ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF ATOMOXETINE HYDROCHLORIDE USING RAPID HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC TECHNIQUE

Objective: A simple, novel, sensitive, rapid high-performance liquid chromatographic (RP-HPLC) method has been developed and validated for quantitative determination of atomoxetine HCl (ATH) in bulk and formulations.Methods: The chromatographic development was carried out on RP-HPLC. The column used as Xterra RP 18 (250 mm × 4.6 mm, 5 μ particle size), with mobile phase consisting of methanol: water 80:20 V/V. The flow rate was 1.0 mL/min and the effluents were monitored at 270 nm.Results: The retention time was found to be 5.350 min. The method was validated as per International Conference on Harmonization Guideline with respect to linearity, accuracy, precision, and robustness. The calibration curve was found to be linear over a range of 2–10 μg/mL with a regression coefficient of 0.9999. The method has proved high sensitivity and specificity.Conclusion: The results of the study showed that the proposed RP-HPLC method was simple, rapid, precise and accurate which is useful for the routine determination of ATH in bulk drug and in its pharmaceutical dosage form

Nootropics use in the workplace. Psychiatric and ethical aftermath towards the new frontier of bioengineering

OBJECTIVE: The authors have sought to expound upon and shed a light on the rise of nootropics, which have gradually taken on a more and more relevant role in workplaces and academic settings. MATERIALS AND METHODS: Multidisciplinary databases have been delved into by entering the following keys: "nootropics", "cognitive enhancement", "workplace", "productivity", "ethics", "bioengineering". In addition, a broad-ranging search has been undertaken on institutional websites in order to identify relevant analysis and recommendations issued by international institutions and agencies. Papers and reports have been independently pored over by each author. This search strategy has led to the identification of 988 sources but only 64 were considered appropriate for the purposes of the paper after being selected by at least 3 of the authors, independently. RESULTS: The notion of an artificially enhanced work performance - carried out by the 'superworker' - is particularly noteworthy and resonates with the conception of contemporary work on so many different levels: the rising need and demands for higher degrees of flexibility and productivity on the job, the implications of a '24/7' society, where more and more services are available at any time, the ever greater emphasis on entrepreneurial spirit, individual self-reliance and self-improvement, and last but not least, the impact of an ageing society on economic standards and performance. CONCLUSIONS: Moreover, it is worth mentioning that human enhancement technologies will predictably and increasingly go hand in hand with gene editing, bioengineering, cybernetics and nanotechnology. Applications are virtually boundless, and may ultimately affect all human traits (physical strength, endurance, vision, intelligence and even personality and mood)

Taste masked orodispersible tablet of atomoxetine hydrochloride

In the present work, orodispersible tablets of atomoxetine HCl were designed by preparing tasteless complexes of atomoxetine HCl with weak cation ion exchange resins (Kyron T 134). The ion exchange complex were prepared by the batch process using activated Kyron T 134 with a drug: resin ratios 1:1, 1:2, 1:3 and 1:4 (% w/w). IR analysis, assay content and decomplexation studies confirmed complex formation. It was found that maximum complexation of drug with resin was noted between pH range 5-7, while activation of ion exchange resin affects the percent drug loading. Drug release from drug: resin complex in salivary pH was insufficient to impart bitter taste. A study on super-disintegrants along with directly compressible diluents is studied and its effect on disintegration time and enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity and in vitro dispersion time. Based on in vitro disintegration time (approximately 30 s), formulations were tested for in vitro drug release pattern in 0.1N HCl.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Taste masked orodispersible tablet of atomoxetine hydrochloride

In the present work, orodispersible tablets of atomoxetine HCl were designed by preparing tasteless complexes of atomoxetine HCl with weak cation ion exchange resins (Kyron T 134). The ion exchange complex were prepared by the batch process using activated Kyron T 134 with a drug: resin ratios 1:1, 1:2, 1:3 and 1:4 (% w/w). IR analysis, assay content and decomplexation studies confirmed complex formation. It was found that maximum complexation of drug with resin was noted between pH range 5-7, while activation of ion exchange resin affects the percent drug loading. Drug release from drug: resin complex in salivary pH was insufficient to impart bitter taste. A study on super-disintegrants along with directly compressible diluents is studied and its effect on disintegration time and enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity and in vitro dispersion time. Based on in vitro disintegration time (approximately 30 s), formulations were tested for in vitro drug release pattern in 0.1N HCl.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Formulation and Evaluation of Transdermal Patch for Atomoxetine hydrochloride

The aim of this study was to develop transdermal patch of Atomoxetine hydrochloride which has good mechanical properties. The transdermal patches were preapared used solvent casting method. Different groups of films with drug were prepared using different amalgamations of polymers such as HPMC (various grades), Polyox303, Eudragit RL 100.Considering solubility of drug and polymer, the solvent system of water: ethanol was chosen.In-vitro release of drug substance was performed  using phosphate buffer solution (PBS) pH 7.4. Compatibility of drug with different excipient (drug: excipient in the ratio 1:1) was carried out using Fourier Transform Infra-Red Spectroscopy (FTIR). Evaluation test such as weight variation, content uniformity, drug content, folding endurance, thickness, in-vitro dissolution and in-vitro disintegration were done. The folding endurance of the all batches found less than 500 times.The percentages of drug distribution was found in between 72 to 100%.The formulation F4 containing a combination of HPMC and Eudragit showed maximum drug release of 95.26%. The method employed to prepare patches was capable of producing patches with almost uniform drug distribution. Stability studies were conducted as per ICH guidlines (40±2○C at 75±5% RH) for optimized formulations and was found to be stable. Keywords: Atomoxetine hydrochloride, Transdermal Patc

Attention deficit hyperactivity disorder - symptoms, diagnosis and therapy among children and adults.

Introduction: The prevalence of Attention Deficit Hyperactivity Disorder (ADHD) in the world is estimated at about 5%. Among adults, it occurs with a frequency of 2.5%. This syndrome can significantly impair functioning in various areas of life. There is a treatment to reduce the symptoms. Aim of the study: The aim of the study was to collect and analyze publications on attention deficit hyperactivity disorder - symptoms, diagnosis and therapy, taking into account the differences among children and adults. Material and methods: We reviewed the literature available in the PubMed database using the keywords: "ADHD"; "Attention deficit hyperactivity disorder"; '' ADHD diagnosis', ''ADHD therapy'; ‘’ADHD drug therapy’, ‘’Methylphenidate’, ‘’Atomoxetine” Results: The clinical presentation of the disorder changes over the years. The main symptoms among children are related to inattention and impulsiveness, while among adults, hyperactivity can turn into a feeling of inner fear. Among children, frequent accompanying disorders are behavioral and oppositional-defiant disorders, and among adults, sleep disorders, personality, mood and anxiety disorders. ADHD treatment is based on a multimodal approach that uses cognitive behavioral therapy and effective stimulants (methylphenidate) and non-stimulants (atomoxetine) among children and adults. Conclusions: There are differences in symptoms, comorbidities and diagnosis of ADHD among children and adults. Pharmacotherapy is carried out using the same drugs that are safe and effective. Diagnosis of the disorder and both non-pharmacological and pharmacological help are important due to the risk of increased mortality in patients

Conocimiento enfermero en la farmacología del TDAH

Introducción: El trastorno por déficit de atención e hiperactividad (TDAH) es un trastorno que afecta a un 5 % de los adolescentes y entre un 2,5-4 % de los adultos, teniendo un gran impacto social. El objetivo principal de esta revisión es mostrar cuáles son los principales tratamientos para el TDAH, priorizando un orden de elección. Metodología: Se realizó una revisión de la literatura, escogiendo ensayos clínicos y revisiones sistemáticas sobre el tratamiento farmacológico del TDAH y los efectos secundarios asociados. Para ello, se realizó la búsqueda empleando los Descriptores en Ciencias de la Salud (DeCS) y los Medical Subject Headings (MeSH) en las siguientes bases de datos: PubMed, Cochrane y Scopus. Resultados: Se incluyeron 10 estudios que realizan una evaluación económica completa y de seguridad sobre el metilfenidato (MPH), las anfetaminas, entre ellas principalmente la lisdexanfetamina (LDX), y la atomoxetina (ATX). Conclusión: El tratamiento idóneo sería el MPH, puesto que cuenta con más ensayos sobre su seguridad y efectividad. Sin dejar de contemplar la LDX, que ha demostrado ser ligeramente superior al MPH en relación costeefectividad; pero, al ser más nueva, no cuenta con la misma evidencia que el MPH. Además, sería importante, tal y como reflejan los autores, un control exhaustivo de los tratados con estas sustancias que padezcan de patologías cardiovasculares, sobre todo en sus efectos a largo plazo, donde no encontramos suficiente literatura.Introduction: Attention deficit hyperactivity disorder (ADHD) is a disorder that affects 5% of adolescents and 2.5-4% of adults, having a big social impact. The primary objective is to know the main treatments for ADHD, prioritizing an order of choice. Methodology: An integrative review was carried out, choosing: clinical trials and systematic reviews about ADHD, drug treatments and its adverse effects. The literature search was done with Medical Subject Headings and Health Science Descriptors in different databases (PubMed, Cochrane and Scopus). Results: We include 10 studies conducting a comprehensive and safety assessment of methylphenidate (MPH), amphetamines, including mainly the lisdexamfetamine (LDX), and atomoxetine (ATX). Conclusion: The ideal treatment would be MPH, as it has more tests on its safety and effectiveness. While contemplating LDX, which has been shown to be slightly higher than MPH in cost-effectiveness; but, as it is more recent, it does not have the same evidence as the MPH. In addition, exhaustive control of those treated with these substances and suffering from cardiovascular pathologies would be important, especially in its long-term effects where we do not find enough literature

Розробка УФ-спектрофотометричного та екстракційно-спектрофотометричного методів кількісного визначення атомоксетину, придатних для хіміко-токсикологічного аналізу

The acute and lethal antidepressant poisonings have the tendency to grow, therefore, development of the methods for its chemical and toxicological analysis is a topical issue.Aim. To develop and validate the methods for the quantitative determination of atomoxetine, an antidepressant, using available and widely spread methods in the chemical and toxicological analysis practice, such as UV spectrophotometry and extraction-spectrophotometry in the visible region of the spectrum with methyl orange, an acidic azo dye.Materials and methods. Absorbance values of the solutions in the UV and visible regions of the spectrum were measured on a SF-46 spectrophotometer (LOMO), the spectral measurement range was from 190 to 1100 nm. The standard solution of atomoxetine in 0.1 M hydrocloric acid (300 μg/ml) was used for the UV spectrophotometric study, and the standard solution of atomoxetine in water (150 μg/ml) was used for the extraction spectrophotometry in the visible region.Results and discussion. The calibration curve for the UV spectrophotometric method was described by the equation of y = (0.00455 ± 4 · 10-5)x + (0.016 ± 0.005); linearity was observed within the atomoxetine concentration range of 15.0-210 μg/ml; LOD and LOQ were 1.8 μg/ml and 5.6 μg/ml, respectively. The calibration curve for the extraction spectrophotometric method was described by the equation of y = (0.00808 ± 5 · 10-5)x; linearity was observed within the atomoxetine concentrations of 15.0-150.0 μg in a sample; LOD and LOQ were 1.4 μg and 4.3 μg in a sample, respectively.Conclusions. The methods developed for the quantitative determination of atomoxetine using the UV-spectrophotometric method and extraction spectrophotometry in the visible region of the spectrum satisfy the requirements set to the methods recommended for use in the forensic toxicology, and it has been confirmed by the validation characteristics.Количество острых и летальных отравлений лекарственными препаратами антидепрессивного действия имеет тенденцию к росту, что делает актуальным разработку методов их химико-токсикологического анализа.Целью данных исследований является разработка и валидация методик количественного определения антидепрессанта атомоксетина с помощью доступных и широко внедренных в практику химико-токсикологического анализа методов УФ-спектрофотометрии и экстракционной спектрофотометрии в видимой области спектра с кислотным азокрасителем метиловым оранжевым.Материалы и методы. Светопоглощение растворов в УФ- и видимой областях спектра измеряли на спектрофотометре СФ-46 (ЛОМО), спектральный диапазон измерений – от 190 до 1100 нм. Использовали стандартный раствор атомоксетина в 0,1 М кислоте хлоридной (300 мкг/мл) для УФ-спектрофотометрических исследований и стандартный раствор атомоксетина в воде (150 мкг/мл) для исследований методом экстракционной спектрофотометрии в видимой области.Результаты и их обсуждение. Калибровочный график для УФ-спектрофотометрического метода описывался уравнением: y = (0,00455 ± 4 · 10-5)x + (0,016 ± 0,005); линейность наблюдали в пределах концентраций атомоксетина 15,0-210 мкг/мл; LOD и LOQ составили, соответственно, 1,8 мкг/мл и 5,6 мкг/мл. Калибровочный график для экстракционно-спектрофотометрического метода описывался уравнением: y = (0,00808 ± 5 · 10-5)x; линейность наблюдали в пределах концентраций атомоксетина 15,0-150,0 мкг в пробе; LOD и LOQ составили, соответственно, 1,4 мкг и 4,3 мкг в пробе. Выводы. Разработанные методики количественного определения атомоксетина с использованием УФ-спектрофотометрического метода и экстракционной спектрофотометрии в видимой области спектра удовлетворяют требованиям к методам, рекомендованным для использования в судебной токсикологии, что подтверждено валидационными характеристиками.Кількість гострих та летальних отруєнь лікарськими препаратами антидепресивної дії має тенденцію до зростання, що робить актуальним розробку методів їх хіміко-токсикологічного аналізу.Метою даних досліджень є розробка і валідація методик кількісного визначення антидепресанта атомоксетину за допомогою доступних та широко впроваджених у практику хіміко-токсикологічного аналізу методів УФ-спектрофотометрії та екстракційної спектрофотометрії у видимій області спектра з кислотним азобарвником метиловим оранжевим. Матеріали та методи. Світлопоглинання розчинів в УФ- та видимій областях спектра вимірювали на спектрофотометрі СФ-46 (ЛОМО), спектральний діапазон вимірювань – від 190 до 1100 нм. Використовували стандартний розчин атомоксетину в 0,1 М кислоті хлоридній (300 мкг/мл) для УФ-спектрофотометричних досліджень і стандартний розчин атомоксетину у воді (150 мкг/мл) для досліджень методом екстракційної спектрофотометрії у видимій області.Результати та їх обговорення. Калібрувальний графік для УФ-спектрофотометричного методу описувався рівнянням: y = (0,00455 ± 4 · 10-5)x + (0,016 ± 0,005); лінійність спостерігали в межах концентрацій атомоксетину 15,0-210 мкг/мл; LOD та LOQ становили, відповідно, 1,8 мкг/мл та 5,6 мкг/мл. Калібрувальний графік для екстракційно-спектрофотометричного методу описувався рівнянням: y = (0,00808 ± 5 · 10-5)x; лінійність спостерігали в межах концентрацій атомоксетину 15,0-150,0 мкг в пробі; LOD та LOQ становили, відповідно, 1,4 мкг та 4,3 мкг в пробі.Висновки. Розроблені методики кількісного визначення атомоксетину з використанням УФ-спектрофотометричного методу та екстракційної спектрофотометрії у видимій області спектра задовольняють вимогам щодо методів, рекомендованих для використання в судовій токсикології, що підтверджено валідаційними характеристиками

FORMULATION AND EVALUATION OF CHLOROTHALIDONE LOADED MOUTH DISSOLVING FILM-A BIOAVAILABILITY ENHANCEMENT APPROACH USING MULTILEVEL CATEGORIC DESIGN

Objective: The intension of the present study includes fabrication and optimization of mouth dissolving film loaded with Chlorothalidone by solvent evaporation techniques using two components and their three levels as multilevel Categoric design. Methods: Major problem associated with the development of film loaded with BCS class II drug is to increase its solubility. Here the Chlorothalidone solubility achieved by co-solvents, such as methanol. After dissolving the drug in co-solvent, this drug solution is poured into an aqueous dispersion of Hydroxypropyl Methylcellulose E5 (HPMC E5) and Polyethylene glycol 400 (PEG 400). The two independent variables selected are factor A (concentration of HPMC E5) and factor B (concentration of PEG 400) was selected on the basis of preliminary trials. The percentage drug release (R1), Disintegration time in sec (R2) and folding endurance (R3) were selected as dependent variables. Here HPMC E5 used as a film former, PEG 400 as plasticizer, mannitol as bulking agent, Sodium starch glycolate as a disintegrating agent, tween 80 as the surfactant, tartaric acid as saliva stimulating agent, sodium saccharin as a sweetener and orange flavour etc. These fabricated films were evaluated for physicochemical properties, disintegration time and In vitro drug release study. Results: The formulation F6 has more favorable responses as per multilevel categoric design is % drug release about 98.95 %, average disintegration time about 24.33 second and folding endurance is 117. Thus formulation F6 was preferred as an optimized formulation. Conclusion: The present formulation delivers medicament accurately with good therapeutic efficiency by oral administration, this mouth dissolving films having a rapid onset of action than conventional tablet formulations