Development of the Emirates Multi-Criteria Decision Analysis Tool for Orphan Drugs.

Background The number of orphan drug approvals is currently increasing globally. This creates a significant burden on payers and healthcare systems. This study aimed to create a multi-criteria decision analysis (MCDA) tool for evaluating orphan drugs within the United Arab Emirates (UAE). The intended result of the tool is to provide evidence-based guidance to decision-makers in reimbursement and procurement decisions. Methods We conducted a literature search and local expert interviews to identify relevant preliminary criteria for the MCDA tool. Then we conducted a structured consensus-building session for healthcare experts and decision-makers in the UAE to develop the Emirati MCDA tool for orphan drugs. The experts voted for the criteria to be included in the tool and their ranking according to importance, as well as the weight of each criterion and its scoring function. To improve understanding and facilitate the voting process, experts were provided with a brief illustration of similar tools conducted in other countries before the voting sessions. Finally, the tool was developed in a Microsoft Excel sheet (Microsoft Corporation, Redmond, Washington, United States), and it was validated and tested based on real case studies, then it was fine-tuned accordingly based on the experts' discussions. The final tool was provided to the attendees to guide their decisions in the reimbursement and procurement of orphan drugs. Results The created tool provides a score for each analyzed orphan drug based on its value. Ten criteria were included in the final MCDA tool. These were cost-effectiveness (25.1% of the weight), magnitude of health gain (20.1%), availability of therapeutic alternative (14.3%), disease severity (11%), budget impact (7.9%), disease rarity (5.6%), strength of clinical evidence (5.6%), burden on households (4.5%), indication uniqueness (3.2%), and patients' age (2.6%). Conclusions Implementation of evidence-based healthcare necessitates assessing the fair value of each health technology. Addressing the high unmet medical needs and improving healthcare for patients with rare diseases are priorities within the UAE. The created Emirates MCDA tool for orphan drugs has the potential to help decision-makers implement value-based and evidence-based reimbursement decisions for orphan drugs.

Environmental estrogen exposures alter molecular signaling in immune cells that promote the development of childhood asthma.

Environmental estrogens (EEs) are associated with an increased prevalence of asthma. These epigenetic alterations of the immune cells may explain the multigenerational effects on asthma development. We hypothesized that exposure to immune cells enhances allergic sensitization by initiating signaling in these cells. Human T cell lines (TIB-152, CCL-119) were exposed to varying concentrations of estradiol, bisphenol A, bisphenol S, or bisphenol A + estradiol. H3K27me3, phosphorylations of EZH2 (pEZH2), AKT (pAKT), and phosphatidylinositide 3-kinase (pPI3K) were assessed. pAKT and pPI3K were decreased in response to some of the concentrations of these exposures in both cell lines. It is likely that EEs exposure to immune cells is one of the factors in the increase in the prevalence of asthma.

In vitro dissolution and in vivo bioavailability of six brands of ciprofloxacin tablets administered in rabbits and their pharmacokinetic modeling.

This study was undertaken to assess the in vitro dissolution and in vivo bioavailability of six brands of ciprofloxacin oral tablets available in the UAE market using rabbits. The in vitro dissolution profiles of the six ciprofloxacin products were determined using the USP dissolution paddle method. Pharmacokinetic modeling using compartmental and noncompartmental analysis was done to determine the pharmacokinetic parameters of ciprofloxacin after single-dose oral administration. In vitro release study revealed that the amount of ciprofloxacin released in 20 minutes was not less than 80% of the labeled amount which is in accordance with the pharmacopoeial requirements. All tested products are considered to be very rapid dissolving except for formulae A and D. Ciprofloxacin plasma concentration in rabbits was best fitted to a two-compartment open model. The lowest bioavailability was determined to be for product A (93.24%) while the highest bioavailability was determined to be for product E (108.01%). Postmarketing surveillance is very crucial to ensure product quality and eliminating substandard products to be distributed and, consequently, ensure better patient clinical outcome. The tested ciprofloxacin generic products distributed in the UAE market were proven to be of good quality and could be used interchangeably with the branded ciprofloxacin product.

Development of coated beads for oral controlled delivery of cefaclor: In vitro evaluation.

The aim of the present study was to develop and characterize coated chitosan-alginate beads containing cefaclor as a controlled release delivery system. Coated cefaclor beads were prepared by solvent evaporation techniques. Beads were found to be intact and spherical in shape. Their size range was 1.05 to 2.06. The loading efficiency showed maximum value when the concentration of cefaclor, chitosan and PEG 400 was 10 % (m/V), 0.5 % (m/V) and 2 % (V/V), respectively. Best retardation of cefaclor release from chitosan-alginate beads was achieved by coating with 15 % of shellac in formula F19. A significant antimicrobial activity (p < 0.05) against Staphylococcus aureus and Klebsiella pneumoniae was observed for formula F19 compared to the standard antibiotic disc. Furthermore, the simulated plasma profile showed the superiority of F19 in sustaining drug release for more than 12 h. Therefore, shellac coated chitosan-alginate beads could be considered a successful controlled release oral cefaclor dosage form.

Development and evaluation of chitosan microspheres for tetanus, diphtheria and divalent vaccines: a comparative study of subcutaneous and intranasal administration in mice.

CONTEXT: There is a need to use the new technologies to induce immunity with minimum number of vaccination sessions to ensure compliance with reducing cost. OBJECTIVES: To develop single shot vaccines of tetanus, diphtheria and divalent toxoids microsphere's formulations and to induce their immune response after intranasal and subcutaneous administration in mice. MATERIALS AND METHODS: The microspheres were prepared using different concentrations of chitosan. Microsphere's morphology, particle size analysis, encapsulation efficiency and antigen integrity were performed and the best formulations were selected for in vitro and in vivo testing in mice. RESULTS: The developed microspheres have a yield percent of 70.3-91.5%. In vitro release of antigens indicated that tetanus release was increased up to 75 and 81% post T5 and TD5 formulations respectively, whereas diphtheria cumulative release increased up to 74 and 69% post D3 and TD5, respectively. DISCUSSION: Antibody levels produced were lower than that obtained from alum adsorbed vaccine but higher than the minimum level required to induce immunogenicity (>0.01 IU/mL). The subcutaneous route of administration was superior over the intranasal route in producing higher antibody levels. CONCLUSION: Chitosan microspheres were developed successfully and prove that chitosan represents a good candidate for vaccines delivery.

Impact of chitosan as a disintegrant on the bioavailability of furosemide tablets: in vitro evaluation and in vivo simulation of novel formulations.

To determine the effect of chitosan, starch powder, polyvinylpyrrolidone (PVP), Avicel PH 101 powder, Avicel PH 102 granules as a function of different concentrations on the solubility, disintegration and hence dissolution of furosemide from immediate release tablet dosage forms. The tablets were prepared by the wet granulation method and evaluated for hardness, friability, disintegration and in vitro dissolution. Chitosan 7% w/w showed the fastest disintegration of furosemide tablets among the other disintegrants studied. This was attributed to its highest swelling properties and velocity constant of water uptake. The step of adding chitosan during tablet preparation had a great effect on the physical properties and dissolution profiles of the prepared tablets with external addition of chitosan showed best results compared to best results comparing to internal-external or internal addition. The most appropriate force of compression was 4ton/cm(2). The selected formula F15 containing 7% w/w chitosan was successful and showed a high significant (p<0.001) enhancement in disintegration and dissolution behaviors of furosemide tablets in comparison with the commercially available Furosemide ® tablets. These results were supported by the simulated data where F15 formula showed the highest plasma concentration C-max 1.89mcg/mL after 0.5 hr compared to C-max 1.05mcg/mL after 1hr for the reference. The present study demonstrated that chitosan is a very good candidate to be used as a tablet disintegrant and was able to enhance the dissolution of poorly absorbable drugs.

Imperative to consider multiple initiatives to maximize prescribing efficiency from generic availability: case history from Abu Dhabi.

INTRODUCTION: Pharmaceutical expenditure has risen rapidly in Abu Dhabi, resulting in policies surrounding generics. However, various circumstances will reduce potential savings, including pharmacists still being free to dispense either originator or branded generics and be fully reimbursed. OBJECTIVES: To research the changes in utilization patterns of proton pump inhibitors (PPIs) and lipid-lowering drugs before and after combined reforms on generics; and subsequently, calculate potential savings based on 'best practices' among Western European countries. METHODS: An uncontrolled before-and-after observational study of utilization and expenditure of PPIs, statins and ezetimibe between 2004 and 2010, as well as up to 12 months before the first generic policy, to 1 year after the second generic policy, was carried out. Utilization was converted to defined daily doses (DDDs; 2011 DDDs) and DDDs/1000 inhabitants per day. Expenditure/DDD was calculated for omeprazole and simvastatin. RESULTS: PPI utilization rose by 6.5-fold from 2004 to 2010, principally driven by increased utilization of patent-protected PPIs, although more recently stabilization in esomperazole utilization has occurred. Similar changes were seen for statins. Introduction of best practices would reduce PPI expenditure in 2010 by 32.8 million United Arab Emirates dirham (AED; €6.26 million) and statins by over 27 million AED (€5.15 million). CONCLUSION: Limited demand-side measures led to increased utilization of patent-protected products in Abu Dhabi following the generic reforms. Successful measures will release considerable resources.

Meloxicam ß-cyclodextrin transdermal gel: physicochemical characterization and in vitro dissolution and diffusion studies.

The aim of the study was to develop a Meloxicam (ME) transdermal gel formulations based on complexation with ß-cyclodextrin. ME ß-Cyclodextrin gel formulations were prepared using four different gel bases with different concentrations and different permeation enhancers. The developed formulations were examined for their in vitro characteristics and their diffusion through a mouse skin. The gel formulations were prepared successfully. Physicochemical characterization of ME ß-CD complex in solution state by phase solubility revealed 1:1 M complexation of ME with ß-Cyclodextrin. ME release profiles from the inclusion complex were superior over ME alone. Hydroxypropyl methyl cellulose 15% w/w gel base was proven to be a suitable base for ME inclusion complex formulation as it provides a high drug release than other studied bases. ME ß-CD complex gel formulations containing oleic acid (1% w/w) or (5% w/w) cineol used as permeation enhancers in (15% w/w) HPMC gel base were proven to provide a higher diffusion rate of the drug through the mouse skin. This is very promising in providing analgesic activity of meloxicam via topical route of administration.

Influenza vaccination: healthcare workers attitude in three Middle East countries.

BACKGROUND: Healthcare workers (HCWs) pose a potential risk of transmitting communicable diseases in the hospital settings where they usually work. This study aims to determine the current influenza vaccination rates among HCWs in three Middle East countries namely United Arab Emirates (UAE), Kuwait and Oman, and also to identify the different variables associated with the noncompliance of HCWs to the recommendations of the Advisory Committee on Immunization Practices (ACIP) set in those countries. METHODS: 1500 questionnaires were distributed to health care workers in the three countries during the period of July-October 2009. RESULTS: Among 993 respondents, the vaccination rate was 24.7%, 67.2% and 46.4% in UAE, Kuwait and Oman, respectively. The different motivating factors that influenced the health care workers to take the vaccine was assessed and found that the most common factor that influenced their decision to take the vaccine was for their self protection (59%). On the other hand, the most common reason that discouraged HCWs to take the vaccine was "lack of time" as reported by 31.8% of the respondents. Other reasons for not taking the vaccine were unawareness of vaccine availability (29.4%), unavailability of vaccine (25.4%), doubts about vaccine efficacy (24.9%), lack of information about importance (20.1%) and concerns about its side effects (17.3%). CONCLUSIONS: influenza immunization by healthcare workers in the studied countries was suboptimal which could be improved by setting different interventions and educational programs to increase vaccination acceptance among HCWs.

Pharmacokinetics of terbinafine after single oral dose administration in red-tailed hawks (Buteo jamaicensis).

To determine pharmacokinetic parameters of orally administered terbinafine hydrochloride for potential treatment of aspergillosis in raptors, 10 adult red-tailed hawks (Buteo jamaicensis) were used in single dose trials by using 15, 30, and 60 mg/kg doses with a 2-week washout period between trials. After administration of 15 mg/kg terbinafine, mean (+/- SD) plasma concentration peaked in approximately 5 hours at 0.3 +/- 0.24 microg/mL, whereas a 30 mg/kg dose resulted in peak mean (+/- SD) plasma concentration of 1.2 +/- 0.40 microg/mL in 3 hours and a 60 mg/kg dose resulted in mean (+/- SD) concentration of 2.0 +/- 0.75 microg/mL in 5 hours. The volume of distribution decreased with increasing doses, averaging 76.8 +/- 38.06 mL/kg for the 15 mg/kg dose and falling to 55.2 +/- 17.4 mL/kg for the 30 mg/kg dose. This suggests that terbinafine accumulated in deep tissues, limiting further distribution at higher doses. The harmonic mean (+/- SD) half-life was biphasic, with initial values of 14.7 +/- 6.67 hours, 17.5 +/- 8.7 hours, and 13.3 +/- 5.03 hours for 15, 30, and 60 mg/kg doses, respectively. A rapid first-elimination phase was followed by a slower second phase, and final elimination was estimated to be 161 +/- 78.2 and 147 +/- 65.6 hours for 15 and 30 mg/kg doses, respectively. Linearity was demonstrated for the area under the curve but not for peak plasma concentrations for the 3 doses used. Calculations based on pharmacokinetic parameter values indicated that a dosage of 22 mg/kg terbinafine q24h would result in steady-state trough plasma concentrations above the minimum inhibitory concentration of terbinafine (0.8-1.6 microg/mL). This dosage is recommended as a potential treatment option for aspergillosis in raptors. However, additional research is required to determine both treatment efficacy and safety.

Pharmacists’ attitude, perceptions and knowledge towards the use of herbal products in Abu Dhabi, United Arab Emirates / Actitud, conocimiento y percepciones de los farmacéuticos hacia el uso de plantas medicinales en Abu Dhabi, Emiratos Árabes Unidos

Objective: The purpose of the study was to assess pharmacists' current practice, perception and knowledge towards the use of herbal products in Abu Dhabi, United Arab Emirates (UAE). The study assessed the need for incorporating herbal medicine as a separate topic in under- graduate pharmacy student curricula. Methods: The study was done on 600 pharmacists employed in Abu Dhabi, who were contacted electronically, out of which 271 had completed the survey. The data was collected using a structured questionnaire. Results: Pharmacists' use of herbal products is high in the UAE, as they have a high belief on the effectiveness of herbal products, and only age was found to be the most predominant variable that was influencing pharmacists' personal use of herbal products (p-value=0.0171). Pharmacists were more knowledgeable on the uses/indications of herbal products (47%) rather than on other areas. Knowledge of the dispensing mode (prescription only or over the counter medicines) mandated by the Ministry of Health was quite good, however, it is to be noted that the source of information on the dispensing mode was provided by medical representatives (48%). Knowledge of dispensing mode of herbal products was found to be significantly influenced by the place of work with more knowledge of the dispensing mode by pharmacists working in the private sector (p-value 0.0007). The results from the study also underscores the need for including herbal medicine as a separate topic in pharmacy college curriculum and to provide for more seminars and continuing pharmacy education programs targeting pharmacists in the Emirate of Abu Dhabi. Conclusions: Pharmacists need to be informed on indications, drug interactions, adverse events and precautions of herbal products. Concerned bodies must also provide them with regular continuing education programs apart from putting their efforts to incorporate relevant topics on herbal medicine in the pharmacy students' curriculum (AU)

Objetivo: El propósito del estudio fue evaluar la práctica actual de los farmacéuticos, las percepciones y el conocimiento sobre el uso de plantas medicinales en Abu Dhabi, Emiratos Árabes Unidos (EAU). El estudio evaluó la necesidad de incorporar las plantas medicinales como materia separada en el currículo de los estudiantes de farmacia. Métodos: El estudio se realizó en 600 farmacéuticos empleados en Abu Dhabi, que fueron contactados electrónicamente, de los que 271 completaron la encuesta. Los datos se recogieron utilizando un cuestionario estructurado. Resultados: El uso de plantas medicinales es elevado en EAU, ya que existe una creencia sobre la alta efectividad de estos productos, y sólo la edad fue la variable más predominante que influenció el uso personal de plantas medicinales por los farmacéuticos (p-value=0.0171). Los farmacéuticos tenían más conocimientos de los usos/indicaciones de las plantas medicinales (47%) que de otras áreas. El conocimiento del modo de dispensación (prescripción o over-the-counter) obligado por el Ministerio de Salud era bastante bueno, sin embargo se vio que la fuente de información para la dispensación eran los representantes médicos (48%). El conocimiento del modo de dispensación pareció estar influenciado significativamente por el lugar de trabajo, con mayor conocimiento los que trabajaban en el sector privado (p-value 0.0007). Los resultados del estudio también señalan la necesidad de incluir las plantas medicinales como materia separada en el currículo de la facultad de farmacia y de proporcionar más seminarios y programas de formación continua enfocados hacia los farmacéuticos del Emirato de Abu Dhabi. Conclusiones: Los farmacéuticos necesitan estar informados de indicaciones, interacciones, efectos adversos y precauciones de las plantas medicinales. Las entidades relacionadas también deben proporcionarles programas de formación continua regulares además de incluir los aspectos relevantes de las plantas medicinales en el currículo de los estudiantes de farmacia (AU)

Professional practices and perception towards rational use of medicines according to WHO methodology in United Arab Emirates / Prácticas profesionales y percepción sobre el uso racional de medicamentos según la metodología de OMS en Emiratos Árabes Unidos

Inappropriate prescribing reduces the quality of medical care and leads to a waste of resources. No study has been reported concerning rational drug use in United Arab Emirates, UAE, recently. Objectives: 1. assessing patterns of use and defining problems regarding the rational drug use. 2. Setting baseline situational analysis study for practices in the health care system relevant to drug use. Method: A descriptive pilot study, consisting of pharmacists, physicians and patients (100 of each of category) from four private hospitals, (12) medical clinics, (80) community pharmacies in addition to 150 prescriptions. A questionnaire of three sections was designed to include WHO indicators regarding patients, facility and prescribing patterns that are relevant to rational drug use was carried out in four emirates of the UAE in the period December 2008-February 2009. Results: Consultation and dispensing times were 10 (SD=2.75) min and 68 (SD=9.7) seconds, respectively. Average no. of drugs per prescription was (2.9 + 0.97), % of prescriptions using generic name (7.35%), % of antibiotic containing prescriptions (31.1%), % of injection containing prescriptions (2.9%), adherence to Standard Treatment Protocols (46%), adherence to the essential drug list (64%), patient's knowledge of correct dosage (55%), adequately labeled drugs (45%), patient's information (65%). Conclusions: Several areas of deficiency in rational drug use had been defined in the private sector through UAE that can be remedied through adopting several strategies such as adherence to national standard treatment guidelines and essential drug list based on treatments of choice, interaction between health care system and providing drugs information to consumers (AU)

La prescripción inapropiada reduce la calidad de la atención médica y lleva a un desperdicio de recursos. No se ha escrito ningún estudio sobre el uso racional de medicamentos en los Emiratos Árabes Unidos (EAU) recientemente. Objetivos: 1, evaluar los patrones de uso y definir problemas en el uso racional de medicamentos. 2, establecer la situación de base para el estudio de prácticas en el sistema sanitario relevantes al uso de medicamentos. Métodos: Estudio piloto descriptivo, incluyendo farmacéuticos, médicos y pacientes (100 de cada categoría) de 4 hospitales privados, (12) consultas médicas, (80) farmacias comunitarias además de 150 prescriptores. Se diseñó un cuestionario de tres secciones incluyendo los indicadores de la OMS relativos a pacientes, local y patrones de prescripción relevantes al uso racional de medicamentos para los cuatro emiratos de EAU en el periodo de diciembre 2008 a febrero 2009. Resultados: los tiempos de consulta y dispensación fueron e 10 (SD=2,75) minutos y 68 (SD=9,7) segundos respectivamente. La media de medicamentos por receta fue de 2,9 (SD=0,97), el 7,35% de las recetas usaban nombres genéricos, el 31,1% contenía antibióticos, el 2,9% contenía inyectables, el 46% cumplía los protocolos estándar de tratamiento, el 64% contenía medicamentos de la lista de medicamentos esenciales, en el 55% había conocimiento de los pacientes de la dosis correcta, en el 45 hubo etiquetado adecuado de los medicamentos, y en el 65% hubo información a los pacientes. Conclusiones: Se identificaron varias deficiencias en cuento al uso racional de medicamentos en el sector privado en los EAU que pueden remediarse adoptando algunas estrategias como el cumplimiento de las guías de estándares nacionales tratamientos y la lista de medicamentos esenciales para la elección de tratamientos, la interacción entre el sistema sanitario y los proveedores de información sobre de medicamentos a los consumidores (AU)

Pharmacists' attitude, perceptions and knowledge towards the use of herbal products in Abu Dhabi, United Arab Emirates.

OBJECTIVE: The purpose of the study was to assess pharmacists' current practice, perception and knowledge towards the use of herbal products in Abu Dhabi, United Arab Emirates (UAE). The study assessed the need for incorporating herbal medicine as a separate topic in under- graduate pharmacy student curricula. METHODS: The study was done on 600 pharmacists employed in Abu Dhabi, who were contacted electronically, out of which 271 had completed the survey. The data was collected using a structured questionnaire. RESULTS: Pharmacists' use of herbal products is high in the UAE, as they have a high belief on the effectiveness of herbal products, and only age was found to be the most predominant variable that was influencing pharmacists' personal use of herbal products (p-value=0.0171). Pharmacists were more knowledgeable on the uses/indications of herbal products (47%) rather than on other areas. Knowledge of the dispensing mode (prescription only or over the counter medicines) mandated by the Ministry of Health was quite good, however, it is to be noted that the source of information on the dispensing mode was provided by medical representatives (48%). Knowledge of dispensing mode of herbal products was found to be significantly influenced by the place of work with more knowledge of the dispensing mode by pharmacists working in the private sector (p-value 0.0007). The results from the study also underscores the need for including herbal medicine as a separate topic in pharmacy college curriculum and to provide for more seminars and continuing pharmacy education programs targeting pharmacists in the Emirate of Abu Dhabi. CONCLUSIONS: Pharmacists need to be informed on indications, drug interactions, adverse events and precautions of herbal products. Concerned bodies must also provide them with regular continuing education programs apart from putting their efforts to incorporate relevant topics on herbal medicine in the pharmacy students' curriculum.

Professional practices and perception towards rational use of medicines according to WHO methodology in United Arab Emirates.

UNLABELLED: Inappropriate prescribing reduces the quality of medical care and leads to a waste of resources. No study has been reported concerning rational drug use in United Arab Emirates, UAE, recently. OBJECTIVES: assessing patterns of use and defining problems regarding the rational drug use.Setting baseline situational analysis study for practices in the health care system relevant to drug use. METHOD: A descriptive pilot study, consisting of pharmacists, physicians and patients (100 of each of category) from four private hospitals, (12) medical clinics, (80) community pharmacies in addition to 150 prescriptions. A questionnaire of three sections was designed to include WHO indicators regarding patients, facility and prescribing patterns that are relevant to rational drug use was carried out in four emirates of the UAE in the period December 2008-Febreuary 2009. RESULTS: Consultation and dispensing times were 10 (SD=2.75) min and 68 (SD=9.7) seconds, respectively. Average no. of drugs per prescription was (2.9 + 0.97), % of prescriptions using generic name (7.35%), % of antibiotic containing prescriptions (31.1%), % of injection containing prescriptions (2.9%), adherence to Standard Treatment Protocols (46%), adherence to the essential drug list (64%), patient's knowledge of correct dosage (55%), adequately labeled drugs (45%), patient's information (65%). CONCLUSIONS: Several areas of deficiency in rational drug use had been defined in the private sector through UAE that can be remedied through adopting several strategies such as adherence to national standard treatment guidelines and essential drug list based on treatments of choice, interaction between health care system and providing drugs information to consumers.

Development of novel spray coated soft elastic gelatin capsule sustained release formulations of nifedipine.

Nifedipine release from coated commercially available immediate release soft elastic gelatin capsules was investigated. Capsules were spray coated using two different polymeric combinations, ethylcellulose and hydroxypropylmethylcellulose or pectin, at different coating loads. In vitro drug release studies were conducted in three different dissolution media: with gastric pretreatment, without gastric pretreatment, and in water to investigate the pH effect on nifedipine release. Convolution of in vitro dissolution data for selected formulations and commercially available sustained release nifedipine formulations showed that the tested formulations provided release profiles of nifedipine that are very promising in terms of desirable sustained release formulations.