Open Access Minireview Article

Medication Errors and Root Causes Analysis: Emerging Views and Practices in King Saud Medical City, Riyadh, Saudi Arabia

Dalal S. Al-Dosaari, Ibrahim A. Al-Zaagi, Sara O. Salem, Abdullah Mohammed Al-Bedah, Naseem Akhtar Qureshi

Journal of Pharmaceutical Research International, Page 1-18
DOI: 10.9734/BJPR/2016/28742

Background: Medication errors (MEs) are associated with significant morbidity and mortality, and huge cost worldwide. Medication errors are multifactorial and present in different forms with variable severity. Many tools are developed to analyze MEs for knowing the main etiological factor and preventing their occurrence.

Objective: This mini-review narratively describes the emerging views and practices concerning MEs and root cause analysis (RCA) in King Saud Medical City (KSMC) supported by relevant international literature.

Methods: Electronic searches of PubMed and Google Scholar using keywords were made to identify relevant articles published in English literature of the past 10 years. For illustrative purpose, three case scenarios of MEs with step-wise process of RCA were presented in this research.

Results: A number of programs, orientation sessions, policies and procedures, ME reporting system, guidelines and action plan were developed to identify and prevent MEs, and RCA of MEs was the most important assessment tool to recognize the main causes underlying MEs in KSMC.

Conclusion: Several programs, developed and implemented in KSMC over the past few years match with international evidence-based data, and RCA is an effective tool to detect, analyze and prevent MEs in this medical city. This mini-review calls for further research on MEs and root cause analysis in other hospitals of Saudi Arabia.

Open Access Original Research Article

Development and Validation of HPLC Method for Analysis of Impurities of Fosfluconazole in Pharmaceutical Products

Qiang Li, Juan Liu, Jie Chen, Yi Huang, Xiaohong Yuan, Liangchun Li

Journal of Pharmaceutical Research International, Page 1-9
DOI: 10.9734/BJPR/2016/28451

The contents of three related substances in fosfluconazole were determined by high performance liquid chromatography (HPLC). The limit of detection (LOD) of the impurity A (2-(2,4-difluorophenyl)-1,3-bis (1H-1,2,4-triazole-1-yl)-2-propan-2-ol), the impurity B (2-(2,4-Difluorophenyl) -1-(1H-1,2,4-triazol-1-yl) -3-(4H-1,2,4- triazol-4-yl) propan-2-yl dihydrogen phosphate) and the impurity C (2-(2-fluorophenyl) -1,3-bis (1H-1,2,4-triazole -1-yl)-2-propyl dihydrogen phosphate) were 3.0, 3.0 and 5.0 μg/mL respectively. Limit of quantification (LOQ) were 10.0, 22.0 and 21.3 μg/mL for A, B and C. The method can be used for the quality control of the related substances in fluconazole injection, tablet and capsule.

Open Access Original Research Article

Fabrication of Lipid-Coated Chitosan Nanoparticles

Sheryhan F. Gad, Gihan N. Fetih, Sozan S. Tous, Giovanni M. Pauletti

Journal of Pharmaceutical Research International, Page 1-8
DOI: 10.9734/BJPR/2016/28714

Aims: Conventional chitosan nanoparticles (CSNPs) exhibit high encapsulation efficiency for hydrophilic drugs but lack substantial payload capacity for lipophilic drugs. This study explores fabrication of a novel lipid/chitosan nanocomposite suitable for combination therapy using hydrophilic and lipophilic drugs.

Methodology: Lipid coating of prefabricated CSNPs that were prepared by ionotropic gelation with tripolyphosphate (TPP) was accomplished in 0.1 M acetate buffer, pH 5.3, using an equimolar mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and L-α-dipalmitoylphosphatidyl glycerol (DPPG) or DPPC only. Dynamic laser light scattering (DLS) was used to monitor particle size distribution and zeta potential.

Results: Rapid addition of TPP to chitosan (CS) solution prepared in acetate buffer at a final TPP/CS = 0.3:1 (g/g) reproducibly resulted in CSNPs with a mean hydrodynamic diameter of 82.8±1.7 nm and a zeta potential of +20.5±1.2 mV. Hydration of dried phospholipid films using this CSNP suspension progressively increased mean particle size of colloids up to 613.5±13 nm depending on lipid composition and lipid concentration applied. Zeta potential of DPPC/CS nanocomposites was significantly reduced to +8.7±0.1 mV, whereas surface charge of (DPPC/DPPG, 50:50)/CS nanocomposites remained unchanged between +18.8 and +21.6 mV, respectively.

Conclusion: Physicochemical assessment of lipid/CS nanocomposites prepared by thin film hydration suggests successful surface immobilization of zwitterionic DPPC on prefabricated CSNPs. The presence of this additional lipid layer surrounding the hydrophilic CS core is predicted to facilitate effective encapsulation of lipophilic drugs enabling combination therapy with hydrophilic and hydrophobic payloads using a single nanodelivery system.

Open Access Original Research Article

Development and Validation of Liquid Chromatography Method for the Determination and Quantification of Impurities in Imiquimod

Sayyed Hussain, Tabrez Shaikh, Mazhar Farooqui

Journal of Pharmaceutical Research International, Page 1-9
DOI: 10.9734/BJPR/2016/28020

New stability indicating reverse phase high performance liquid chromatography (HPLC) method is developed for the determination of Imiquimod and its impurities. Separation is achieved on a C18 column (Inertsil-ODS3 4.6 × 250 mm, 5  µm) using gradient elution mode with mobile phase-A having disodium hydrogen phosphate buffer (10 mM) with 0.1% v/v triethyl amine and pH adjusted to 6.0 with ortho-phosphoric acid while mobile phase-B consist of an equal mixture of methanol and acetonitrile. The flow rate was optimized to 1.2 mL/min and column oven temperature 30°C. Detection was carried out at wavelength 226 nm. This developed method is then validated as per International Council for Harmonisation (ICH) guideline and found out to be linear, accurate, specific, selective, precise, and robust. The drug is also subjected to forced degradation using stress conditions of acid-base hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found out only in harsh condition of oxidative degradation where degradation impurity is also predicted. All degradation products were well separated. Test solution was found to be stable for 24 hrs. The method can be successfully applied for the determination of Imiquimod and its impurities in routine and stability samples.

Open Access Original Research Article

Ethnobotanical Medicinal Plants Used as Chewing Sticks among the Kenyan Communities

Kemboi Douglas

Journal of Pharmaceutical Research International, Page 1-8
DOI: 10.9734/BJPR/2016/28833

Background: Dental infections are among the most pursued global oral health problems. They are caused by plaque forming bacteria such as Myces, Actinobacillus, Streptococcus and Candida species which reside in the oral cavity. Chewing sticks have remained a common and acceptable teeth cleaning agent in different parts of the world especially in developing countries despite the widespread use of tooth brushes and tooth pastes. These are secondary forest products used by many communities in Kenya. They are used to treat wide range of oral infections and some have been reported by the herbalist to possess pharmacological properties. Despite their wide usage, not much has been investigated about the species mentioned for their importance according to local communities.

Aim: In view of this, the purpose of this research was to undertake an ethnobotanical study and evaluation of phytochemicals of the locally used medicinal plants as chewing sticks among western communities in Kenya.

Place and Duration: Research was carried out at University of Kabianga from January to May 2016.

Methodology: Secondary literature search and structured interviews among local informants in 5 Counties, Western Kenya was used to collect data. They were requested to list the species used as chewing sticks and to rank them by priority. To evaluate the pharmacological importance, phytochemical screening was done on organic extracts (leaves and stems) of the three species listed as priority according to local perceptions.

Results: In our findings, fifteen plant species belonging to different families were documented. It was observed that plants used by the locals are carefully selected for properties such as hardness, or bitterness and certain species were more popular than others among the users. Some of these species had medicinal properties and were used for the treatment of malaria, stomach upsets, cough, diarrhea, dysentery, and tuberculosis. The oral health status of the users, especially the youths and the middle aged were suggestions of the possible dental recipe, contained in some of these plant species especially the frequently used. Phytochemical screening of the extracts from the three species ranked as priority revealed the presence of alkaloids, tannins, flavonoids, saponins, terpenoids and carotenoids. Therefore the extracts contains compounds (phytochemicals) that have been reported to have an effect on oral pathogens and other ailments and thus prevent tooth decay and gum diseases.

Conclusion: Thus, the study ascertains the value of medicinal plants used in the Western Kenya and Kenya as a whole, which could be of considerable interest to the development of new drugs and production of new antibiotic. Use of these plants as chewing sticks can also be commercialized and be a source of income for many poor Kenyans upon scientific validation of their toxicity.

Open Access Original Research Article

Quantitative Structure-activity Relationships (QSAR) and Docking Studies on Pyrimidine Derivatives for Antitubercular Activity against M. tuberculosis H37Rv

Kawkab Ali Hussain, Sadiq M. H. Ismael, Wisam A. Radhi

Journal of Pharmaceutical Research International, Page 1-11
DOI: 10.9734/BJPR/2016/27274

Aim: QSAR techniques and docking increase the probability of success and reduce time and coast in drug discovery process. The study presents QSAR investigation on 20 pyrimidine derivatives for antitubercular activity against M. tuberculosis.

Materials and Methods: The relationship analysis between compounds and physicochemical properties under study was done by two methods Multiple linear regression (MLR) and Step wise Selection of Terms (SW). The results show good models with six and five (SW) parameters linear equations. While the molecular docking simulation study of selected target Cytochrome P450 14alpha-sterol demethylases (CYP51) of M. tuberculosis H37Rv(1E9X) and ligands (active pyrimidine derivatives) as well as 4-Phenyl-1h-Imidazol for comparison was performed by using Autodock software.

Results: The best model predicted in this study was the eq. 1 (MLR) with excellent statistical fit as SE = 9.06234   R-Sq = 94.9% R-Sq (adj) = 92.1% and F=34.107, while the best model by (SW) was the eq. 2 with excellent statistical fit as SE= 8.89630  R-sq= 94.64% R-sq (adj)= 92.40% F=42.354. All the parameters showed insignificant role in the antitubercular activity. The molecular docking of ligands 3a-j with the cytochrome P450 14alpha-sterol demethylases (CYP51) of M. tuberculosis H37Rv was examined and the best docked pose was shown to have one hydrogen bond with PRO386. While the compound 4-Phenyl-1h-Imidazolshowed lower scores of docker energy.

Conclusion: Quantum chemical calculated parameters can be successfully used in the derived a designer QSAR. And the study indicated that predicted antitubercular activity values for pyrimidine derivative compounds can be modeled by two methods; stepwise (SW) and multiple linear regression (MLR), as well as the docking analysis showed that all compounds exhibited quite similar binding energy and compound 4 as best ligand which showed the highest binding energy and this agreement with experimental data. The most compounds understudy exhibit the best results comparison with the ligand 4-Phenyl-1h-Imidazol.All the rustles  could potentially offer a new opportunity in the design of novel properties or extended to other compounds.

Open Access Review Article

A Review on Huntington’s Disease

Avnesh Kumar, Vipin Kumar Garg

Journal of Pharmaceutical Research International, Page 1-15
DOI: 10.9734/BJPR/2016/28054

Huntington’s Disease (HD) is a progressive neurodegenerative disorder that gradually declines cognitive skills, impair memory and normal movements of affected individuals. This disease affects cerebral cortex and basal ganglia of the brain and those parts of the brain which are associated with the memory retention and motor movement. HD is an autosomal dominant inherited disease caused by the elongation of CAG repeats on the short arm of chromosome 4 at 4p16.3 in huntingtin gene (Htt gene). The mechanisms by which mutant Htt (mHtt) gene causes HD have not been known yet, however mHtt gene can impair mitochondrial function by deregulation of transcriptional processes, calcium imbalance and defective mitochondrial bioenergetics. mHtt gene of neurons affected by HD induces intracellular Ca2+ which enters in the mitochondria and opens the mitochondrial permeability transition pores (mPTP), leading to decrease in mitochondrial ATP, and neuronal cell death. The mean age of onset of this disease is 40 years but the earlier onset of the disease in childhood is known as Juvenile onset HD. HD is characterized by the motor symptoms, cognitive symptoms and psychiatric symptoms. This disease is diagnosed on the basis of symptoms found in the affected individuals and confirmation is done by the genetic testing in which CAG repeats are counted. When the CAG repeat is 40 and above, then the individual is said to be suffering from this disease.