Open Access Original Research Article

Critical Factors for Metformin Osmotic Controlled Release Pump

García-Flores Mirna, Melgoza-Contreras Luz María, Hernández-Baltazar Efrén

Journal of Pharmaceutical Research International, Page 1-12
DOI: 10.9734/jpri/2020/v32i3530974

Aim: Studied the critical factors in the design of an osmotic pump with metformin release rate constant at 4%/hr in diabetes mellitus within 24 hr. with the goal to reduce daily medications.

Study Design: Experimental design 32

Methodology: In vitro drug release profiles for 24h. The effects of different formulation variables, that is, concentration of hydrophilic polymer, diameter of drug releasing orifice and coating thickness, on the drug release profile were investigated. Also, the impact of pH, osmotic pressure and morphology with stereo microscopy and scanning electronic microscopy of the osmotic pumps were investigated. At last, osmotic pumps surface was analyze with scanning electronic microscopy.

Results: Metformin osmotic pump were successfully prepared in this study to overcome the weak point of multiple doses and great concentration fluctuation of metformin. The formulation determined finally have a release orifice of 700 mm and 3.0% of weight gain, achieved the desired effect which can realize the constant drug release rate at the first 24 hr.

Conclusion: The developed osmotic systems have a linear release near 4%/hr. and demonstrated that the behavior was independent of the agitation intensity and the pH of the gastrointestinal apparatus.

Open Access Original Research Article

An Efficient and Inexpensive PEI-mediated Transfection for Transient Overexpression of CYP2C9 in WRL 68 Normal Liver Cells

Nurliana Abd Mutalib, Akmal Arif Daud, Hasseri Halim, Normala Abd Latip

Journal of Pharmaceutical Research International, Page 13-21
DOI: 10.9734/jpri/2020/v32i3530975

Aims: This study aims to develop an efficient, and inexpensive transfection procedure using low cost polyethylenimine (PEI) as transfection reagent for overexpression of CYP2C9 in WRL 68 host cells.

Introduction: Overexpression of CYP450 isozymes such as CYP2C9 has been a reliable approach in developing a high specificity in vitro tool for inhibition study of this liver enzyme. Transient or stable transfection are used to insert plasmid DNA into a mammalian host cell in order to produce proteins. There are many efficient transfection reagents available in the market for this purpose, however, it can be expensive, and a low-cost alternative is favorable.

Methodology: Cytotoxicity of PEI was screened on four cell lines namely WRL 68, HepG2, MCF-7 and A549 using MTS assay. WRL 68 was transiently transfected with CYP2C9 plasmid using PEI and DNA concentration as well as transfection time was optimized for the best efficiency and expression. Expression of CYP2C9 protein was measured using qPCR and further evaluated with western blot analysis.

Results: IC50 values of PEI are 0.327 ± 0.013 mg/mL (WRL-68), 0.395 ± 0.037 mg/mL (HepG2), 1.159 ± 0.032 mg/mL (A549) and 1.281 ± 0.000 mg/mL (MCF-7). Combination of 3ug plasmid DNA with 2.8 μM of PEI and 10.5 mM NaCl resulted in the highest transfection efficiency and expression after 48 hours.

Conclusion: A low-cost and efficient PEI transient transfection procedure was optimized for CYP2C9 overexpression and useful for the purpose of further development of cell-based enzyme inhibition model.

Open Access Original Research Article

Elucidating Anti-Acne Properties of a Novel Herbal Moisturizer

Abdul Hafeez, Shmmon Ahmad, Anmar Al- Taie

Journal of Pharmaceutical Research International, Page 22-27
DOI: 10.9734/jpri/2020/v32i3530976

Acne vulgaris is most common dermatological condition that affects more than 70% of teenagers and more than 10% of adults. The moisture content of human skin makes it appear young and primary function of moisturizer is to avoid the dehydration by preventing the moisture loss. Natural therapies are more suitable and they are more reliable with less or no side effects. The current research focused on the use of herbs for treating acne vulgaris as a moisturizer. This research focused on the use of Azadirachta indica, Curcuma longa, and Ocimum sanctum to prepare the formulation, Azadiracta indica, Ocimum sanctum and Curcuma longa possessed the significant capability for inhibiting acne. The antimicrobial activity was evaluated against the Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium by disc diffusion method. Prepared formulations were tested for physical parameters such as pH, spreadability, viscosity and color. Formulation studies was found to optimum for all parameters. The study showed the anti-acne moisturizer was significantly effective in controlling the bacteria which cause acne, i.e. Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium. From this research, can be inferred that formulated herbal anti-acne moisturizer was related with a substantial decrease in the growth of microbes that causes acne.

Open Access Original Research Article

Specifics of Treatment of Hyperuricemia with Febuxostat and Its Effects on Concentrations of Total, LDL and HDL Cholesterol, Compared to the Conventional Treatment with Allopurinol

Nermina Ziga Smajic, Selma Skrbo, Naida Omerovic, Kemal Duric, Mirza Dedic, Anela Hadzifejzovic Trnka, Belma Pehlivanovic, Dina Lagumdzija, Fahir Becic

Journal of Pharmaceutical Research International, Page 44-54
DOI: 10.9734/jpri/2020/v32i3530978

Hyperuricemia is a potential marker of cardiovascular diseases, and its relation to hypertension and arteriosclerosis, as well as the outcomes of certain cardiovascular events, is interesting. The research was carried out a sample of 50 subjects of both sexes, who were either on allopurinol or febuxostat treatment. Effects of allopurinol and febuxostat on concentrations of uric acid and some lipid fractions (total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol) were observed in 25 subjects on allopurinol treatment, and in 25 subjects on febuxostat treatment, who were chosen by defined criteria, with each patient serving as his or her control. The total observation period was six months and the cut was made after the first three months and at the end of the research. Evaluating the effectiveness of allopurinol in subjects with hyperuricemia, it was established that concentrations of uric acid decreased by 126.28±20.36 µmol/L, at the end of the research, compared to the initial concentration. In subjects who used febuxostat, at the end of the research, concentrations of uric acid decreased by 252.80±94.17 µmol/L, compared to the initial concentration. Evaluating the effectiveness of febuxostat on concentrations of lipid fractions, a statistically significant increase of 0.17±0.02 mmol/L in concentrations of HDL and a statistically significant decrease of 0.37±0.14 mmol/L in concentrations of LDL were noted. Subjects with gout treated with allopurinol had significantly lower average concentrations of cholesterol compared to subjects with gout and metabolic syndrome (p=0.001). Subjects with gout and metabolic syndrome had significantly higher concentrations of LDL at the beginning and the end of the research, regardless of therapy (p=0.045;p=0.049, respectively). Both drugs showed effectiveness in the treatment of hyperuricemia, and a certain effect on concentrations of lipid fractions.

Open Access Original Research Article

Box-Behnken Design Approach for Optimization of a Liquid Chromatographic Method for the Determination of Anti Leukemic Drugs in Bulk and Pharmaceutical Formulations

R. Suresh, M. Swamivelmanickam, S. Sivakrishnan

Journal of Pharmaceutical Research International, Page 67-77
DOI: 10.9734/jpri/2020/v32i3530980

To develop and validate a RP-HPLC method for the determination of selected anti- leukemic drugs in bulk and pharmaceutical formulations using Design of experiments. Development of the chromatographic method is based on design of experiments (DOE) approach, utilizing two level full factorial design for screening and Box-Behnken experimental design for optimization. In order to identify the significant parameters for the optimization, by simultaneously registering the main, interaction and quadratic effects of three factors such as volume of methanol (X1), concentration of buffer(X2) and flow rate (X3) on the selected responses like capacity factor K1 of first eluted peak  (Y1), resolution of critical peaks RS (1,2) (Y2) and amp; RS (2,3) (Y3) and retention time of last peak tR4 (Y4) as responses. Analytes were separated on a Onyx monolithic- C18 (100×4.6mm) with mobile phase comprising Potassium dihydrogen orthophosphate (0.01M), Methanol and Acetonitrile in ratio of (30:34.29:35.71), with flow rate of 0.723 mL/min and pH 3.5 adjusted with dilute orthophosphoric acid. Total chromatographic analysis time per samples was approximately 5 minutes with DST(IS), IMT, IBT and SFN eluting with retention times of 2.64, 3.05, 3.81 and 4.59 minutes respectively. Calibration curves were linear over selected range 0.997 for the all analytes. The method was sensitive with the LODs were 10.457, 13.07 and 26.169 ng/mL and LOQs were 31.68, 39.6 and 79.3ng/mL for IMT, IBT and SFN respectively. Inter and Intra-day precision data (in terms of %RSD) was fond to be less than ≥3 respectively, Recoveries ranged ≥102±2% for Imatinib- Gleevec, Ibrutinib- Imbruvica and Sorafenib- Nexavar. The obtained results corroborated the potential of the proposed method for determination of all the three anti-leukemic drugs for routine analysis for products of similar type and composition.

Open Access Original Research Article

Tetrapleura tetraptera of Ghanaian Origin: Phytochemistry, Antioxidant and Antimicrobial Activity of Extracts of Plant Parts

Christopher Larbie, Felix Charles Mills- Robertson, Emmanuel Bright Quaicoe, Rita Opoku, Naomi Chounbayor Kabiri, Rachel Owusu Abrokwah

Journal of Pharmaceutical Research International, Page 78-96
DOI: 10.9734/jpri/2020/v32i3530981

Introduction: The role of medicinal plants in meeting the healthcare needs of the populace, particularly in developing countries cannot be overemphasized. They provide holistic treatment and wellbeing due to a plethora of phytochemicals found in them. Among such is Tetrapleura tetraptera (Schum. & Thonn.) Taub., a multipurpose tree plant with varied biological activities. The current study was aimed at assessing the basic phytochemical constituents, free radical scavenging activity as well as the antimicrobial effect on various solvent extracts of leaves, fruit and stem bark of T. tetraptera of Ghanaian origin.

Materials and Methods: Aqueous, 50% hydroethanolic and methanolic extracts were made from the leaves, fruits, and stem bark of T. tetraptera. They were assessed for the qualitative and quantitative phytochemical constituents, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, antimicrobial activity as well as the spectroscopic properties (Ultraviolet – visible and Fourier-transform infrared spectroscopy). Compounds in the methanolic extracts were evaluated using the gas chromatography–mass spectrometry.

Results: Tannins, reducing sugars, coumarins and flavonoids were present in all extracts while hydroethanolic and methanolic extracts were rich in phenols, tannins and flavonoids, especially for the stem bark. Leaf extracts had better antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Candida albicans and Proteus mirabilis.

Conclusion: Generally, leaves and stem bark extracts of T. tetraptera are rich in biologically active phytochemicals, supporting their use in ethnomedicine and could be exploited further for other biological activities.

Open Access Original Research Article

Impact of Socioeconomic Inequalities on Child Malnutrition

Zamir Ahmed Qambrani, Asif Nadeem Jamali, Habibullah Siyal, Sarah Azhar, Hafiz Syed Imran-ul haque, Ambreen Qamar

Journal of Pharmaceutical Research International, Page 114-119
DOI: 10.9734/jpri/2020/v32i3530983

Socioeconomic status and the education of mother plays important role in providing better health care and nutrition to children. To the best of our knowledge the major population of Pakistan belongs to middle class and identification of malnutrition in our setups may help the policy makers to develop certain parameters to provide better nutrition to children under 5 years of age. The aims of current study were to analyze the prevalence of malnutrition and their association with different socioeconomic status in tertiary care hospital of Hyderabad.

Study Design: Cross sectional.

Place and Duration of Study: Study was performed at nutritional stabilization center of pediatric department of tertiary care hospital Hyderabad during the month of July 2019 to January 2020.

Methodology: Preformed proforma was designed to record the data of participants. Hospital protocols using WHO guidelines (17) i.e. 10 steps for in-patient care of severe malnutrition were started & followed with feeding F-75 & F-100. Data was analyzed on SPSS-20.

Results: The minimum age recorded was 8 months and maximum was found to be 45 months (3 years 9 months). 72% were females and 70% of participants had Weight to height ratio below normal. Prevalence of severe acute malnutrition was found to be 35.2%. After admission and management protocols 91.6% were recovered however, mortality was observed in 8.9% participants. Chi square analysis of all socioeconomic groups showed highly significant results with severe acute malnutrition (p-value= 0.001).

Conclusion: Current study concluded a high prevalence of SAM in Pakistani population that is about 35.2%, out of which majority was from lower socioeconomic class.

Open Access Original Research Article

Japanese Encephalitis Knowledge among University Students

Muhammad Shahid Iqbal, Salah-Ud-Din Khan, Muhammad Zahid Iqbal

Journal of Pharmaceutical Research International, Page 120-128
DOI: 10.9734/jpri/2020/v32i3530990

Objective: The objective of the study was to evaluate the knowledge of future healthcare providers about Japanese Encephalitis in a university in Malaysia.

Methods: A cross-sectional study was conducted among the students of three different healthcare provider faculties in a university in Malaysia with the help of pre-validated research questionnaire. The Statistical Package for Social Science (SPSS) Version 24.0 was utilized to analyze and present the data.

Results: Overall, 252 respondents from three different health care faculties participated in the current study. The medical faculty students had better knowledge as compared   to the other two faculties. The students living in their houses with their families had  better knowledge about Japanese Encephalitis as compared to the students who were living in hostels.

Conclusion: Overall appropriate knowledge was observed among the three health care provider faculty students. The present study concluded that medical students had more adequate knowledge of Japanese Encephalitis than the other two faculty students.

Open Access Review Article

Mechanisms of Diabetic Neuropathies and Antioxidant Therapy

Mujahid A. Alsulaimani, Rania M. Magadmi, Ahmed Esmat

Journal of Pharmaceutical Research International, Page 28-43
DOI: 10.9734/jpri/2020/v32i3530977

Background: Diabetic neuropathy is very common and affects half of patients with either type 1 or type 2 diabetes mellitus. It is the leading cause of diabetes-related hospital admissions and nontraumatic amputations. Currently, the keys to management are maintaining blood glucose concentration within the normal range and treatment of symptoms. Despite many studies of chronic pain associated with diabetic neuropathy, few improvements have been made.

Main Finding: This is a review of the classification of diabetic neuropathy, molecular mechanisms, and treatment options focusing on antioxidants.

Conclusion: As oxidative stress may play a significant role in the pathophysiology of diabetic neuropathy, the study of molecular mechanisms by which hyperglycemia induces oxidative stress is important. New targets for disease-modifying drugs could be elucidated.

Open Access Review Article

Selective Glucocorticoid Receptor Modulator: A Novel Class of Anti-inflammatory Compounds

Mujahid A. Alsulaimani, Mahmoud Alsulaimani

Journal of Pharmaceutical Research International, Page 55-66
DOI: 10.9734/jpri/2020/v32i3530979

Background: Glucocorticoids exert a wide range of physiological effects. They  effectively control various inflammatory and autoimmune diseases and play an important role in organ transplantation. Glucocorticoids are associated with unfavorable side effects that restrict their utilization. The most undesirable side effects are related to the transactivation of target genes. On the other hand, the transrepression of the genes is also responsible for the anti-inflammatory and immunomodulator of glucocorticoids.

Principal Findings: The separation between these two processes through alteration in glucocorticoid receptor resulting in a compound with similar GCs benefit activity with fewer side effects. This review will discuss the molecular mechanism and summarizes the most common compounds and their beneficial effect in preclinical experiments.

Conclusion: Several compounds that possess this feature are tested in preclinical experiments with promising results. These compounds are expected to be a better alternative to GCs drugs in the management of different diseases with a high degree of effectiveness.

Open Access Review Article

The Association of Vitamin D with Brain Cognitive Functions: A Literature Review

Yahya A. Alzahrani, Mohammed A. Alomary, Abdulmajeed A. Alzahrani, Mawaddah M. Eskandarani, Iman S. Aljabry, Yahya M. Alzahrani

Journal of Pharmaceutical Research International, Page 97-113
DOI: 10.9734/jpri/2020/v32i3530982

Vitamin D is a well-known steroid hormone that plays an important role in controlling bone levels of calcium, phosphorus, and overall mineralization. Several animal and human studies indicate that vitamin D hypovitaminosis may be linked to an increased risk of developing Alzheimer's disease and dementia. The objective of the present review is to summarize current knowledge of the effects of vitamin D deficiency and vitamin D intake on cognitive function. The possible underline mechanisms of these effects were also discussed. We reviewed the literature starting from 1986 to 2019 by searching PubMed, Cochrane, Semantic Scholar, Medline, Scopus, and Cochrane Library databases for all observational studies, randomized clinical trials, meta-analyses, and systematic reviews using the keywords  “vitamin D and Alzheimer disease”, “neuroprotective effect of vitamin D”, “vitamin D deficiency and Alzheimer ”, “role of vitamin D in neurodegenerative diseases ”, ” vitamin D and amyloidogenesis”, “acetylcholine and vitamin D”, and “memory and vitamin D ”.We also referred to animal and in vitro studies that dealt with the possible mechanisms of actions of the neuroprotective effect of vitamin D. Our findings showed that Vitamin D supplementation improves cognitive performance via reducing amyloidogenesis, restoration of neurotransmission, maintaining calcium balance, regulating neurotrophic factors, anti-inflammatory action, apoptosis regulation, antioxidant, and vascular processes. This review might be open new horizons in the understanding of the molecular mechanisms of the disease and neurodegeneration and enable the development of new approaches in treatment and prevention of the disease.