Open Access Short Research Article

Cytotoxicity of Endocytosis and Efflux Inhibitors in the BeWo Cell Line

Mansi Shah, Luke Bourner, Shariq Ali, Sanaalarab Al-Enazy, Erik Rytting

Journal of Pharmaceutical Research International, Page 1-7
DOI: 10.9734/JPRI/2017/34606

Aims: The purpose of this study was to determine the cell viability and cytotoxicity of various endocytosis and efflux inhibitors which can be used to determine transport and uptake mechanisms in the BeWo (b30 clone) human placental trophoblast cell line. Ethanol and dimethylsulfoxide (DMSO) were also studied since they are often used as cosolvents for administration of these inhibitors.

Methodology: The water-soluble tetrazolium-1 (WST-1) assay was used to quantify cell viability and the lactate dehydrogenase (LDH) assay was used to determine cytotoxicity.

Results: By the WST-1 assay, reduced cell viability was observed following 4 hours of exposure to chlorpromazine (10 µg/mL), colchicine (1 mM), filipin (3 µg/mL), gentamicin (2 mM), GF120918 (1 µM), methyl-β-cyclodextrin (5 mM), and verapamil (100 µM). By the LDH assay, however, no cytotoxicity was observed after 4 hours of exposure to the aforementioned compounds.  Amiloride (500 µM), ethanol (up to 0.1% v/v), and DMSO (up to 0.1% v/v) did not reduce cell viability nor induce cytotoxicity. 

Conclusion: This information is valuable when selecting potential inhibitors of endocytosis and efflux and the selection of time points for mechanistic studies.

Open Access Short Communication

Development and Validation of New Analytical Method for the Determination of Particle Size Distribution of Metformin Hydrochloride Using Laser Based Particle Size Analyzer

Amit Gosar, Shivaji Folane, Sanjay Pawar, Mithun Gharat, Amit Lalge, Shivaji Jadhav

Journal of Pharmaceutical Research International, Page 1-9
DOI: 10.9734/JPRI/2017/33911

Metformin Hydrochloride has characteristic nature of lump formation and determination of particle size with reproducible result is difficult and particle size determination method is not reported in literature. Hence novel rugged and reproducible method has been developed for the determination of particle size distribution of Metformin Hydrochloride.The wet method using Isopar G as dispersant has been developed and validated as per International conference on Harmonization guidelines (Q2R1) and found out robust and reproducible with % RSD of d(10), d(50) and d(90) values found within acceptance limit ranges from 6.05% to 21.84%  for d(0.1), 3.04% to 9.87% for d(0.5) and 4.69% to 14.32% for d(0.9) in validation.

The described method is accurate and validated and successfully applied for the determination of particle size distribution of Metformin Hydrochloride.

Open Access Original Research Article

A Model to Determine Effective Factors on Pharmacy Major Selection (A Case Study: Students of Zabol University of Medical Sciences)

Mahdi Eydi, Zahra Moradi, Reza Randian, Ali Rahdari, Amin Aliabadi

Journal of Pharmaceutical Research International, Page 1-8
DOI: 10.9734/JPRI/2017/31530

Background: Annually, a large number of students tend to study pharmacy. Students enthusiastically begin their studies; however, they lose their tendency over time. This study addresses motives and effective factors on pharmacy major selection as well as factors which discourage students in continuing their field of study.

Materials and Methods: This was a descriptive-analytic study which recruited 120 pharmacy students of Zabol University of Medical Sciences randomly and period of this study was four months. This study was conducted in 2016 on 120 students in Zabol University of Medical Sciences and all the students with Personal satisfaction take part in this choose. Participants included 71 female and 49 male students; moreover, 107 students were single and 13 students were married. These students were native (66.7%) or non-native (33.3%).

Results: Data was collected by questionnaire measuring demographic variables and effective factors on major selection. The questionnaire was developed on a Likert scale. Subjects were asked to fill the questionnaire. The collected data was analyzed by using an independent t-test, Chi-square test and other relevant tests. Analysis of data showed a significant relationship between Pharm.D degree, social status and suitable income (P<0.05); these factors are the most important factors effective on pharmacy major selection. Moreover, the results showed that good career prospect was the most important factor in discouraging students to continue their major. This study found no significant relationship between native students (those born in the city of education) and discouragement. Moreover, Chi-square test showed no significant relationship between gender, marital status, parental education and maternal education and encouragement or discouragement (P>0.05). So As found by the relevant questionnaire, the most important factor which motivates students is good job prospect.

Discussion and Conclusion: according to findings, most students were satisfied with their major. People who selected pharmacy based on their personal interest still believed that they would achieve their predetermined goals. Thus, lack of attention to this problem will influence pharmacy profession in the near future.

Open Access Original Research Article

Efficacy and Safety of Reimbursed Orphan Medicines in Bulgaria – Systematic Review and Meta-analysis (Part I)

Maria Kamusheva, Konstantin Mitov, Miglena Doneva, Assena Stoimenova, Maria Dimitrova, Guenka Petrova

Journal of Pharmaceutical Research International, Page 1-14
DOI: 10.9734/JPRI/2017/34031

Background: To make reimbursement decisions for orphan medicines the regulators need robust evidences for their efficacy and safety provided by systematic reviews and meta-analyses.

The goal of the current study is to evaluate the efficacy and safety of orphan medicines included in the Positive Drug List (PDL) in Bulgaria through the application of meta-analysis.

Methods: Internet based literature search in scientific databases such as Pub Med, ClinicalTrials.gov, EU Clinical Trials Register for the identification of all published clinical trials with orphan medicines Idursulfase, Sapropterin and Pasireotide was performed. The technological Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram was applied to present the flow of information during the different stages of systematic review. A set of statistical methods available in statistical software MedCalc were used to perform meta-analysis and comparison of proportions for diseases’ specific clinical parameters and adverse reactions. The studies were filtered on the basis of eligibility criteria: A clinical focus; randomized or open-label studies with clearly presented outcome variables; equal or similar time horizon; sufficient data about safety and efficacy processed with reliable statistical approaches.

Results: Fixed effect was used in patients treated with Idursulfase who experienced urticaria (p = 0.3459, 6.81%, 95% CI 3,126-12,623) and serious adverse drug reactions (ADRs) (p=0.0619, 21.27%, 95% CI, 14,561 - 29,345) and in patients treated with Sapropterin who experienced ADRs (P = 0.2264, 29,237%, 95% CI 20,916-38,720). Random effect was taken into account for Pasireotide effectiveness data and the percent of patients with controlled levels of urinary free cortisol (UFC) was 44.81%, 95% CI (37,506 - 56,073), which proves the difference in the effects among different samples. The results from the heterogeneity test shows that random effect for the percent of Pasireotide treated patients with nausea (р=0,2675, 51,936%, 95% CI 40.401-63,32), hyperglycemia (p=0,0504, 43.268%, 95% CI 34.217-52.662) and diarrhea (p=0.3221,58,299%, 95% CI 46.658-69.299) must be applied.

Conclusions: The aggregated data on efficacy presented by meta-analysis could be used for the conduction of pharmacoeconomic analysis for the purposes of the assessment of orphan medicines efficiency.

Open Access Original Research Article

Performance Optimization of Sustained Release Arginine Alginate Microbeads with a Natural Polysaccharide

Ritesh Kumar Tiwari, Lalit Singh, Vijay Sharma

Journal of Pharmaceutical Research International, Page 1-11
DOI: 10.9734/JPRI/2017/34305

Objectives: The design of effective and safe novel drug delivery systems has become an integral part for the development and formulating of new medicines. So, research continuously keeps on searching for new ways to deliver drugs over a long period of time or for a well-controlled release profile, to minimizing the loss of drug, to reduce the side effect. The objective of this study was to develop suitable microbeads of L-arginine for sustained release delivery by varying the alginate concentrations, starch concentrations using analytical and statistical approaches.
Materials and Methods: The work investigates the development and optimization of novel microbeads of potato starch-alginate blend containing L-arginine by ionotropic gelation using response surface methodology. Response surface methodology was found to be satisfactory for describing the relationships between formulation set variables and response variables. The influence of various formulation factors such as In vitro drug release, entrapment efficiency, SEM, analysis, swelling study and micromeritic properties, was investigated. These were also characterized by SEM, analysis.
Results: L-arginie containing microbeads were in the size range of 0.175 ± 0.02 to 0.226 ± 0.02 mm. The drug entrapment efficiencies were found in the range of 42.5 ± 1.83% to 91.2 ± 1.05% and the drug release were found at 10 h in the range 84.568 ± 2.75% to 99.761 ± 1.99%. The release pattern observed was a biphasic, characterized by an initial burst effect followed by slow release. No significant change was found during stability studies of optimized formulation at different temperature and humidity conditions as per ICH guidelines.
Conclusion: The data suggest that sweet potato flour is a potentially useful natural material for making sustained release L-arginine loaded microbeads by the ionotropic gelation technique.