Open Access Original Research Article

Investigate the Effect of Fatty Acids on Rheological Properties and In vitro Permeability of Escitalopram Oxalate from Hydroxypropyl Cellulose Gel Formulations

Nisarg Modi, Marina Borovinskaya, Fotios Plakogiannis, Rutesh Dave

Journal of Pharmaceutical Research International, Page 1-10
DOI: 10.9734/JPRI/2017/37901

The present studies evaluate rheological properties and in-vitro permeability properties of Escitalopram Oxalate (ECO) containing hydroxypropyl cellulose (Klucel HF, HPC) gels prepared with different carbon chain length containing fatty acids. The formulations were prepared by mixing solvent, escitalopram oxalate and kulcel HF (HPC) in homogenizer at 25000 RPM. A controlled stress rheometer was used to study the effect of different number of carbon chain fatty acids on the rheological properties and microstructure of HPC gels. The in-vitro permeability study was performed using human cadaver skin in order to evaluate the enhancing effect of fatty acids. The studies demonstrated that as the carbon chain length increased (C10-C18) the zero-shear viscosity, and yield stress value increased, which suggested that the stability of gel structure was increased with increase in carbon chain of fatty acids. Cohesive Energy was also depended on the carbon chain of fatty acids. There was decreased in cohesive energy as decrease in carbon chain of fatty acids. Temperature loop was created using heating and cooling temperature cycle. Oleic acid (C18) gave the best thermal stability with lowest temperature loop area. Increase in carbon chain length of fatty acids decreased the permeability enhancing effect of Escitalopram Oxalate through human cadaver skin during In-vitro permeability studies. The permeability of ECO through human cadaver skin was found to be in increasing order as capric acid> lauirc acid> Oleic acid> No-enhancer. Rheological studies could be useful to investigate the internal structure of HPC gels. Fatty acids alter the rheological properties of HPC gels such as zero shear viscosity, yield stress and cohesive energy. Moreover, In-vitro permeability results demonstrated that HPC gels containing fatty acids could be potential delivery system for transdermal delivery of ECO.

Open Access Original Research Article

Design and Evaluation of a New Fixed-Dose Immediate Release Capsule of Atenolol, Enalapril Maleate and Hydrochlorothiazide

Nickania A. Pryce, Amusa S. Adebayo, Deon A. Bennett, Eugenie Brown-Myrie

Journal of Pharmaceutical Research International, Page 1-16
DOI: 10.9734/JPRI/2017/38019

Aim and Objectives: To design, formulate and perform in vitro studies of a fixed dose combination (FDC) immediate release solid dosage form of the antihypertensive drugs atenolol, enalapril and hydrochlorothiazide. The objectives of the study were to perform pre-formulation studies, design an immediate-release FDC capsule dosage form, and evaluate the prepared dosage form.

Methods: Differential Scanning Calorimetric (DSC) analysis of physical mixtures of drugs and drug-excipient combinations was used to assess compatibility. Binary mixtures of atenolol and enalapril form a eutectic mixture indicating that a tablet dosage form, in which the drugs would be highly compressed together, may not be stable. Hard gelatin shell encapsulation was therefore employed. Atenolol and enalapril were separately dry-granulated with hydrochlorothiazide and excipients and mixed together at appropriate therapeutic proportions and encapsulated in size 1 hard gelatin capsules (HGC). Preliminary screening produced five formulations each with similar proportions of the 3-drug FDC but with 5 different levels of disintegrant. Capsule weight variation, disintegration time and dissolution rate were determined as output variables, following USP procedures. For the dissolution studies, a reverse phase high-pressure liquid chromatographic (RP-HPLC) method was developed for simultaneous analysis of the three drugs.

Results: Granules possessed good fluidity (compressibility index 8.53 to 11.63 and tapped bulk density 1.09 to 1.132). Capsule disintegration time was generally £ 2 minutes while 80% of each drug dissolved within 20 minutes. Capsules showed no sign of physical instability or adverse effect during a period of 1 year shelf storage at room temperature (average temperature 25°C).

Conclusions: Granules possess adequate fluidity and compressibility for filling into HGC. Results generally indicated that an immediate release FDC capsule of atenolol, enalapril and hydrochlorothiazide was stable for more than 1 year of observation. Capsule disintegration time and dissolution rate were generally within the USP specification.

Open Access Original Research Article

Antibacterial Activity of Ocimum gratissimum L. against Some Selected Human Bacterial Pathogens

Ajose Daniel Jesuwenu, Okozi Ogheneoremume Michael

Journal of Pharmaceutical Research International, Page 1-8
DOI: 10.9734/JPRI/2017/37897

Aim: This study was designed to investigate the bioactive spice to determine its activity against some selected human bacterial pathogens. The spice studied was Ocimum gratissimum (clove basil).

Place and Duration of study: Microbiology laboratory of Bells University of Technology between October, 2016 to July, 2017.

Methodology: The plant extracts was tested for their activity against Staphylococcus species, Escherichia coli, Enterococcus faecalis, Proteus mirabilis and Klebsiella pneumoniae collected from microorganism bank of Bells University of Technology. Antibacterial activity was carried out using agar diffusion method while agar dilution method was employed for determining the minimum inhibitory concentration (MIC) on Mueller-Hinton agar.  

Results: The findings of this study showed that the spice contained phytochemicals which made it active against the tested microorganisms. Hot water extract was more active against all tested isolates with MIC of 5.0 mg/ml against Klebsiella pneumoniae to 10 mg/ml against Escherichia coli, Proteus mirabilis, Staphylococcus aureus and Enterococcus faecalis. Zone of inhibition was between 18 mm for Staphylococcus aureus and Enterococcus faecalis and 31 mm for Proteus mirabilis.

Conclusion: Ocimum gratissimum has a broad spectrum antibacterial activity against all tested isolates and thus has a potential as a source of natural drugs. However, in vivo studies are recommended.

Open Access Original Research Article

QSAR Pharmacophore-based Virtual Screening, CoMFA and CoMSIA Modeling and Molecular Docking towards Identifying Lead Compounds for Breast Cancer Protease Inhibitors

Lan Huang, Xuan R. Zhang, Pei H. Luo, Lun Yuan, Xang Z. Zhou, X. Gao, Ling S. Li

Journal of Pharmaceutical Research International, Page 1-10
DOI: 10.9734/JPRI/2017/37821

Aim: This study used QSAR Pharmacophore-based virtual screening and molecular docking to identify lead compounds and determine structural requirements for breast cancer inhibitor development. CoMFA and CoMSIA modeling was employed to design more potential inhibitors.

Materials and Methods: 3D-QSAR pharmacophore models were developed using HypoGen Module and validated by Fischer’s model and decoy test. The best pharmacophore model was employed to screen ZINC chemical library to obtain reasonable hits. Following ADMET filtering, 18 hits were subjected to further filter through docking. CoMFA and CoMSIA models were built by partial least squares on phenylindole-3-carbaldehydes derivatives.

Results: 19 random runs from Fischer’s validation and decoy test which led to an enrichment factor of 48.23 and Guner-Henry factor of 0.774 show that the identified pharmacophore model is highly predictive. Top three hits (IC50=0.01~0.05 µM, fitness =52~62) were identified as potential inhibitory candidates from virtual screening and docking, and three new lead compounds were designed with predicted inhibiting potencies by pIC50 value of 8.55 from CoMFA and CoMSIA modeling and fitness value of ~59 from docking.

Conclusion: Validation results and decoy test indicate that the developed pharmacophore model is highly predictive. Residue Sep6 and Cys 5 were observed as important active sites for ligand-protein binding. Top three hits were identified as more potential inhibitors, and the designed compounds show more inhibiting potencies. The QSAR and docking results obtained from this work should be useful in determining structural requirements for inhibitor development as well as in designing more potential inhibitors.

Open Access Original Research Article

Antifungal, Antioxidant and Phytochemical Screening of Melia azedarach Flower Extracts by Using Different Solvents

Muhammad Khawar Abbas, Mahmood Ahmad, Kashif Barkat, Naila Aslam

Journal of Pharmaceutical Research International, Page 1-12
DOI: 10.9734/JPRI/2017/38246

Objective: To investigate the antifungal, antioxidant and phytochemical screening of Melia azedarach flowers by using different solvents.

Materials and Methods: Antifungal activity was experimented against three fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus). Antifungal activity of extract was measured by using agar well diffusion and serial microdilution methods. Antioxidant activity has been measured by 2, 2-diphenyl-1-picryl-hydrezyl [DPPH] free radical scavenging assay. Phytochemical screening was done by doing different tests for presence of saponins, anthraquninone glycosides, cardioactive glycosides, phenolic glycosides, cynogenic glycosides, phenols, alkaloids, tannins and flavonoids.

Results: Methanolic extract of Melia azedarach flowers showed highest antifungal activity against Aspergillus flavus fungus with zone of inhibition of 19.6±0.66 mm. Dichloromethane, ethyl acetate and n-butanol extracts showed significant antifungal activity with 18±0.57 mm, 18.6±0.88 mm and 18±0.66 mm zone of inhibition, respectively. N-butanol extract showed lower antifungal activity against Aspergillus niger with 13.6±0.88 mm zone of inhibition. Dichloromethane and methanolic extracts exhibited excellent minimum inhibitory concentration against Aspergillus flavus (13.909±1.5 µg/ml). Antioxidant activity has been measured by DPPH free radical scavenging assay. Only ethanolic extract of Melia azedarach flowers showed antioxidant activity with value of IC50 = 50±2.0. While dichloromethane, ethyl acetate, n-butanol and methanol showed no antioxidant activity. Phytochemical screening showed presence of saponins, anthraquninone glycosides, cardiaoactive glycosides, phenolic glycosides, cynogenic glycosides, phenols, alkaloids, tannins and flavonoids.

Conclusion: These findings demonstrate that leaf extracts of Melia azedarach extracts possess excellent antifungal activity and have potential to reduce problems of fungal pathogens.