Advancing pharmaceuticals and patient safety in Saudi Arabia: A 2030 vision initiative

Low-quality medicines deliver sub-optimal clinical outcomes and waste precious health resources. It is important to ensure that public funds are spent on healthcare technologies that meet national regulatory bodies such as the Saudi Food and Drug Authority (SFDA), quality standards for safety, efficacy, and quality. Medicines quality is a complicated combination of pre-market regulatory specifications, appropriate sourcing of ingredients (active pharmaceutical ingredient (API), excipients, etc.), manufacturing processes, healthcare ecosystem communications, and regular and robust pharmacovigilance practices. A recent conference in Riyadh, sponsored by King Saud University, sought to discuss these issues and develop specific policy recommendations for the Saudi 2030 Vision plan. This and other efforts will require more and more creative educational programs for physicians, pharmacists, hospitals, and patients, and, most importantly evolving regulations on quality standards and oversight by Saudi health authorities.     

The use of chitosan-coated flexible liposomes as a remarkable carrier to enhance the antitumor efficacy of 5-fluorouracil against colorectal cancer

Surface-coated nanocarriers have been extensively used to enhance the delivery of anticancer drugs and improve their therapeutic index. In this study, chitosan (CS)-coated flexible liposomes (chitosomes) containing 5-fluorouracil (5-FU) were designed and characterized for use as a novel approach to target colon cancer cells. 5-FU-loaded flexible liposomes (F1, F2, and F3) and 5-FU-loaded chitosomes (F4, F5, and F6) were prepared using film hydration and electrostatic deposition techniques, respectively. The particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), morphology, and in vitro drug release ability, and cytotoxicity of the formulations were determined. The results revealed that the size of chitosomes ranged from 212 to 271 nm with a positive surface charge of 6.1 to 14.7 mV, whereas the particle size of liposomes ranged from 108 to 234 nm with negative surface charges of ?2.3 to ?16.3. F3 and F6 had a spherical shape with a rough surface structure. The in vitro drug release study revealed that chitosomes retard 5-FU release as opposed to the 5-FU solution and liposomes. The cytotoxicity study using a colon cancer cell line (HT-29) showed that 5-FU-loaded chitosomes were more effective in killing cancer cells in a sustained manner than liposomes and the 5-FU solution. Chitosomes were therefore successfully developed as nanocarriers of 5-FU, with potential cytotoxicity for colorectal cancer cells.     

Novel oral dosage regimen based on self-nanoemulsifying drug delivery systems for codelivery of phytochemicals – Curcumin and thymoquinone

BackgroundCurcumin and Thymoquinone are very well-known phytochemicals for their potent anti-inflammatory and anticancer properties. The major challenges for curcumin is its poor aqueous solubility and erratic oral bioavailability.ObjectiveTo develop a novel liquid self-nanoemulsifying drug delivery system (SNEDDS) containing curcumin and thymoquinone and further converted into a solid dosage form using adsorbents Syloid® and Neusilin® as the solid carrier.MethodsThe characterization of the liquid and solid SNEDDS was performed by particle size & zeta potential analysis, scanning electron microscopy, differential scanning calorimetry, fourier transform infrared spectroscopy and X-ray powder diffraction. The drug loading, and in vitro release studies were carried out to investigate the efficiency of curcumin release from SNEDDS.ResultsThe liquid SNEDDS containing black seed oil showed excellent self-emulsification performance with transparent appearance. The results of characterization studies showed that solidification using 50% (w/w) Syloid® and Neusilin® in the liquid formulation yield free flowing powder with no agglomeration but Neusilin® produced smooth granules than Syloid® and kept the drugs stable in amorphous state. In vitro dissolution studies indicated that liquid SNEDDS formulations of F4 and its solid SNEDDS using Neusilin® provided high dissolution efficiency and reproducibility for curcumin and thymoquinone. However, Neusilin® showed higher rate of dissolution (more than 65%, p < 0.05) compared to Syloid® for curcumin.ConclusionsCurcumin loaded-SNEDDS formulation containing thymoquinone in liquid & solid dosage forms were successfully developed with an increased drug loading and dissolution rate, which could be the potential combined delivery system for various anti-inflammatory and anti-cancer treatments.     

Health literacy among patients with poor understanding of prescription drug label instructions in Saudi Arabia

IntroductionThis study conducted to assess the health literacy level among patients who have poor understanding of the medications’ labels in Saudi Arabia.MethodsThis multi-center cross-sectional study was conducted on two phases. In the 1st phase, 511 patients waiting for their medications in the outpatient pharmacies of four major hospitals in Saudi Arabia were interviewed to assess their understanding ability of the labels of five of the commonly prescribed medications. Those participants who misunderstood the medications’ labels were enrolled in the 2nd phase of the study to assess their health literacy level. The validate Arabic Single Item Literacy Screener (SILS) was used to assess the health literacy level.AnalysisThe sample characteristics were described by mean and percentage. Both Chi-square test and logistic regression model were used to figure out the association between health literacy with the main affecting factors.ResultsAlmost 38.6% (n = 197) of the participants in phase-1 misunderstood the medications’ labels. Nearly, 11.2% (n = 22) of them had low health literacy level. Participants who had low education level and low socioeconomic status were more likely to have low health literacy [adjusted odds ratio (AOR) = 2.94; 95% confidence interval (95%CI) (1.03–8.404); P-value = 0.044], [AOR = 5.28; 95%CI (1.118–24.943); P-value = 0.036], respectively.ConclusionLow health literacy was associated with low education level and low socioeconomic status of the patients.     

In vitro dissolution and bioavailability study of furosemide nanosuspension prepared using design of experiment (DoE)

Background

Nanotechnology can offer the advantages of increasing solubility and bioavailability of delivering drugs like Furosemide. The aim of the current study is to investigate the in vitro and in vivo performance of furosemide nanosuspensions.

Measuring the quality and completeness of medication-related information derived from hospital electronic health records database

ObjectiveElectronic Health Records (EHRs) database is a great source for pharmacoepidemiological research as thousands of patients’ clinical and medication information is stored in the database. However, the use of EHRs database for research purposes depends greatly on the accuracy and completeness of the data being used. This study mainly aimed to assess the completeness of EHRs patients’ medication-related information.DesignA retrospective cross-sectional study using data extracted from the EHRs database was conducted.SettingThe EHRs data was obtained from a single tertiary hospital in Saudi Arabia.Main outcome measure(s)The completeness of data was measured considering if a patients’ record contains all desired types of data (i.e., patients’ demographics, clinical diagnosis, and medication-related information).ResultsA total of 23,411 unique individuals were identified after extracting the data from the EHRs. The study found that 89.9% of the patients had a complete data (i.e., age, gender, marital status, nationality, encounter type, and clinical diagnosis). Further, 83.1% of the patients had complete medication-related information. Subgroup analysis by the encounter type indicated that the data was 91.0% complete for outpatient encounter and 93.2% complete for inpatient encounter.ConclusionThe study findings indicate that the completeness of the data varies by the desired types of data. EHRs can be a potentially great resource to conduct research to assess medication use. Further studies focusing on the content and completeness of EHRs for a specific patient population and evaluate other dimensions of EHRs data quality are needed.     

Efficacy of acetaminophen versus ibuprofen for the management of rotator cuff-related shoulder pain: Randomized open-label study

BackgroundShoulder pain related to the rotator cuff (RC) is one of the most common and bothersome musculoskeletal complaints. Pharmacologic treatment most often includes acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. However, data allowing comparison of the efficacy of these two drugs are very limited. We compared the therapeutic outcomes of acetaminophen and ibuprofen in the management of RC-related pain.MethodsThis was an open-label, two-center, active-control, prospective randomized clinical trial. Participants were assigned randomly to acetaminophen or ibuprofen treatment groups. The acetaminophen dose was 500 mg every 6–8 h, and it was 400–800 mg every 6–8 h for ibuprofen. The impact of the treatment was measured by Shoulder Pain and Disability Index (SPADI), Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) and World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaires at baseline and after 6 weeks of therapy.ResultsThirty-three patients completed the study; 20 treated with ibuprofen and 13 with acetaminophen. Patients in both groups were comparable at baseline with regard to SPADI, Quick-DASH, and WHOQOL-BREF scores. After 6 weeks of treatment, patients receiving ibuprofen, but not acetaminophen, reported an improvement in pain severity and functional activity (as measured by SPADI and Quick-DASH). Patients taking acetaminophen, but not ibuprofen, reported improvement in the physical and environmental domains of WHOQOL-BREF scores.ConclusionsIbuprofen and acetaminophen provide benefits to patients suffering from RC-related pain. However, the type of improvement perceived by patients differed between these two medications.     

Emerging frontiers of pharmacy education in Saudi Arabia: The metamorphosis in the last fifty years

The trends in the quality of biomedical education in pharmacy schools have witnessed significant changes in the 21st century. With the advent of continuous revision and standardization processes of medical curricula throughout the world, the focus has been on imparting quality education. This pedagogic paradigm has shifted to pharmacy schools. In Saudi Arabia, the concept of “medical and pharmacy education” is relatively new as mainstream pharmacy curriculum and universities were established only half a century ago. This period has seen major changes in the dimension of “pharmacy education” to keep pace with the education systems in the United States and Europe. As our knowledge and perceptions about pharmaceuticals change with time, this motivates educators to search for better teaching alternatives to the ever increasing number of enthusiastic and budding pharmacists. Recently, the academic system in Saudi Arabian Pharmacy has adopted a more clinically-oriented Pharm. D. curriculum. This paper deals with the major changes from the inception of a small pharmacy faculty in 1959, the College of Pharmacy at the King Saud University, Riyadh, to the model of progress and a prototype of pharmacy colleges in Saudi Arabia. The fifty year chronological array can be regarded as an epitome of progress in pharmacy education in Saudi Arabia from its traditional curriculum to the modern day Pharm. D. curriculum with a high population growth and expanding health care sector, the demand for qualified pharmacists is growing and is projected to grow considerably in the future. The number of pharmacy graduates is increasing each year by many folds and to meet the needs the system lays stress upon a constant revising and updating of the current curriculum from a global perspective.     

Chemical composition and protective effect of Juniperus sabina L. essential oil against CCl4 induced hepatotoxicity

The hepatoprotective activity of the total extract of Juniperus sabina L. against CCl₄ induced toxicity in experimental animals was previously reported and indicated promising results. Essential oil of J. Sabina was prepared by hydrodistillation method. Components of the oil were identified by comparison of GC-MS and retention indexes with reported data. The hepatoprotective effect of the essential oil against CCl₄ induced toxicity was studied using male Wistar rats and silymarin at 10 mg/kg p.o as standard drug. The protective effect was evaluated via serum biochemical parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyltranspeptidase (GGT), and total bilirubin as well as tissue parameters including non-protein sulfhydryl groups (NP-SH), malonaldehyde (MDA) and total protein (TP). Histopathological study was applied on the liver tissues using Mayer’s hematoxylin stain, Periodic Acid Schiff – Hematoxylin (PAS-H) and Masson trichrome technique on light microscope. Electron microscope images were also obtained for more detailed study.     

Understanding the causes of prescribing errors from a behavioural perspective

IntroductionWhile many attempts have been made to reduce prescribing errors (PEs), they persist. PE is not in itself a behaviour, but a consequence of a prescribing behaviour. Interventions aimed at prescribers should focus on understanding prescribers' behaviours.ObjectivesThe aim of this study was to use the capability, opportunity, motivation - behaviour (COM-B) model to explore the behaviours that could have caused PEs made by senior doctors in a speciality paediatric inpatient ward.MethodsA qualitative approach was used to investigate prescribers' behaviours in a 26-bed paediatric oncology ward. Error data were collected over a two-month period and were presented during focus groups with prescribers, which were audio-recorded and transcribed verbatim. Thematic analysis was used to identify contributory factors to errors, which was used to identify sources of behaviours using the COM-B model.ResultsBehaviours related to prescribers' capabilities were: prescribers' improper use of the software because of insufficient skills, and prescribers' inability to prescribe correctly because of lack of knowledge. Behaviours related to opportunities in the environment were: prescribers' inability to make an informed decision because of poor access to patient information, inability to properly complete a task because of heavy workload and interruption, and having to re-check doses frequently because of frequent change in patients' weight and surface area. Those related to motivation were: prescribers unquestioningly following recommendations and not communicating with other specialists because they over-trusted them or feared a negative reaction, and prescribers inability to complete a task because of other competing and preferable tasks at the same time.ConclusionEmploying COM-B helped in identifying causes of PEs from a new perspective. Future work could focus on mapping identified sources of behaviour and errors against appropriate intervention functions and policies in order to design more successful interventions.     

A novel Nanoformulation Development of Eugenol and their treatment in inflammation and periodontitis

ObjectiveTo prepare a novel nanoemulsion- Carbopol® 934 gel for Eugenol, in order to prevent the periodontitis.Material and methodsSpontaneous emulsification method was used for the preparation of nanoemulsion in which it contain Eugenol (oil phase), Tween-80 (surfactant), and PEG (co-surfactant). To the development of best nanoemulsion, three-factor three-level central composite design was used in which %oil; %S_mix and % water were optimized as independent variables. An optimized–nanoemulsion were converted to nanoemulsion–Carbopol® 934 gel.Results5.5% oil, 35.5% S_mix and 59.0% water were optimized as independent and dependent variables. Finally dependent variables optimized as a particle size (nm), PDI and %transmittance were observed 79.92 ± 6.33 nm, 0.229 ± 0.019, and 98.88 ± 1.31% respectively. The values of final results for dependent variables like particle size (nm), PDI and % transmittance were evaluated as 79.92 ± 6.33 nm, 0.229 ± 0.019, and 98.88 ± 1.31%, respectively. TEM and SEM showed a spherical shape of developed nanoemulsion with refractive index (1.63 ± 0.038), zeta potential (?19.16 ± 0.11), pH (7.4 ± 0.06), viscosity (34.28 ± 6 cp), and drug content of 98.8 ± 0.09%. After that a final optimized EUG–NE–Gel was assessed on the basis of their pH measurement, drug content, syringeability, and mucoadhesion on the goat buccal mucosa. Optimized EUG-NE-Gel (Tween-80 and Carbopol® 934 used) showed the results, to improve the periodontal drug delivery of EUG in future.ConclusionEUG-NE-Gel showed a significant role in anti-inflammatory activity, analgesic, and anesthetic, antibacterial, and treatment of periodontal disease.     

Molecular and biochemical monitoring of the possible herb-drug interaction between Momordica charantia extract and glibenclamide in diabetic rats

Momordica charantia is used in folk medicine to manage diabetes mellitus. In this study, we investigated the possible herb-drug interaction between M. charantia fruit extract (MCFE) and glibenclamide (GLB) in streptozotocin-diabetic rats. Rats were divided into 7 groups. The 1st group received 3% Tween 80. The 2nd–5th groups were diabetic rats received vehicle, GLB (5 mg/kg), MCFE (250 and 500 mg/kg), respectively. The 6th–7th groups administered GLB plus MCFE (250 and 500 mg/kg), respectively. After 8 weeks, fasting blood glucose (FBG), insulin and glycosylated hemoglobin (HbA1c) levels were assessed. Histopathological and immunohistochemical examinations of the pancreases were done. Quantitative RT-PCR was used to analyze hepatic mRNA expression of insulin receptor (INR), glucose transporter 2 (Slc2a2) and peroxisome proliferator-activated receptor α (PPAR-α) genes. All medicaments greatly reduced FBG in diabetic rats when compared with diabetic control group. GLB plus MCFE combination was better than GLB alone in improving levels of insulin and HbA1c. All medicaments restored insulin content of pancreatic β-cells and reduced glucagon and somatostatin of alpha and delta endocrine cells. Moreover, GLB plus MCFE-500 was the most efficient in restoring INR, Slc2a2 and PPAR-α mRNA expression to their normal levels. In conclusion, MCFE in combination with GLB gives greater glycemic improvement than GLB monotherapy.     

Effect of olive leaves extract on the antidiabetic effect of glyburide for possible herb-drug interaction

The concomitant use of olive leaves (OL) and glyburide (GLB) is a possible therapy for diabetic patients. However, there is no report about the effect of OL on the antidiabetic effect of GLB till now. In the current study, the possible interaction of olive leaves extract (OLE) with GLB was assessed to determine if there was any pharmacological benefit over GLB alone. Seven groups of male Sprague Dawley rats were used. Normal rats of the 1st group treated with 2 mL/kg of 3% Tween 80 (vehicle). The 2nd–5th groups were diabetic rats received vehicle, GLB (5 mg/kg), OLE low dose and OLE high dose respectively, while the 6th–7th groups administered combinations of GLB plus OLE low dose and GLB plus OLE high dose, respectively. All treatments were administered orally once daily for 8 weeks.The use of GLB+OLE-500 obviously improved fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c) in diabetic rats (95.5 ± 5.55 mg/dL, 6.8 ± 0.16 mg/dL and 6.1 ± 0.29%, respectively) compared to those treated with GLB monotherapy (140.0 ± 6.36 mg/dL, 5.4 ± 0.19 mg/dL and 7.0 ± 0.20%, respectively). The lipid profile [triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)] was significantly improved in diabetic rats exposed to GLB+OLE-500 (35.6 ± 1.51 mg/dL, 48.5 ± 2.74 mg/dL, 25.1 ± 1.21 mg/dL and 17.0 ± 0.82 mg/dL, respectively) in comparison with diabetic group exposed to GLB alone (43.2 ± 2.15 mg/dL, 56.8 ± 2.14 mg/dL, 18.6 ± 0.96 mg/dL, 23.0 ± 1.26 mg/dL, respectively). Additionally, the benefit impacts of GLB+OLE-500GLB+OLE-500 therapy on the antioxidant and lipid peroxidation parameters in the pancreatic tissues of diabetic rats were higher than those of GLB monotherapy. Moreover, GLB plus OLE-500 combination had the greatest effect on restoration of the insulin content of Beta (β) cells and reduction of the glucagon and somatostatin of Alpha (α) and Delta (δ) endocrine cells in the pancreatic islets among the different treatment. The current study suggests that OL and GLB combination could cause herb-drug interactions through modulation of insulin receptor (INR), glucose transporter 2 (Slc2a2) and peroxisome proliferator-activated receptor α (PPAR-α) genes expression in the liver of diabetic rats.     

Olive leaves extract attenuates type II diabetes mellitus-induced testicular damage in rats: Molecular and biochemical study

Diabetes mellitus (DM) has emerged as a public healthcare problem. Sustained hyperglycemia has been linked with many complications including impaired male fertility Olive tree (Olea europaea L.) leaves have been extensively used in traditional remedies worldwide to control blood glucose level in DM. In this study, the beneficial role of olive leaves extract (OLE) was investigated to combat diabetes-induced adverse effect on testicular tissues. Thirty male Wistar rats were divided into 5 equal groups: normal control group, streptozotocin (STZ)-diabetic group and diabetic groups which were given glibenclamide (GLB) or OLE at 250 and 500?mg/kg for 9?weeks to investigate the efficiency of olive leaves extract (OLE) in reducing the deleterious effect of diabetes on the reproductive system of male rats. Rats were checked for serum glucose, insulin, testosterone and gonadotropins. Also, testicular antioxidants, epididymal sperm characteristics and testicular histopathology were assessed. Expression of the testicular steroidogenic enzymes, cholesterol side-chain cleavage enzyme (P450 scc) and 17β-hydroxysteroid dehydrogenase (17β-HSD) was examined. Moreover, androgen receptor and proliferating cell nuclear antigen (PCNA) protein immunohistochemistry were assessed in testes. STZ-induced diabetes significantly increased serum glucose. However, STZ significantly decreased serum levels of insulin, testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Marked reductions in testicular antioxidants with elevated malondialdehyde (MDA) parallel with deterioration of the testicular histoarchitecture and epididymal sperm characteristics were recorded. Administration of GLB or OLE (250 and 500?mg/kg) resulted in a significant recovery of the above mentioned parameters in STZ-diabetic rats. Interestingly, OLE shows greater glycemic improvement and testicular protection than GLB with the highest percentage protection exhibited by the OLE high dose. Furthermore, OLE significantly induced testicular steroidogenesis in diabetic rat as evidenced by elevated P450 scc and 17β-HSD mRNA expression. The study proves that OLE possesses a potential protective role against diabetes-induced reproductive disorders, which may be due to its antioxidant activity and its ability to normalize testicular steroidogenesis.     

Improving medication information transfer between hospitals,skilled-nursing facilities,and long-term-care pharmacies for hospital discharge transitions of care: A targeted needs assessment using the Intervention Mapping framework

Introduction

Patients transitioning from the hospital to a skilled nursing home (SNF) are susceptible to medication-related errors resulting from fragmented communication between facilities. Through continuous process improvement efforts at the hospital, a targeted needs assessment was performed to understand the extent of medication-related issues when patients transition from the hospital into a SNF, and the gaps between the hospital's discharge process, and the needs of the SNF and long-term care (LTC) pharmacy. We report on the development of a logic model that will be used to explore methods for minimizing patient care medication delays and errors while further improving handoff communication to SNF and LTC pharmacy staff.