Pharmacoepidemiology

Background: Estimates of prevalence are known to be affected by the design of cross-sectional studies. A pan-European study provided an opportunity to compare the effect of two cross-sectional study designs on estimates of medicines use. Methods: A Service evaluation survey (SES) and a web-based point-prevalence study (PPS) were conducted as part of a European study of neonatal exposure to excipients. Neonatal units from all European Union countries plus Iceland, Norway, Switzerland and Serbia were invited to participate. All medicines prescribed to neonates were recorded during three-day and one-day study periods in the SES and PPS, respectively. In the PPS individual demographic and prescription data were also collected. To compare the probabilities that a particular medicine would be reported by each study multilevel mixed effects logistic regression models with crossed random effects were applied. The relationship between medicines exposure at the unit and individual levels in the PPS data was assessed using polynomial regression with square root transformation. Results: Of 31 invited countries 20 and 21 with 115 and 89 units joined the SES and PPS, respectively. Out of 5,572,859 live births in invited countries in 2010 a higher proportion was covered by units participating in the SES compared to the PPS (11% vs 6%, respectively; OR 1.89; 95% CI 1.87-1.89). A greater number of active pharmaceutical ingredients (API), manufacturers and trade names were registered in the SES compared to the PPS. High correlation between the two studies in frequency of use for each specified API was seen (R 2 = 0.86). The average probability of a department to use a given API was greater in the SES compared to the PPS (OR 2.36; 95% CI 2.05-2.73) with higher frequency of use and longer average duration of prescription further increasing the difference. The polynomial regression model described the correlation between APIs exposure on unit and individual level well (R 2 = 0.93). Conclusion: The simple data structure and longer study period of the SES resulted in improved recruitment and higher likelihood of capture for a given API. The frequency of use at the unit level appears a good surrogate of individual exposure rates.

The belief that one is especially sensitive to the actions and side effects of medicines can influence treatment adherence and side-effect reporting. In this study, we investigated the prevalence of perceived medication sensitivity in the general population and its relationship to symptom complaints, information seeking about medications, use of medical care and demographic factors. A nationally representative sample of 1000 New Zealand residents completed the Perceived Sensitivity to Medicines scale and symptoms experienced during the previous 7 days. Demographic data and medical visits, medication use and information seeking about medicines were also collected. Over 20% of the general population reported being very sensitive to the effects of medication (20.2%) and that small amounts of medicines can upset their body (25.3%). Participants who reported high levels of perceived sensitivity to medicines reported significantly more symptoms (M = 9.54, SE = 0.47) than people with low (...

Objectives: To compare data on statin utilisation and costs across Europe from routine administrative databases with those from a commercial source. Methods: Observational study in European Union member states and Norway. Comparison of data collected from national administrative databases used to reimburse pharmacists and data from a standard commercial source (Intercontinental Marketing Services Health): detailed data by drug for the year 2000. Results: There were differences among the data from administrative databases and those from the commercial source; these differences were of a consistent pattern in each country. In general, the commercial data recorded greater utilisation (reflecting both public and private use, range from 0 to +55%, median +15%), lower cost per defined daily doses (as commercial data sources used ex-factory price rather than expenditure to the state used in administrative databases, range from À70% to -6%, median À39%) and similar utilisation per 1000 head of population per day (range from À15 to +47%, median À1%).

Background: Polypharmacy is an important patient safety concern and has been associated with increased adverse drug reactions, hospitalization, and mortality in the elderly. However, few studies have analyzed the association between socioeconomic position (SEP) and the extent of drug use in older people.

Objectives: To determine the prevalence of inappropriate medication prescribing in Middle Eastern community-dwelling elderly persons, and to determine factors associated with inappropriate prescribing. Methods: Prescriptions from 3,000 elderly-patient visits (≥65 years) to physicians in Isfahan, Iran were collected between September and December 2002; only the first patient visit was considered in the study. Inappropriate prescriptions were defined according to Beers' explicit criteria (1997). The presence of at least one drug-drug interaction (DDI) and at least one drugclass duplication within each patient visit was also determined. Multivariate analyses were performed to determine factors associated with receiving at least one inappropriate medication. These factors included age, gender, number of prescribed medications per visit, DDIs, duplications, and physician's number of years of experience. Similar analyses were performed to determine whether these factors were associated with a composite index (defined as having at least one of the following: receiving at least one inappropriate prescription, DDI, or duplication). Results: The mean age of our cohort was 72.6 (±5.7) years, and 1,735 (57.8%) were females. A total of 829 (27.6%) patients received at least one inappropriate prescription, 285 (9.5%) had at least one DDI during the visit, and 746 (24.9%) had at least one duplication during the visit. The three most inappropriately prescribed medication classes were antihistamines (29%), non-steroidal anti-inflammatory agents (23%) and benzodiazepines (16%). In multivariate analyses, the number of prescribed medications per visit was the only factor significantly associated with receiving at least one inappropriate prescription (OR 1.24; 95%CI: 1.16-1.32); analyses using the composite index as outcome gave similar results (OR: 1.70; 95%CI: 1.60-1.80). Conclusion: Our findings indicate a high prevalence of inappropriate prescribing in elderly patients. Given the potential severity of this problem, further steps need to be implemented to prevent this occurrence.

The aim of the present study was to formulate and evaluate Metformin HCl microspheres to produce a drug delivery system with better pharmaceutical and therapeutic properties. Metformin HCl microspheres were prepared by using ethyl cellulose as a release retardant polymer by solvent evaporation method .Formulations F1, F2 and F3 were prepared using ethyl cellulose in the drug polymer ratio of 1:1, 1:2 and 1:3. A plasticizer (N-dibutyl phthalate) was added in formulations F4,F5 and F6 .The prepared microspheres were evaluated for the parameters like Percentage yield, Particle size analysis, Micromeritic properties like angle of repose, bulk density, tapped density, compressibility index, Hausner’s ratio, melting point determination, drug content estimation, microencapsulation efficiency and in vitro drug release studies. The in vitro release of Metformin HCl was slow and extended over longer period of time. As the concentration of polymer was increased, the drug release was decreased. The drug release was found to be slow in formulations F4, F5 and F6 when compared to F1, F2 and F3. Thus the study clearly indicated a promising potential of sustained release Metformin HCl microspheres containing ethyl cellulose as rate controlling polymer for effectively treating diabetes mellitus.

Peptic ulcer is a disorder of the upper gastrointestinal tract that is caused by gastric acid. There are various chemical agents available for the treatment of peptic ulcers, but claim serious side effects. Herbal drugs are preferred over chemical agents due to their relatively less toxicity, better acceptability and better compatibility with human body. Lesser adverse effects, economical, effective and easy availability. The present research has been carried out to investigate antiulcer activity of Hydroalcoholic leaf extract of Pisonia grandis R.Br (HEPG) using Indomethacin induced gastric ulcer and Pylorus ligation induced gastric ulcer in wistar rats. Ulcer score, ulcer index and number of ulcers were determined for indomethacin and pylorus ligation induced gastric ulcers. Antiulcer effect of Pisonia grandis R.Br (HEPG) was compared with standard drug omepprazole (20mg/kg). These observations helped us to conclude that Hydroalcoholic leaf extract of Pisonia grandis R.Br had significant antiulcer properties.

Purpose To provide commentary and points of caution to consider before incorporating data mining as a routine component of any Pharmacovigilance program, and to stimulate further research aimed at better defining the predictive value of these new tools as well as their incremental value as an adjunct to traditional methods of post-marketing surveillance.

A novel is ligand namely 5,5'-(6-(4-methoxyphenoxy)-1,3,5-triazine-2,4-diyl)bis (azanediyl)diquinolin-8-ol (PBDQ-6)  has been prepared and characterized. This ligand was characterized by IR, 1H-NMR, and elemental analysis. Coordination polymers of this bis-ligand (NBDQ) were prepared with Cu(II), Ni(II), Co(II), Mn(II), and Zn(II) metal ions. All of these coordination polymers were characterized by elemental analyses, IR spectral and diffuse reflectance spectral studies. The thermal stability was evaluated by thermo gravimetric analyses (TGA). In addition, all of the coordination polymers have been characterized by their magnetic susceptibilities. All the novel synthesized compounds were screened for their antibacterial and antifungal activities.

Relative Reporting Ratio calculation: Reports involving Varenicline (all trade names) 1673 (0.05 %) Reports involving MedDRA term "Suicidal behavior": 105 (0.003 %) Expected number of reports if independent: 1673 * 105 / 3130922 = 0.056 Relative reporting ratio (RR): N / E = 5 / 0.056 = 89.29 FDA MedWatch

Results from clinical trials and clinical practice have shown statins to be generally well tolerated with a low frequency of clinically relevant side effects. Nevertheless, there are rare occasions when adverse events (AEs), sometimes serious, may occur. Rosuvastatin is the newest statin to be approved in the USA and many other countries. As part of the continued assessment of the benefit-risk profile of rosuvastatin, AstraZeneca has developed a progressive, comprehensive pharmacoepidemiology programme to complement safety data obtained from randomised clinical trials and spontaneous reporting systems, which have demonstrated that rosuvastatin has a safety profile in line with comparator statins. This programme comprises nine studies conducted in recognised centres of excellence assessing over 50 000 patients treated with rosuvastatin. It consists of three components: patient characteristics studies (four studies), safety evaluation studies (four studies); and review of data generated from the Prescription-Event Monitoring (PEM) study, designed and run by an independent third party. Patient characteristics studies are designed to describe the characteristics and drug utilisation patterns of new users of rosuvastatin compared with new users of other statins in automated databases. Safety evaluation studies will examine the rates of specific AEs in different cohorts of statin users and determine risk factors for these events using data recorded prospectively in automated databases with case adjudication via medical record review. The independent PEM study will monitor any significant events recorded by general practitioners since starting rosuvastatin treatment. This article is an overview of the rationale and methodology of the rosuvastatin pharmacoepidemiology programme.

a Medical and clinical pharmacology laboratory, pharmacoepidemiology unit, EA 3696, IFR Inserm 126, Paul-Sabatier university, school of medicine, Toulouse, France b Clinical pharmacology department, Midi-Pyrénées center for pharmacovigilance, pharmacoepidemiology, and drug information, Toulouse teaching hospital,

Transfer of automated laboratory data collected during routine clinical care from the laboratory information system into a database format that enables linkage to other administrative (e.g., patient characteristics) or clinical (e.g., medication, diagnoses, procedures) data provides a valuable tool for clinical epidemiological research. It allows the investigation of biochemical characteristics of diseases, therapeutic effects and diagnostic and/or prognostic markers for disease with easy access and at relatively low cost. To this end, the Utrecht Patient Oriented Database (UPOD), an infrastructure of relational databases comprising data on patient characteristics, laboratory test results, medication orders, hospital discharge diagnoses and medical procedures for all patients treated at the University Medical Centre Utrecht since January 2004, was established. Current research within UPOD is focused on the innovative linkage of laboratory and medication data, which, for example, makes it possible to assess the quality of pharmacotherapy in clinical practice, to investigate interference between laboratory tests and drugs, to study the risk of adverse drug reactions, and to develop diagnostic and prognostic markers or algorithms for adverse drug reactions. Although recently established, we believe that UPOD broadens the opportunities for clinical pharmacoepidemiological research and can

A  simple,  fast  and  accurate  method  has  been  developed  for  the  estimation of  benzene content  in  Lovastatin  by  Gas  Chromatography.  The analysis was carried out on Perkin Elmer Clarus 600 GC-HS Chromatograph. The column used was DB-624 30m X 0.32 mm X 1.8 µm fused silica analytical column (6%  cyanopropylphenyl  94 %  dimethylpolysiloxane  as  a stationary  phase).The  detector  used  was  FID  detector.

Carvedilol is an antihypertensive drug use for management of Hypertension. It has the half-life of 6 hr and oral bioavailability of 25% due to first pass metabolism. The total daily dose of Carvedilol is 25 mg, hence it required frequent dosing. Transdermal patches of Carvedilol were prepared for sustained release and improve bioavailability of drug and patient compliance. Different formulations were prepared by varying the amount of HPMC-K4M and Eudragit RS-100 by solvent casting method. The prepared formulations were evaluated for various parameters like thickness, tensile strength, folding endurance, % elongation, % moisture content, % moisture uptake, % drug content, In-vitro drug release, In-vitro permeation and skin irritation study. A 32 full factorial design was applied to check the effect of varying the amount of Eudragit-RS 100 (X1) and amount of HPMC-K4M (X2) on the responses i.e. tensile strength and percentage drug released in 20 hr (Q20) as dependent variables. Regression analysis and analysis of variance were performed for dependent variables. In-vitro release data were fitted to various models to ascertain kinetic of drug release. The best selected formulation is subjected to in-vitro skin permeation and skin irritation study. Batch F7 was considered optimum batch which contained 400 mg of Eudragit RS-100 and 600 mg of HPMC-K4M, showed release 95.73% up to 24 hr and was more similar to Zero order release kinetics (r2=0.982). Batch F7 showed flux of 125.8 μg/cm2/h, hence the patch area of 1.33 cm2 would be expected to deliver targeted flux of 83.72μg/cm2/h.

A new simple, accurate, precise and reproducible Ion chromatography method has been developed for the estimation of Methane sulfonic acid in Busulfan injectable dosage. The method which is developed is also validated in complete compliance with the current regulatory guidelines by using well developed analytical method validation techniques and tools which comprises with the analytical method validation parameters like Linearity, LOD and LOQ determination, Accuracy, Method precision, Specificity, System suitability, Robustness, Ruggedness etc. by adopting the current method the linearity obtained is near to 0.999 and thus this shows that the method is capable to give a good detector response, the recovery calculated was within the range of 85% to 115% of the specification limits.

The purpose of this study was to evaluate the possibility of taste masking of Levocetirizine dihydrochloride (L-CTZ) by means of inclusion complexation and ion exchange resin. Initially an attempt was given to mask the bitter taste of the drug by inclusion complexation with β-Cyclodextrin using kneading method. But from gustatory evaluation, it was found that β-Cyclodextrin was not proven good for effective taste masking. So, another attempt was given to mask bitter taste of Levocetrizine diHCl by Kyron T-114 (weak cation exchange resin). It is a water-insoluble, high molecular weight, cross linked polymer of methacrylic acid. Kyron T-114 is inexpensive and this method is simple, rapid and cost-effective method for taste masking. Ion exchange resin complex was prepared by the batch technique and various parameters viz. resin activation, drug: resin ratio, pH, temperature, swelling time and stirring time were optimized to successfully formulate the tasteless Drug Resin Complex (DRC). Maximum drug loading was obtained when the resin was activated by acid treatment, with 1:3 drug: resin ratio, soaked in water for 90 min. and stirred with the drug for 240 minutes, pH maintained 5.5 and temperature maintained 30áµ’C. Complexation was confirmed by FT-IR and DSC study. The drug resin complex was evaluated for taste in-vitro and in-vivo evaluation. The volunteers rated the complexes as tasteless and agreeable. Drug release from DRC in salivary pH was insufficient to impart bitter taste. Complete drug release was observed at gastric 0.1 N HCl (pH 1.2). Formulation of drug resin complex was confirmed by FT-IR and DSC studies.

The objective of present study was to develop pharmaceutically elegant and stable enteric coated tablet formulation for highly unstable drug in acidic environment using pH dependent polymers. Omeprazole is a specific and non-competitive inhibitor of the enzyme H+/K+-ATPase. It is unstable in conditions of low pH and required protection from the effects of gastric acid when given orally so it is formulated in the form of enteric coated dosage forms. The core tablets were prepared by direct compression method using different concentration of crospovidone as a super disintegrant. Formulations showing less disintegration time were first subcoated with HPMC 15 cps upto 3% weight gain, followed by enteric coating with Eudragit L 100, Eudragit L 100-55 and Cellulose acetate phthalate. Pre and post compression evaluation of core and coated tablets were carried out. In vitro drug release studies were conducted in acidic and basic media to determine the appropriate coating ratio. All batches enteric coated with 8% weight gain of three polymers showed stable coating in 0.1 N HCl for 2 hours. Formulated batch F11 with 7% weight gain of Eudragit L 100-55 showed stable coating in 0.1 N HCl and had shown complete drug release in phosphate buffer pH 6.8. The prepared enteric coated tablets exhibited good physical and chemical stability, when subjected to accelerated stability studies. Further, when compared to marketed formulation (OPT tablet 20 mg Omeprazole), the prepared enteric coated tablets showed excellent similarities with marketed product (with respect to drug content, disintegration time and drug release) thereby establishing bioequivalence with marketed product.

Impurity profiling is the process of acquiring and evaluating data that establishes biological safety of an individual impurity. Impurity is considered as any other organic material, besides the drug substance, or ingredients, arise out of synthesis or unwanted chemicals that remains with API’s. The control of impurities is currently a critical issue to the pharmaceutical industry. International Conference on Harmonization (ICH) formulated guidelines regarding the control of impurities. Various regulatory authorities like ICH, USFDA, Canadian Drug and Health Agency are emphasizing on the purity requirements and the identification of impurities in Active Pharmaceutical Ingredient’s (API’s). Identification of impurities is done by TLC, HPLC, The advent of hyphenated techniques has revolutionized impurity profiling, by not only separation but structural elucidation of impurities as well. The most exploited techniques, for impurity profiling of drugs are LC-MS-MS, LC-NMR, LC-NMR- MS, GC-MS, and LC-MS.

A straightforward, efficient and more sustainable solvent-free method has been developed for the synthesis of benzimidazole derivatives to achieve yields that were comparable to or better than, those in conventional media. It is noteworthy that the reaction was exclusively carried out in Zinc chloride catalysis system, rendering the methodology highly valuable from both environment and economic points of view. The various benzimidazoles were synthesized by the reaction of o-phenylenediamine with different types of aldehydes and characterized by their Physical constant, FT-IR Spectra, 1H NMR Spectra and LCMS. The excellent chemo selectivity, mild reaction condition, short reaction times and excellent yield made the best method then other methods.

An accurate, precise, simple and economical High Performance Liquid Chromatographic method for the Estimation of Bortezomib in its lyophilized dosage form has been developed. The method developed is Reverse Phase High Performance Liquid Chromatographic method using Hypersil BDS C18 column (Length: 150 mm, Diameter: 4.6mm, Particle size: 5μ) with a simple 0.1 % TFA buffer and Acetonitrile mixed in the proportion of 20:80v/v as a mobile phase, and Methanol: Water (90:10) as a diluent. The method so developed was validated in compliance with the regulatory guidelines by using well developed analytical method validation tool which comprises with the analytical method validation parameters like Linearity, Accuracy, Method precision, Specificity with forced degradation, System suitability, Robustness and Ruggedness. The results obtained were well within the acceptance criteria.

Rapid microbiological method technologies aim to provide more sensitive, accurate, precise, and reproducible test results when compared with conventional, growth-based methods. Rapid methods normally involve some form of automation and the methods often capture data electronically. With several different technologies available on the marketplace, the microbiologist has a difficult, and sometimes expensive, choice to make in selecting the optimal method. This article outlines some of the considerations that need to be considered for their selection.

Quality by Design (QbD) refers to a holistic approach towards drug development. The purpose of research was to implement quality by design to study prospective process validation of 4 mg Salbutamol Sulphate Tablets with risk-based approach. Validation is one of the important steps in achieving and maintaining the quality of the final product. Quality Target Product Profile, Critical Quality Attributes, Critical Process Parameters, Design Space and control strategy are identified with the help of Quality Risk Management. Three initial batches of same size, method, equipment was taken for process validation. The critical parameters involved in sifting, dry mixing, preparation of granulating solution, wet mixing, drying, sizing, lubrication, compression were identified and evaluated. The formulation properties of three initial batches of process validated tablets are compared with the marketed products of Salbutamol Sulphate Tablets (Astahlin tab and Salbetol tab). Results obtained with this process validation data provides high degree of assurance that manufacturing process produces product meeting its predetermined specifications and quality attributes. The output of process validation can be used to increase productivity, its consistent quality and decreasing the need for processing and market complaints.

Herbal drugs are traditional method of treating the disease in the world wide, the plant having ability to treat the disease is known as medicinal plants. Several types of medicinal plants are exists in the nature and effective in different type of disease. Peptic ulcers are a broad term that includes ulcers of digestive tract in the stomach or the duodenum. The formation of peptic ulcers depends on the presence of acid and peptic activity in gastric juice plus a breakdown in mucosal defenses. There are two major factors that can disrupt the mucosal resistance to injury: non-steroidal anti-inflammatory drugs (NSAIDs) example, aspirin and Helicobacter pylori infection. Numerous natural products have been evaluated as therapeutics for the treatment of a variety of diseases, including peptic ulcer. This article reviews the anti-acid/anti-peptic, gastro-protective and/or antiulcer properties of the most commonly employed herbal medicines. This article will be concerned only the pharmacology of that plant which shows the antiulcer and gastro-protective effects and among all the plants which one is more potent for anti-ulcer activity.

Ziziphus oenoplia Linn., Mill, is a commonly occurring thorny shrub found to have many uses such as anthelmintic, antiseptic, hepatoprotective, stomachalgia, digestive etc. It is also used in ascaris infection and healing of wounds. The plant is reported to possess alkaloids, tannins and carbohydrates. Alkaloids have also been reported to posses many biological activities like anticancer, hepatoprotective, antihelmintic etc. Therefore, this plant offers much scope to investigators on different perspectives such as Pharmacognosy, Phytochemistry and Pharmacology. The following studies highlight the botanical as well as phytochemical constituents, macroscopic, microscopic and preliminary studies of roots. These observations will help in the botanical identification and the standardization of drug in crude form and also to distinguish the drug from its adulterants. Hopefully, this little work will help to inform the people who are not aware of the plant Ziziphus oenoplia Linn., mill (Rhamnaceae) which has multi-farious beneficial properties for medicine, agriculture and husbandry.

Aceclofenac is non-steroidal anti-inflammatory drug with marked anti-inflammatory and analgesic properties. It is indicated for the relief of pain and inflammation in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Aceclofenac is BCS class II drug with low solubility and high permeability. Micronization technique is used to increase the solubility and thus dissolution of Aceclofenac. The micronization was done using jet mill micronizer. The initial particle size of drug is 297.33 µ (D90) which was reduced to particle size 121.87 µ (D90) with single micronization, particle size 116.08 µ (D90) with double micronization and 89.23 µ (D90) with triple micronization of drug. It was observed that the solubility and thus dissolution of Aceclofenac was increased in principle media of 6.8 phosphate buffer and discriminating media 4.5 Acetate buffer with single, double and triple micronization. Thus, it can be justified that micronization is one of the good technique for enhancement of solubility of Aceclofenac by reduction of particle size of drug.

This paper reviews constructed drug delivery systems applying osmotic principles for controlled drug release from the formulation. Osmotic devices which are tablets coated with walls of controlled porosity are the most promising strategy based systems for controlled drug delivery. In contrast to common tablets, these pumps provide constant (zero order) drug release rate. When these systems are exposed to water, low levels of water soluble additive is leached from polymeric material i.e. semipermeable membrane and drug releases in a controlled manner over an extended period of time. The main clinical benefits of oral osmotic drug delivery system are their ability to improve treatment tolerability and patient compliance. These advantages are mainly driven by the capacity to deliver drugs in a sustained manner, independent of the drug chemical properties, of the patient’s physiological factors or following food intake. This review brings out the theoretical concept of drug delivery, history, advantages and disadvantages of the delivery systems, types of oral osmotic drug delivery systems, factors affecting the drug delivery system and marketed products.

Un panorama introductorio de farmacovigilancia y farmacoepidemiología dirigido a médicos clínicos y a profesionales de la salud, con la colaboracion de Marie Lindquist, Judith K. Jones, Ronald Meyboom, Inés Bignone, Elki Sollenbring, Geoffrey Bowring. Editado por Raquel Herrera Comoglio y Luis Alesso en colaboración con el Uppsala Monitoring Centre
Prólogo
Marie Lindquist
Introducción
Luis Alesso, Raquel Herrera Comoglio
La Farmacovigilancia en el proceso de seguridad de los medicamentos
Raquel Herrera Comoglio, Luis Alesso
Monitorización espontánea: pasado y futuro
Ronald Meyboom
Algunos casos en la historia de la Farmacovigilancia
Raquel Herrera Comoglio
Reacciones adversas a medicamentos
Raquel Herrera Comoglio, Luis Alesso
Evaluación de la causalidad en farmacovigilancia
Luis Alesso, Raquel Herrera Comoglio
Marie Lindquist
Detección de la señal en farmacovigilancia
Luis Alesso, Raquel Herrera Comoglio, Inés Bignone
Detección y verificación de problemas de seguridad de medicamentos
Raquel Herrera Comoglio, Judith K. Jones
El Programa Internacional de Farmacovigilancia de la Organización Mundial de la Salud
Elki Sollenbring, Geoffrey Bowring

Prólogo
Marie Lindquist
Interacciones farmacológicas
Raquel Herrera Comoglio, Luis Alesso, Pedro Saúl Lipszyc
Interacciones de especial importancia clínica
Raquel Herrera Comoglio, Marcelo Luis Ponte
Reacciones adversas a medicamentos
por hipersensibilidad
Raquel Herrera Comoglio, María Teresa Serra Criscuolo
Reacciones adversas a medicamentos y farmacogenética
Raquel Herrera Comoglio
Prolongación del intervalo Q-T inducido por fármacos
Guillermo Di Girolamo, Guillermo A. Keller
Biodisponibilidad y bioequivalencia
Ricardo Bolaños
La farmacovigilancia en Argentina:
situación actual y lineamientos para el futuro
Inés Bignone
El Sistema Nacional de Farmacovigilancia
en Argentina
Viviana G. Bologna
Problemas de calidad de medicamentos
en Argentina
María Beatriz Cardoso
Comunicación en Farmacovigilancia
Bruce Hugman

postmarketing or post-authorisation period, with due attention directed towards pre-clinical safety data, clinical trials and adverse events. As the biological sciences have evolved, pharmacovigilance has slowly shifted toward earlier, proactive consideration of risks and potential benefits of drugs in the pre-and peri-approval stages of drug development, leading to a maturing of drug safety risk management. Further advances in biology, pharmacology and improvements in computational applications to medicine have led to the development of more complex medicines previously unobtainable and have also permitted a more thorough assessment of risks and potential benefits even earlier in the development process. Elevated public concern with the safety of more sophisticated medicines, combined with new science, have led pharmaceutical innovators, regulators and healthcare professionals to collaborate to develop guidelines, which drive enhanced pharmacovigilance and safety risk management earlier in drug development.

The present study was designed to analyze the various phytoconstituents present in different extracts of seeds of Calotropis gigantea. Extracts of seeds of C. gigantea were prepared in different solvents viz. methanol, chloroform, petroleum ether, di-ethyl ether and water. The screening was performed for alkaloids, anthraquinones, flavonoids, saponins, tannins, and glycosides. The color intensity or the precipitate formation was used as analytical responses to these tests. The phytochemical tests revealed the presence of alkaloids, glycosides, flavonoids, tannins, saponins, carbohydrates, fixed oils and fats.

Los capítulos presentan las principales causas de efectos adversos:
Interacciones, hipersensibilidad, farmacogenética, prolongación del intervalo Q-T, temas de calidad de medicamentos, bioequivalencia, notificaciones en Argentina y aspectos prácticos para comunicación
en farmacovigilancia.
Editado por Raquel Herrera Comoglio y Luis Alesso, en colaboración con el Uppsala Monitoring Centre.
Prólogo
Marie Lindquist
Introducción
Luis Alesso, Raquel Herrera Comoglio
Interacciones farmacológicas
Raquel Herrera Comoglio, Luis Alesso, Pedro Saúl Lipszyc
Interacciones de especial importancia clínica
Raquel Herrera Comoglio, Marcelo Luis Ponte
Reacciones adversas a medicamentos
por hipersensibilidad
Raquel Herrera Comoglio, María Teresa Serra Criscuolo
Reacciones adversas a medicamentos y farmacogenética
Raquel Herrera Comoglio
Prolongación del intervalo Q-T inducido por fármacos
Guillermo Di Girolamo, Guillermo A. Keller
Biodisponibilidad y bioequivalencia
Ricardo Bolaños
La farmacovigilancia en Argentina:
situación actual y lineamientos para el futuro
Inés Bignone
El Sistema Nacional de Farmacovigilancia
en Argentina
Viviana G. Bologna
Problemas de calidad de medicamentos
en Argentina
María Beatriz Cardoso
Comunicación en Farmacovigilancia
Bruce Hugman

To estimate the prevalence of attention deficit hyperactivity disorder (ADHD) pharmacological treatment, and its demographic and clinical details, and to estimate the proportion of patients in the target group who stopped ADHD treatment and investigate possible factors for continuation or cessation of treatment. A pharmacoepidemiological study using an automated database and a qualititative study using patient interviews. Part 1 was a pharmacoepidemiological study that provided accurate data on use and cessation of ADHD drugs. Part 2 was an in-depth interview study to investigate the reasons, processes and outcomes of treatment cessation. Part 1: primary care using the General Practice Research Database (GPRD). Part 2: secondary and tertiary care paediatric clinics, child and adolescent mental health and adult mental health clinics in London, Nottingham, Dundee and Liverpool. Part 1: patients were 15-21 years old during the study period (1 January 2001 and 31 December 2004), had at ...

Process analytical technology (PAT) involves the use of different technologies and tools to build quality into the products. Effective PAT implementation comprise of science-based understanding of the physical, chemical and mechanical properties of all elements of the proposed drug product. The overall PAT venture is promising for delivering an integrated systems approach for quality design, process analysis, understanding and control, continuous improvement, knowledge and risk-based management. The incorporation of early PAT devices, increase process efficiency and safety by acting on data in real time and by eliminating sampling. PAT applications, increase detailed knowledge of processes, leading to increased robustness and greater processing opportunities. Modern developments in analytical technologies provide chemical and analytical insights for all types of chemical reactions and process monitoring such as drying, distillations, crystallizations, hydrogenations, and others.

Multiple emulsions are also known as emulsions of emulsions, liquid membrane system or double emulsion. Multiple emulsions are polydispersed systems where both oil in water & water in oil emulsions exist simultaneously. This review focuses on preparation, characterization and potential applications of multiple emulsions. Multiple emulsions can be classified as water-in oil-in water (W/O/W) or oil-in-water-in-oil (O/W/O) emulsions. This review described five methods to prepare multiple emulsions viz. two-step emulsification method, modified two-step emulsification method, phase inversion method, membrane emulsification & micro channel emulsification method. The Multiple emulsion is characterized by average globule size & size distribution, area of interfaces, number of globules, rheological evaluation, zeta potential, percentage drug entrapment, In-vitro drug release. Multiple emulsions have been proposed to have numerous uses including their use as prolonged drug delivery system.

The aim of this investigation was to prepare orodispersible tablets of baclofen using various concentrations of superdisintegrant agents like Ac-Di-Sol, crospovidone, sodium starch glycolate by direct compression method. Nine formulations having superdisintegrants at different concentration levels were prepared. These tablets were evaluated for drug content, weight variation, friability, hardness, wetting time and invitro disintegration time. Among the formulations tablets of batch F3 containing Ac-Di-Sol showed superior organoleptic properties along with excellent in-vitro disintegration time and drug release as compere to other formulations. It was concluded that superdisintegrants addition technique is a usuful method for preparing orodispersible tablets by direct compression method.

The objective of this article is to review the principles underlying the development and evaluation of mucoadhesive microspheres and the research work carried out on these systems. Mucoadhesion is a topic of current interest in the design of drug delivery systems. Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Mucoadhesive microspheres may be designed to enable a prolonged residence time at the site of application or absorption and facilitate an intimate contact with the underlying absorption surface and thus contribute to improved and/or better therapeutic performance of drugs. In recent years such mucoadhesive microspheres have been developed for oral, buccal, nasal, ocular, rectal and vaginal routes for either systemic or local effects. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and various mucoadhesive drug delivery systems.

The aim of the present work to evaluate the anticataract activity of aqueous extract of Asparagus racemosus root using in vitro model of goat lens. In the in vitro study, goat lenses were incubated in artificial aqueous humor containing 55 mM glucose (cataractogenesis) with aqueous extract of Asparagus racemosus root (AEAR) at different concentrations of 250 μg/ml and 500μg/ml at room temperature for 72 hours. Biochemical parameters studied in the lens were electrolytes (Na+, Ca+, and K+), total proteins, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and Catalase. Photographic evaluation was also done. AEAR significantly prevented the glucose induced changes in biochemical parameters like sodium, calcium, and potassium, total proteins, MDA, SOD, GSH and Catalase. Photographic evaluation also indicated that AEAR prevented the opacity of the lens compared to model control group in vitro. These results suggest that prevention of cataract by aqueous extract of Asparagus racemosus root may be through a mechanism involving free radical scavenging, preventing lipid peroxidation and direct antioxidative capacity.

Study Objective: To describe the comparative incidence of dipeptidyl peptidase-4 (DPP-4) inhibitors and pancreatic carcinoma as reportedly available in the FDA AERS database. To date, there is limited literature concerning regarding the association between DPP-4 inhibitors and pancreatic carcinoma. Our goal was to provide health care practitioners a general understanding of the drug-disease occurrence.
Design: Retrospective cohort study
Data Source: We used Empirica Signal software to query AERS from November 1968 to December 31, 2013. The software was used to calculate a disproportionality statistic, namely the Empirical Bayesian Geometric Mean (EBGM), for reports of dipeptidyl peptidase-4 (DPP-4) inhibitors -associated pancreatic carcinoma. The FDA considers an EBGM significant if the 5th percentile of the distribution is at least two (EB05 > 2.0). With use of a disproportionality analysis, dipeptidyl peptidase-4 (DPP-4) inhibitors was compared with all agents listed in AERS.
Measurements and Main Results: One hundred fifty six patients who experience pancreatic carcinoma while receiving dipeptidyl peptidase-4 (DPP-4) inhibitor therapy.  An EB05 of 10.3 was determined for sitagliptin compared to all other agents included in AERS. Based on the available data patient characteristics were: 44% males, average age of 70 y/o and average duration of treatment with sitagliptin of 460 days.  At the time of the report none of the reported cases recovered and of these there were 28 reported deaths within the sitagliptin patients.
Conclusion:  There appears to be a statistical association between dipeptidyl peptidase-4 (DPP-4) inhibitor use and pancreatic carcinoma. Causality cannot be inferred from the data provided. Additional clinical studies are needed to further explore this statistical association.