Open Access Original Research Article

Characteristics, Complexation and Analytical Methods of Darunavir

Ana Carolina Kogawa, Hérida Regina Nunes Salgado

Journal of Pharmaceutical Research International, Page 1276-1286
DOI: 10.9734/BJPR/2014/7607

What is it? Darunavir is a protease inhibitor used in the treatment of HIV infection. It is an important drug of therapy cocktail for patients infected with the virus. On the market there are darunavir ethanolate tablets of 75, 150, 300, 400, 600 and 800mg, because this is the most stable form. It is commercialized by Janssen-Cilag with the name PrezistaTM.
Why we started? This drug has low water solubility and poor bioavailability, therefore requires administration in doses relatively high to the success of the therapeutic effect. The complexation of drugs by using cyclodextrin is welcome in this respect to improve the solubility and hence increase the dissolution rate of poorly soluble drugs. A monograph about this compound has not been described, thus it is an extremely important quality control of darunavir to demonstrate its effectiveness and safety.
What we did? Some existing analytical techniques have been discussed in this manuscript, focusing on bioanalytical and pharmaceutical quality control applications.
What we found? This review showed the published analytical methods reported for the determination of darunavir and discuss about its characteristics and complexation with cyclodextrin.

Open Access Original Research Article

Analysis of Fenoterol and Ipratropium Transfer from Human Lung Tissue into Human Plasma Using a Dynamic Dialysis Model

Beatrice Trammer, Boris Kardziev, Michael Schmidt, Petra Högger

Journal of Pharmaceutical Research International, Page 1287-1299
DOI: 10.9734/BJPR/2014/9993

Aims: The aim of the current study was to establish a simple and yet as much as possible physiologic approach for a simulation of the pulmonary absorption process to compare different inhaled drugs or drug formulations.
Methodology: We designed a dialysis setting that allowed monitoring the drug release from human lung tissue into a continuous-flow plasma compartment. For proof-of-concept experiments we chose the glucocorticoid fluticasone propionate (FP) as model compound. For subsequent experiments we selected a commercially available metered dose inhaler delivering a fixed combination of the short-acting ß2-agonist fenoterol and the muscarinic antagonist ipratropium bromide.
Results: With the novel dynamic dialysis model we observed high drug transport rates from the lung tissue into plasma including an elimination phase. The concentration profile in the plasma compartment of our model system was similar to the plasma concentration courses after inhalation of FP. Compared to FP significantly higher drug fractions of fenoterol and ipratropium bromide were released into plasma and the transfer of ipratropium was more pronounced compared to fenoterol. Again, concentration profiles in plasma were alike to those described in clinical studies.
Conclusion: We suggest that this model is appropriate for rapid assessment of comparative diffusion behaviour of drugs or drug formulations from lung tissue into plasma.

Open Access Original Research Article

Anti Diabetic activity of Terminalia superba (Combretaceae) Stem Bark Extract in Streptozotocin Induced Diabetic Rats

Dzeufiet Djomeni Paul Désiré, Nguelefack Télesphore Benoît, Azay Jacqueline, Cros Gérard, Kamtchouing Pierre, Dimo Théophile

Journal of Pharmaceutical Research International, Page 1300-1310
DOI: 10.9734/BJPR/2014/9163

Aims: The present study was designed to evaluate the antidiabetic activity of the methanol stem bark extract of Terminalia superb (T. superba), a traditionally used medicinal plant in Cameroon.
Place and Duration of Study: Departement of Animal Biology and Physiology, Faculty of Science, University of Yaounde I, Cameroon and Laboratoire de Pharmacologie et Physiopathologie Expérimentales, Université Montpellier I, France. Between Ferbruary 2011 and September 2011.
Methodology: In one set of experiments, repeated doses of T. superba extract (37.5– 300mg/kg, p.o.) were administrated once daily for 21 days to groups of diabetic rats. In another set of experiments, acute effect of the plant extract (37.5–300mg/kg) in diabetic rats was evaluated.
Results: Following acute treatment, the plant extract produced a significant reduction in the blood glucose levels in diabetic rats. T. superba (75–300mg/kg) significantly decreased the blood glucose levels in glucose loaded rats. Oral administration of T. superba extract for 21 days resulted in a 31.43% and 21.42% significant reduction in blood glucose levels at the dose of 75mg/kg and 300mg/kg respectively. The plant extract significantly, reduced the plasma urea levels (20%) and induced a significant elevation in plasma insulin in treated rats. The extract did not significantly change elevated plasma cholesterol and triglycerides resulting from diabetic conditions.
Conclusion: The antidiabetic effect of the methanol stem bark extract of T. superba seems to be a result of increase in glucose utilization due to stimulatory action on insulin release.

Open Access Original Research Article

UPLC-MS/MS Determination of Aceclofenac and Diclofenac in Bulk, Dosage forms and in At-line Monitoring of Aceclofenac Synthesis

Ramzia I. El-Bagary, Hassan M. E. Azzazy, Ehab F. ElKady, Faten Farouk

Journal of Pharmaceutical Research International, Page 1311-1331
DOI: 10.9734/BJPR/2014/5676

Aim: The derivatization product of diclofenac (DCL), aceclofenac (ACL), is a non-steroidal anti-inflammatory drug (NSAID) which causes faster and extended action with reduced gastrointestinal (GI) inflammation. The detection of DCL in ACL bulk and pharmaceutical products indicates incomplete synthesis and hydrolysis.
In this article we have developed a UPLC-MS/MS method for analysis of ACL and DCL. The method was designed as an at-line monitoring tool for process analytical technology (PAT) application to ACL synthesis. The method was also applied for analysis of ACL and DCL in bulk and tablets.
Methodology: Isocratic elution was performed on a UPLC C18 column (2.1 x 50 mm, 1.7 µm) using a mobile phase consisting of acetonitrile, water and formic acid (80:20:0.5, v/v/v). Flow rate was 0.2 mL/min and total run time was 1 min. Auto-sampler temperature was maintained at 5ºC to prevent any further degradation of ACL. Electrospray positive ionization (ESI +Ve) in multiple-reaction monitoring mode (MRM) was used for the simultaneous determination of ACL and DCL. Monitoring was performed at [M+H]+ 354.23: 250.09 and 296.13:250.1 m/z; respectively. The method was validated according to ICH guidelines Q2(R1).
Results: The linearity range was 20 – 3000 ng/mL for both drugs. The developed method was accurate and precise (RSD<2%) for the determination of ACL and DCL in single solution (99.65±1.33 and 100.37±1.02 for ACL and DCL; respectively) and laboratory prepared mixtures (101.01±1.07 and 100.45±1.54 for ACL and DCL; respectively). The method was applied to Bristaflam® and Cataflam® tablets and the recovery was 100.95±0.18 and 99.15±0.62; respectively. The average recovery from reaction mixture was101.21±0.06 and 98.89±0.64 for ACL and DCL; respectively.
Conclusion: The proposed UPLC-MS/MS method is valid for at-line monitoring of ACL and DCL during PAT application to ACL synthesis and drug determination in bulk and tablets.

Open Access Original Research Article

Perception of Pharmaceutical Care Roles of Pharmacists among In-patients in a Tertiary Care Facility in Jos City, Nigeria

S. J. Igbanugo, I. S. Dabi, I. O. Abah

Journal of Pharmaceutical Research International, Page 1332-1340
DOI: 10.9734/BJPR/2014/10222

Aims: The study is aimed at gaining a better understanding of the perception of in-patients on the pharmaceutical care (PC) roles of pharmacists. This is useful in assessing the quality of care provided by the pharmacist and in the design and implementation of improved PC program in Nigeria.
Study Design: A cross-sectional, descriptive study.
Place and Duration of Study: Jos University teaching hospital (JUTH), between June and October 2013.
Methodology: The perception of the PC roles of pharmacists was assessed in consented in-patients, using 23-items self administered questionnaire. Factors of PC assessed included: knowledge of the pharmacy profession, interpersonal relationship, collaboration with other professionals, and managing therapy. Factors associated with the perception of respondents on the PC roles of pharmacists were analyzed using Chi-square and Mann-Whitney U Test.
Results: A total of 548 out of 551 questionnaires were completely filled and analyzed (response rate 99%). Majority (64%) of the respondents are in the age range of 21-40 years. Females accounted for 53% (n= 288). Overall, perception of respondents was excellent with a mean percentage perception score of 86% [95% confidence interval: 84 to 88%]. Knowledge of the pharmacy profession had the highest positive perception score of 89% while Interpersonal relationship had the highest negative perception score of 16%. Sex, marital status and ward of admission were significantly associated with respondents’ perception, whereas age and occupation were not.
Conclusion: In general, in-patients in JUTH have excellent perception about the PC role of the pharmacist. However, there is a need to develop strategies to improve on the therapeutic relationship which is critical to the attainment of PC goals.

Open Access Original Research Article

Synthesis of Silver Nanoparticles and Incorporation with Certain Antibiotic Using Gamma Irradiation

A. I. El-Batal, Bakry M. Haroun, Ayman A. Farrag, Ahmad Baraka, Gharieb S. El-Sayyad

Journal of Pharmaceutical Research International, Page 1341-1363
DOI: 10.9734/BJPR/2014/9566

Aims: The study was explaining that silver nanoparticles (AgNPs) were synthesized biologically by Bacillus megaterium culture supernatant (as reducing and stabilizing agents) by the optimization of medium components for nitrate reductase production to enhance the synthesis of AgNPs. And use of gamma irradiation for the synthesis and incorporation of AgNPs with selected antibiotics at distinct dose.
Place and Duration of Study: The study was carried out in 2012 in the Department of Drug Radiation Research, Egyptian Atomic Energy Authority.
Methodology: The optimized conditions for AgNPs formation by B. megaterium culture supernatant were as follows; media containing: (%) yeast extract: 0.15, peptone: 0.25, KNO3:0.1 temp: 30ºC and incubation period 24 h with maximum nitrate reductase activity of (680.89U/ml). Physical synthesis of AgNPs and incorporation with antibiotics such as (Sodium Cefotaxime, Gentamycin sulphate and Amoxicillin) by γ-rays doses such as (0.5, 1, 1.5, 2, 2.5 and 3 kGy) were studded. AgNPs were characterized by (UV-Vis.), (DLS), (FT-IR) and (TEM) analysis. Combined and individual antibacterial activities of Amoxicillin and AgNPs were investigated against different pathogenic bacterial species by measuring the (ZOI) and by determining the (MIC).
Results: This method shows that Aqueous Ag+ ions were reduced to AgNPs when added to the cell-free supernatant of B. megaterium this is indicated by the color change from whitish yellow to brown and the control showed no color change. In physical method Amoxicillin was incorporated with AgNPs perfectly at 2.5kGy. The decreasing order of the average antibacterial activity against bacterial group was observed to be AgNPs > Amoxicillin > Amoxicillin + AgNPs.
Conclusion: The radiation-induced AgNPs synthesis is a simple, clean which involves radiolysis of aqueous solution that provides an efficient method to reduce metal ions. B. megaterium was found to be an effective biological tool for the extracellular biosynthesis of AgNPs. The bactericidal activity have proved that AgNPs in combination with amoxicillin kill bacteria at such low concentrations (units of ppm), which do not reveal acute toxic effects on human cell, in addition to overcoming resistance, and lowering cost when compared to conventional antibiotics.

Open Access Original Research Article

Synthesis of Selenium Nanoparticles by Bacillus laterosporus Using Gamma Radiation

A. I. El-Batal, Tamer M. Essam, Dalia A. El-Zahaby, Magdy A. Amin

Journal of Pharmaceutical Research International, Page 1364-1386
DOI: 10.9734/BJPR/2014/10412

Aim: This study shows the possible synthesis of Selenium Nanoparticles (SeNPs) in aerobic optimized conditions using Bacillus laterosporus (B. laterosporus) bacterial strain.
Methodology: B. laterosporus was used to reduce selenium ions (selenite anions) to SeNPs by fermentation in Luria-Bertani Enrichment (EM) medium. Optimization of fermentation conditions using two-level full factorial design was performed. SeNPs were further characterized by UV-Vis., DLS, TEM, FT-IR, EDX and XRD analysis. SeNPs synthesis by Gamma irradiated B. laterosporus cells at different radiation doses was reported. Evaluation the probability of B. laterosporus to synthesis SeNPs by fermentation in skimmed milk aerobically. A microtiterplate assay was used to evaluate the ability of SeNPs to inhibit the biofilm formation of Pseudomonas aeruginosa. Evaluating the antimicrobial activity of some antibiotic agents upon addition of SeNPs was performed.
Results: B. laterosporus reduced the soluble, toxic, colorless selenium ions to the insoluble, non-toxic, red elemental SeNPs. Statistical analysis showed that the results were normally distributed. Temperature, incubation period and pH were significant factors in the fermentation process, in which the maximum SeNPs produced (8.37µmole/ml) was at temperature 37ºC, incubation period 48hr, pH7. The Gamma radiation exposure dose 1.5kGy gave the maximum SeNPs produced (10.01 µmole/ml). A pink color appear in the fermented milk revealing the formation of SeNPs-enriched milk. SeNPs inhibit the biofilm formation of Pseudomonas aeruginosa with a percentage reduction of 99.7%. SeNPs increase the antibacterial activity of fucidic acid by 13.6% and 28.5% against Escherichia coli and Staphylococcus aureus respectively. But with Gentamycin sulphate, no change in the antibacterial activity.
Conclusion: SeNPs can be synthesized aerobically by the probiotic B. laterosporus bacterial strain. SeNPs can be incorporated in nutraceuticals and functional foods like milk also can be used to inhibit the bacterial biofilm formation and can be added to some antibacterial creams to enhance their antimicrobial activity.

Open Access Original Research Article

Phytochemical Testing and In vitro Antibacterial Activity of Bixa orellana (Annatto) Seed Extract

Modupeola Abayomi, Amusa S. Adebayo, Deon Bennett, Roy Porter, Janet Shelly Campbell, Garth Dawkin

Journal of Pharmaceutical Research International, Page 1387-1399
DOI: 10.9734/BJPR/2014/10925

Aim: The present study was designed to investigate the antibacterial activity of the seeds of Bixa orellana(Annatto, family Bixaceae) extracts.
Methods: Powdered seed material was extracted using either organic solvents or acid-base protocols and the crystals obtained were washed with deionized water, oven-dried for about 12 hours at 45ºC and stored inair-tight containers. The antimicrobial activity of the ethanolic, dimethyl sulphoxide and aqueous extract of B. orellana seed was tested In vitro against Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Bacillus subtilis using agar well diffusion method.
Results: The antibacterial activity of the seed extract was observed at low concentration (250µg/ml) in ethanolic and dimethyl sulphoxide solution while, in potassium hydroxide, antibacterial activity against Staphylococcus aureus and Bacillus subtilis was observed at 750µg/ml. The minimum inhibitory concentration (MIC) values range from75 to 750µg/ml while the minimum bactericidal concentration (MBC) values occurred between 75 and 1500µg/ml respectively against Staph. aureus and B. subtilis respectively.
Conclusion: Results of this study indicated that the seed extracts of Bixa orellana possess significant inhibitory and bactericidal activities against select resistant strains of gram-positive bacteria.

Open Access Original Research Article

Evaluation of Thrombolytic Effect of Seven Different Bangladeshi Plants

Mohammed Abdullah Jainul, Shofiul Azam, Amin Chowdhury, Mohammad Mamun Ur Rashid, Abdullah Al Mamun, Hasibul Quader Chowdhury

Journal of Pharmaceutical Research International, Page 1400-1406
DOI: 10.9734/BJPR/2014/6854

Aim: From time past till date, proper documentation of the use of medicinal plants are helpful in drug development and research. The objective of this study is to evaluate several plant extracts of Bangladesh for their thrombolytic activity.
Study Design: There are seven different plants from unlike families were studied in this primary research work. They were collected between August-September (2012) and the thrombolytic effect of their extractions was investigated. Streptokinase was used as standard to compare with and evaluate the significance of each result.
Result: Among all studied plants Gardenia coronaria showed most promising result of 49.61±0.866% of lysis, whereas streptokinase exhibited a lysis of 75.36±0.964%. The extracts of Hedychium thyrsiforme and Artocarpus chaplasha showed also promising activity with 48.39±1.813% and 43.69±0.906% of thrombolytic effect, respectively.
Conclusion: All the plants used in this study showed promising thrombolytic activity compared to standard. Proper phytochemical characterization and isolation of the constituent compounds responsible for this activity may be further investigated and could be a future source of lead thrombolytic compounds.

Open Access Original Research Article

Development and Validation of UV Spectrophotometric Method for the Estimation of Haloperidol

Mohd Yasir, U. V. S. Sara

Journal of Pharmaceutical Research International, Page 1407-1415
DOI: 10.9734/BJPR/2014/10153

Aims: The aim of the present work was to develop and validate a sensitive, simple, accurate, precise & cost effective UV spectrophotometric method for the estimation of haloperidol in prepared pharmaceutical formulations of solid lipid nanoparticles.
Methodology: The different analytical performance parameters such as linearity, range, precision, accuracy, limit of detection (LOD) and limit of quantification (LOQ) were determined according to International Conference on Harmonization (ICH) Q2 (R1) guidelines. The study was performed in phosphate buffer of pH 7.4.
Results: The peak (λmax) of haloperidol appeared at a wavelength of 247.5 nm in phosphate buffer (pH 7.4). Beer-Lambert’s law was obeyed in the concentration range of 2–20 μg/ml with correlation coefficient (R2) 0.9994.
Conclusion: The results of the study demonstrated that the developed procedure was accurate, precise and reproducible, while being simple, cheap and less time consuming.

Therefore, this method can be suitably applied for the estimation of haloperidol in prepared solid lipid nanoparticles.