%) of association of two unfavourable homozygous genotypes (TT rs12979860 / GG rs809917) as well as 56.7% of association of 3 or 4 favorable alleles could explain good response of Iranians to HCV treatment with interferon-based regimens. About correlation of polymorphisms with different variables, only high viral load showed a statistically significant correlation to unfavorable genotype of TT rs12979860 ( p value = 0/05 ) and there was no correlation of  serum ALT level, gender and  histology of liver to IL28B genotypes.

Conclusions: We report that rs8099917 polymorphisms could predict outcomes better than rs12979860 in Iranian HCV patients.

Open Access Original Research Article

Acute Renal Problems Still a Great Challenge in Obstetrics

Madiha Abbasi, Erum Samreen, Naheed Parveen, Shafaq Nazia, Farah Naz

Journal of Pharmaceutical Research International, Page 42-47
DOI: 10.9734/jpri/2020/v32i2930882

Objective: To assess the early risk factors and outcomes of the patients presented with acute renal issues, at tertiary care Hospital.

Methodology: This descriptive study was conducted at gynaecology and obstetrics department of Liaquat University of medical and health Sciences. Study duration was six months from June 2019 to November 2019. Women having age more than 18 years, developed renal impairment as serum creatinine level more than 1.2 mg/dl were included. All data was collected via self-made proforma. SPSS version 20 was used for the data analysis.

Results: Total 58 women having renal problems during pregnancy were studied, their mean age was 28.40+4.68 years and mean gestational age was 28.40+4.68 years. Most of the women 70.2% were un-booked. Parity 1-3 was commonest. Anaemic women were on high risk of renal impairment as most of the patients had moderate anemia. Hypertension was in 35.1% patients, placental abruption was in 10.5% cases, tow patients had diabetes, 12.3% presented with pregnancy induced hypertension and postpartum haemorrhage was in 05.3% cases. There was a significant negative correlation between haemoglobin level and serum creatinine level, (r-value 0.029).

Conclusion: Anemia was the commonest reason for renal impairment during pregnancy. Most of the women were un-booked, having high parity and were presented with anemia. This morbidity can be decreased and prevented by stabilizing the haemoglobin level by taking proper antenatal care.

Open Access Original Research Article

Extracted Trans-Resveratrol from Arachis hypogaea Enhances Expression of Sirtuin Gene and Replicative Life Span in Saccharomyces cerevisiae

Mritunjay Kumar Singh, Ravi Deval

Journal of Pharmaceutical Research International, Page 48-59
DOI: 10.9734/jpri/2020/v32i2930883

Aims: Biotic stress given by Aspergillus niger enhances trans-resveratrol production in Arachis hypogaea plant. This plant extract  increases sir2 gene expression and Replicative Life Span in  Saccharomyces cerevisiae.

Design of Study: Peanut plant was grown in aseptic environment, infected by Aspergillus niger. Plant extract used for quantification of trans-resveratrol by RP-HPLC. Yeast culture was grown in Potato dextrose media along with plant extract. Sir2 gene expression fold calculated by real time pcr. Replicative Life Span of yeast was measured by spectrophotometer.

Place and Duration of Study: Allele Life Sciences Pvt. Ltd., Department of Biotechnology between February 2017 to March 2020.

Methodology: Biotic stress in Arachis hypogaea plant was induced by wounding the leaves and introducing Aspergillus niger to enhance trans-resveratrol production. Tran-resveratrol was quantified by Reverse Phase High Pressure Liquid Chromatography (RP-HPLC). Two methods conducted to check reverse ageing, first one epigenetic based, when extracted trans-resveratrol from infected Arachis hypogaea plant extract added to Saccharomyces cerevisiae culture, it enhanced expression of Sir2 gene in Saccharomyces cerevisiae measured by qPCR, ABI applied biosystem. Process included RNA isolation, cDNA synthesis and thereafter qPCR. Enhanced expression of sirtuin responsible for gene silencing as sirtuin (Sir2 gene product) is a class of Histone deacetylase transferase enzyme. Second method, Replicative Life Span of Saccharomyces cerevisiae culture increased when Aspergillus niger infected peanut plant extract added to yeast culture which was measured through spectrophotometer at 600nm and showed high absorbance value.

Results: Tran-resveratrol was quantified by Reverse Phase High Pressure Liquid Chromatography (RP-HPLC) and yield was 2.24 mg/g. Sir2 gene expression increased by 1.56 fold in yeast grown in infected peanut plant extract. Absorbance of yeast culture grown in infected peanut plant extract was 0.522±0.008 which was higher than control.

Conclusion: Sir2 gene expression enhances along with replicative life span in yeast in presence of peanut plant extract.

Open Access Original Research Article

Menstrual Irregularities Frequency in Reproductive Age Women with Chronic Parenteral Viral Hepatitis and Insufficiency of Antioxidant Factors

M. A. Rashidova, L. F. Sholokhov, M. A. Darenskaya, S. I. Kolesnikov, L. I. Kolesnikova

Journal of Pharmaceutical Research International, Page 60-66
DOI: 10.9734/jpri/2020/v32i2930884

Background: Our previous study of the lipid peroxidation and antioxidant defense system (LPO-AOS) state in women with chronic viral hepatitis (CVH) showed the content of fat-soluble vitamin alpha tocopherol significant reduction. Reproductive health of women with CVH needs special attention. The objectives of this study was to determine the frequency of menstrual disorders in the group of women with CVH with marked alpha tocopherol insufficiency.

Study Design:  A case-control study.

Place and Duration of Study: A study was conducted at Scientific Centre for Family Health and Human Reproduction Problems and in the hepatological department of the Irkutsk clinical hospital of infectious diseases from 2010 to 2014. This work was performed with the use of equipment of Collective research centre “Center for the development of progressive personalized technologies for health” SC FHHRP, Irkutsk.

Methods and Results: Our study included 44 reproductive age women with CVH and comparable age 28 healthy women. All women underwent clinical examination and questionary survey. We found alpha tocopherol insufficiency in 95.5% cases of patients with CVH and menstrual disorders.

Conclusion: Our results suggest that menstrual disorders in patients with CVH may be associated with alpha tocopherol insufficiency.

Open Access Original Research Article

Association between Subclinical Hypothyroidism and Albuminuria in Patients with Type 2 Diabetes Mellitus: A Cross Sectional Study in Iran

Atousa Najmaldin, Solmaz Askari, Majid Foroutan

Journal of Pharmaceutical Research International, Page 67-75
DOI: 10.9734/jpri/2020/v32i2930885

Introduction: Studies have shown the association between subclinical hypothyroidism and type 2 diabetes. However, the common complications of type 2 diabetes, such as diabetic nephropathy and albuminuria with subclinical hypothyroidism, are not fully clear yet. This study thus aimed to determine the association between subclinical hypothyroidism and albuminuria in patients with type 2 diabetes mellitus.

Methods: This was a cross-sectional study, of 140 individuals diagnosed with type 2 diabetes mellitus (DM) admitted to the internal clinics of Kosar Hospital in Semnan, Iran in 2017-2018. The participants were selected, and were compared based on having 2 TSH levels above normal (>4.2 mIU/L) 3 months apart, as well as patients were divided to two groups including, subclinical hypothyroidism group (n=40) and euthyroid group (n=100) based on demographic information, laboratory information and indicators such as albuminuria, and urinary albumin-to-creatinine ratio (UACR).

Findings: The mean and standard deviation of UACR in patients with subclinical hypothyroidism were significantly higher than those of euthyroid patients (46.09 ± 27 9.27 vs. 3.94 ± 0.24 and P = 0.015, respectively). In patients with subclinical hypothyroidism, there was a statistically significant and direct relationship between UACR values with primary TSH level (r = 0.555, P< 0.001) and UACR values with secondary TSH level (r = 0.563, P< 0.001).

Conclusion: Among type 2 DM patients, the rate of albuminuria in subclinical hypothyroidism group was significantly higher than that of euthyroid patients and with increasing initial and recurrent TSH levels, UACR values and consequently albuminuria increased.

Open Access Original Research Article

Effect of Sitagliptin and Glimepiride on Pancreatic Beta-Cells during the Treatment of Type-2 Diabetic Mellitus by Statistical Analysis

Bhaskar Joshi, Praveen Yadav, A. Geetha Bhavani

Journal of Pharmaceutical Research International, Page 76-83
DOI: 10.9734/jpri/2020/v32i2930887

Aim: The study aimed to analyze the effect of Sitagliptin with Glimepiride during the treatment to improve pancreatic beta-cells in T2DM patients. Beta cells are type of cell found in pancreatic islet and also synthesize, secrete the insulin and amylin. Sitagliptin is found to be maintaining the beta-cells function and glycaemic control in T2DM patients.

Place and Duration of Study: Sample: This study open label randomized T2DM patients, study was conducted at the, Felix multi-specialty hospital, Noida U.P with enrolled patients from 1st Oct, 2017 to 30st Sept, 2019.

Methodology: Randomly diabetes mellitus type-2 (T2DM) patients’ data is collected (110patients) for statistical analysis. For this study T2DM patients enrolled with age of 30-60 years, treated with Sitagliptin and Glimepiride once a day. The baseline of HbA1c >7.0% to <10.5% thus, the performed student t-test is to find out the significance role.

Results: The 110 patients are distributed in two groups: one Sitagliptin user group (n=62) and second Glimepiride user group (n=43). The sitagliptin treatments may also protect also beta cells as pancreas may not able to regenerate beta cell.

Conclusion: The sitagliptin treatments may also protect beta cells as pancreas may not able to regenerate beta cell.

Open Access Original Research Article

Discovery of Carbonic Anhydrase Inhibitors through Molecular Docking as Novel Anticancer Agents

Ahmed Alharbi, Waleed Mansi Alshammari, Turki A. K. Alreshidi

Journal of Pharmaceutical Research International, Page 84-91
DOI: 10.9734/jpri/2020/v32i2930886

The cancer is the world's most silent and life-threatening diseases, which may arise in most common people without any indication at any age and result in uncontrolled growth and metastasis. In the current manuscript, we targeted the discovery of novel carbonic anhydrase IX inhibitors. The discovery is based on computational techniques based on direct and indirect drug design. We screened nearly 500000 compounds from the zinc database to identify the top 1000 compounds with indirect drug design techniques while the top 200 were docked for the interactions and scoring functions. The top 12 out of these were reported in the manuscript, which showed higher binding scores than the standard compounds with selectivity based on interaction. These leads may be the future drugs for anticancer agents through carbonic anhydrase inhibitors.

Open Access Original Research Article

Maternal Near Miss in a Tertiary Care Hospital

Sanjay Kumar Patil, Ashitosh Bahulakar, S. S. Vhawal, Guvari Ragunath, Sanjay M. Jadhav

Journal of Pharmaceutical Research International, Page 92-96
DOI: 10.9734/jpri/2020/v32i2930888

A hospital-based observational study was performed with 250 patients to assess the incidence of near-miss maternal related to extreme obstetric problems or maternal disease and near-miss mortality level institutional maternal. A majority of patients were from middle class (78%) followed by lower class (12%) and upper class (10%). Hypertension in pregnancy was diagnosed in 40% patients, while 12% and 6% patients had diabetes mellitus and cardiac diseases respectively. The gestational age at delivery was between 37-41 weeks in 64%, followed by 36% delivering before 37 weeks. The live birth rate was 68% while fresh still birth and macerated still birth was 22% and 10% respectively.

Open Access Original Research Article

A Study on Haematological Profile in Clinically Suspected Cases of Neonatal Sepsis

S. R. Upadhey, Avinash M. Mane, Atul B. Hulwan, Rohit S. Kadam, Dhirajkumar Mane

Journal of Pharmaceutical Research International, Page 97-101
DOI: 10.9734/jpri/2020/v32i2930889

The present study was a two year observational study of haematological profile in clinically suspected cases of neonatal sepsis. Study analyzed the haematological findings according to Rodwell’s haematological scoring system in neonates clinically suspicious of having sepsis. It included 108 neonates admitted in NICU of our hospital during the study period of June 2015 to May 2017. According to clinical findings, Rodwell’s hematological score and blood culture positivity 108 neonates were divided into three groups; proven sepsis, probable sepsis and no sepsis. Study show that Rodwell’s haematological scoring system is a simple, quick, cost effective tool which can be used as screening test for early diagnosis of neonatal sepsis.

Open Access Original Research Article

Molecular Modeling and Docking Studies of Some Benzodiazole Derivatives on the Protein of Staphylococcus aureus

A. S. Sony, Xavier Suresh

Journal of Pharmaceutical Research International, Page 102-110
DOI: 10.9734/jpri/2020/v32i2930890

In this work, molecular modeling and docking studies of antimicrobial heterocyclic compounds were carried out using Auto Dock. Docking studies were carried out for Benzodiazole derivatives to study their affinity to Cell wall anchored (CWA) protein of Staphylococcus aureus. The docking studies of the compounds showed binding energies ranging from -7 to -5 kcal/mol against clumping factor A (ClfA), a CWA protein of Staphylococcus aureus, [PDB file:1N67]. Molecular modeling and docking studies of Benzodiazole derivatives show that the main action of the compounds is inhibition of cell wall adhesion.

Open Access Original Research Article

Neonatal Outcome in Meconium Stained Amniotic Fluid

Narendra P. Porwal, Danesh B. Potdar, Rashmi Kanvikar, Suryakant Y. Ingle

Journal of Pharmaceutical Research International, Page 111-115
DOI: 10.9734/jpri/2020/v32i2930891

Meconium stained amniotic fluid (MSAF) is a commonly studied topic in neonatal outcomes. Meconium was commonly thought a precursor to eventual or active fetal death, although, some scholars do not consider this to be connected with foetal hypoxia, fetal acidosis, or trauma. Purpose of the study was to identify various maternal risk factors leading to meconium staining of amniotic fluid. The study was conducted in KIMSDU, Karad for a duration of 18 months. In this study the neonates with meconium stained amniotic fluids were classified into two groups based on type of staining (thin-MSAF and thick-MSAF). Most of the babies with MSAF had birth weight between 2.6-3.5 kg (64.65%) followed by 1.6-2.6 kg (25.57%) and then ≥3.6 kg (9.78%). Number of babies requiring newborn intensive care unit (NICU) admission were 66 in case of thick meconium and 42 in case of thin meconium. In this study the overall neonatal mortality was 0.86% among MSAF cases. Among MAS cases, mortality was 25.87%. The study outcomes were statistically correlated using Chi-square test to validate the significance of the results.

Open Access Original Research Article

Development and Validation of Simple, Rapid and Sensitive High- Performance Liquid Chromatographic Method for the Determination of Butenafine Hydrochloride

Mohammad Javed Ansari, Mohammed Muqtader Ahmed, Md. Khalid Anwer, Mohammed F. Aldawsari, Saad M. Al Shahrani, Niyaz Ahmad

Journal of Pharmaceutical Research International, Page 116-125
DOI: 10.9734/jpri/2020/v32i2930892

Aims: The current paper reports a simple, rapid, sensitive, accurate, and precise Reverse-phase high performance liquid chromatography (RP-HPLC) method with wide range of estimation to determine butenafine hydrochloride in nanosponges. This method has been validated as per ICH norms.

Study Design:  Experimental design with influence of variables such as mobile phase composition, flow rate, temperature and wavelength on the chromatographic peaks.

Place and Duration of Study: Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia between Jan 2020 and March 2020.

Methodology: Separation was achieved by utilizing the most commonly used reverse phase column (C-18, 5 μm, 150 mm x 4.6 mm) set at 30ºC and quantified by UV detection at 280 nm after isocratic elution from a mobile phase (70:30 v/v of methanol: phosphate buffer pH 3.0) flowing at 1 ml/min.

Results: A sharp and symmetrical peak was observed at 4.08 ± 0.01 minutes. The low variation in peak area and retention time (1.12% and 0.29%, respectively) and a high number of theoretical plates (>2000) indicated this method’s efficiency and suitability. The least square linear regression analysis (Y = 9265.5 X + 1961.4) showed excellent correlation (r2 = 0.999 ± 0.0003) between concentration and peak area of butenafine hydrochloride through a wide concentration range of 1–50 µg/ml. The limits of detection and quantification (LOD and LOQ) were 0.18 µg/ml and 0.57 µg/ml, respectively. The assay or determinations were accurate, precise and reproducible with mean accuracy and mean relative standard deviation of precision of 101.53 ± 0.43% and 0.51 ± 0.11% respectively.

Conclusion: The developed RP-HPLC method was simple, sensitive, reproducible with wide range of estimation of butenafine hydrochloride in the nanosponges. The proposed method could be used for the analysis of butenafine hydrochloride in the conventional pharmaceutical formulations such as tablets, syrup, creams including novel formulations such as nanoparticles, nanosponges, nanoemulsions. The proposed method overcomes the specificity, sensitivity and reproducibility related issues of ultraviolet-visible spectroscopy.

Open Access Original Research Article

Umbilical Cord Blood Culture in General in the Diagnosis of Sageis Newborns

Naredra P. Porval, Kanvikar Reshmi, D. B. Potdar, S. B. Karanjkar

Journal of Pharmaceutical Research International, Page 126-131
DOI: 10.9734/jpri/2020/v32i2930893

Worldwide neonatal sepsis is among the most frequent causes of neonatal death. Various studies have tried to establish the relationship between prevalence of neonatal septicemia risk factors and bacteriological profiling, low birth weight, prematurity, etc. Current study was aimed to compare early onset of neonatal sepsis (EONS) among primigravida and multigravida mothers using umbilical cord blood (UCB) and peripheral venous blood (PVB) samples. It was also aimed to establish the utilization of umbilical cord blood culture (UCBC) in comparison to peripheral venous blood culture (PVBC) in identifying EONS. In present study the blood samples were collected from high risk neonates for the clinical blood culture and screening. Among the 75 neonates in the study, 24 (32.0%) were observed to have sepsis screen positive. Study of high risk neonates umbilical cord blood culture (UCBC) positivity was 17.3% while Peripheral Venous blood culture positivity was 5.3%. Moreover,  in this study all risk factors like Prematurity, Low birth weights, Premature rupture of membrane, and birth asphyxia were significantly (p<0.05) associated with UCBC growth/positivity. Low birth weight (86%) was mostly reported in the high risk neonates with other associated sepsis factors. Similarly maternal fever and prolonged rupture of membrane was highly significantly (p<0.01) associated with UCBC positivity. Gram negative bacterias  were  more  commonly found,  such as Pseudomonas (5.3%), followed by E. coli (4%), and Klebsiella (2.7%) and gram positive Streptococcus sp. (2.7%), etc. From our analysis it can be said that the UCBC has strong diagnostic outcomes as compared to the PVBC for etiological evaluation of bacterial sepsis in neonates at high risk.