Development and Validation of High-Performance Liquid Chromatography Method for the Quantification of Remdesivir in Intravenous Dosage Form.

Corona virus disease 2019 (COVID-19) has posed a mounting threat to public health with worldwide outbreak caused by a novel virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recently, remdesivir (RDV) has been approved by Food and Drug Administration (FDA) for treating COVID-19 patients ≥12 years old requiring hospitalization. To the best of our knowledge, a simple method to estimate RDV in the pharmaceutical formulations using high-performance liquid chromatography (HPLC) is still unexplored, highlighting the need for a precise analytical method for its quantification. The prime purpose of the current investigation was to develop and validate a well-grounded HPLC method for quantification of RDV in pharmaceutical formulations. The best chromatogram was obtained by means of an Inertsil ODS-3V column using a mobile phase of milli-Q water modified to pH 3.0 with o-phosphoric acid and acetonitrile (50:50, % v/v) at a flow rate of 1.2 mL/min and wavelength of detector set at 246 nm with retention time being achieved at 6.0 min. The method was validated following International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 (R1) guidelines for various parameters such as specificity and selectivity, system suitability, linearity, precision, accuracy, limits of detection and quantification, and robustness. The method developed for the quantification of RDV was found to be linear in the concentration range of 25-2,500 ng/mL with limit of detection and limit of quantification of 1.95 and 6.49 ng/mL, respectively. Assay value of 102% ± 1% was achieved for marketed injectable dosage form when estimated by the validated method. Therefore, in this study a simple, rapid, sensitive, selective, accurate, precise, and robust analytical method was developed and validated for the quantification of RDV using HPLC. The established method was successfully employed for quantification of RDV in marketed pharmaceutical formulation.

A comparative study of two separate analytical techniques for the simultaneous determination of diclofenac sodium and diacerein from combined dosage form

ABSTRACT Diclofenac sodium (DS) and diacerein (DC) have emerged as a potential combination therapy for the treatment of knee osteoarthritis. Therefore a validated analytical method is essential for the simultaneous estimation of both from combined dosage form. A ratio derivative spectrophotometric and a chromatographic technique have been developed for the simultaneous determination of DS and DC. The quantification was done at 263.00 nm for DC and 304.50 nm for DS in the first method, whereas 257 nm for DC and at 274 nm for DS for LC-DAD analysis in chromatographic method using acetate buffer and methanol as the mobile phase at a flow-rate 0.50 mL/min. Both of these methods are found to be linear in the concentration range under study with r2 value 0.999 and 0.996 for DS and DC respectively in ratio derivative spectroscopy and 0.998 and 0.999 for DS and DC respectively in LC-DAD study. Both of these methods are found to be accurate and precise, though greater robustness and precision is observed with chromatographic analysis over the ratio derivative spectroscopy. Statistically there was no significant difference between proposed ratio derivative spectrophotometric and LC-DAD methods.

[Criteria for good prescribing practice in children]. / Inhaltliche Kriterien für eine gute Verordnung bei Kindern.

Paediatric prescribing is complex. A whole range of aspects needs to be considered to achieve an efficacious and safe drug therapy for children. Legal requirements for prescribing are clearly insufficient for this purpose. Children are immature individuals under constant growth and development. Consequently, based on age and cognitive abilities of the child individual drugs and dosing regimens have to be chosen. Frequent off-label use and a lack of age-appropriate formulation worsen the situation. Additionally, not all dosage forms are similarly adequate in different age groups. Taste significantly influences patient adherence. Dose calculations based on body weight are prone to errors, putting a point on the wrong place or mixing up measuring units easily result in ten-fold dosing errors. Computer-based tools to enhance prescribing are promising but, however, not yet widely implemented in paediatrics because of missing evidence-based data sources and the hugely complex process. Communication between clinicians and pharmacists as well as with the patient remains very important.

Inappropriate crushing information on ward lists: cytotoxic drugs, capsules, and modified release formulations are gravely neglected.

PURPOSE: The aim of this study was to assess the quality of the information sources on the modification of solid medication dosage forms (crushing, suspending) used on the wards of a large university hospital in Germany. METHODS: We performed on-site visits of all 79 wards of the hospital and collected available sources of information on the modification of solid medication dosage forms. To evaluate the quality of such information, we gathered reference information for each listed brand from the respective pharmaceutical company, transferred this information to a knowledge base, and classified it into three categories, i.e., modification not allowed, modification allowed, and modification allowed under certain circumstances. RESULTS: Twenty-two lists of information on drug modification were identified in the 79 wards. Each list contained errors, and on average 17.0 % (range 8.0-32.3 %) of the brands listed had been withdrawn from the market or the information on crushing and/or suspending was inappropriate. Most of the incorrect information either concerned brands containing ingredients that were potentially hazardous to the staff members who prepared the drugs or referred to special dosage forms such as capsules and modified release formulations (e.g., cytotoxic drugs). CONCLUSION: We found that the lists posted on the wards were often outdated and did not take into account the limitations/problems of preparing drugs on the ward. Our results emphasize that lists posted in wards need to be checked regularly and that "ready-to-use" lists from third parties might require adaptation to site-specific conditions in order to protect healthcare staff from exposure to potentially hazardous drugs during drug preparation and ensure safe drug application to the patient.

Antioxidant activity evaluation of new dosage forms as vehicles for dehydrated vegetables.

A dehydrated vegetables mixture loaded in four pharmaceutical dosage forms as powder, effervescent granulate, sugar granulate and gumdrops were investigated for their antioxidant capacity using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging capacity assay, oxygen radical absorbance capacity assay and ferric reducing antioxidant potential assay. Total phenolic content of dehydrated vegetables powder mixture was also measured by the Folin-Ciocalteu method, so as to evaluate its contribution to their total antioxidant function. The effect of different temperatures on stability of these systems after 90 days storage was also evaluated. These formulations presented strong antioxidant properties and high phenolic content (279 mg gallic acid equivalent/g of sample) and thus could be potential rich sources of natural antioxidants. Antioxidant properties differed significantly among selected formulations (p < 0.05). Generally, the losses were lower in samples stored under refrigeration. To interpret the antioxidant properties a kinetic approach was performed. Degradation kinetics for the phenolic content and antioxidant capacity followed a zero-order function. Effervescent granulate was the formulation which underwent faster degradation. Contrary, sugar granulate and gumdrops were much more slowly. Time required to halve the initial amount of phenolic compounds was 589 ± 45 days for samples stored at 4 º C, and 312 ± 16 days for samples stored at room temperature. These developed dosage forms are new and innovative approach for vegetable intakes in population with special requirements providing an improvement in the administration of vegetables and fruits.

RP-HPLC method development and validation for estimation of rivaroxaban in pharmaceutical dosage forms

Rivaroxaban, an anti-clotting medication, acts at a crucial point in the blood-clotting process and stops the formation of blood clots. In this study, RP-HPLC method was developed for the determination of rivaroxaban in tablets (Xarelto® (10 mg)). Phenomenex Luna 5 µm C18 100 Å LC Column (250 x 4.6 mm) was used at 40 ºC. Isocratic elution was performed with ACN:Water (55:45 v/v) mixture. The flow rate was 1.2 mL min-1 and UV detection was at 249 nm. Internal standard (Caffeine) and rivaroxaban were eluted within 2.21 and 3.37 minutes, respectively. The developed method was validated according to the ICH guidelines and found to be linear within the range 0.005 - 40.0 µg mL-1. The method was accurate, precise, robust and rapid. Thus, it was applied successfully for the quality control assay of rivaroxaban in tablet dosage form.

Rivaroxabana, fármaco anticoagulante, atua em um ponto crucial no processo de coagulação do sangue e impede a formação de coágulos sanguíneos. Neste estudo, desenvolveu-se método de RP-HPLC para a determinação de rivaroxabana em comprimidos (Xarelto ® (10 mg)). Utilizou-se coluna LC (250 x 4,6 mm) Phenomenex Luna C18 5 mm 100 Å a 40 ºC. Realizou-se eluição isocrática com ACN: água (55:45 v/v). O fluxo foi de 1,2 mL min-1 e a detecção de UV foi a 249 nm. Padrão interno (cafeína) e rivaroxabana eluíram em 2,21 e 3,37 minutos, respectivamente. O método desenvolvido foi validado de acordo com as diretrizes do ICH e mostrou-se linear na faixa 0,005-40,0 mg mL-1. O método foi exato, preciso, robusto e rápido. Assim, foi aplicado com êxito para o ensaio de controle de qualidade da Rivaroxabana na forma de comprimidos.

Comparison of dissolution profile of extended-release oral dosage forms - two one-sided equivalence test

The aim of this work is to present the two one-sided test (TOST) as an alternative approach to compare dissolution profiles of extended-release dosage forms. The dissolution profiles of oxycodone extended-release tablets containing 10 mg, 20 mg and 40 mg (reference and generic) were evaluated according to the requirements described in United States Pharmacopeia. These dissolution profiles were compared using the conventional similarity factor (f2) and the proposed TOST as an equivalence test. TOST is a simple and alternative approach to compare dissolution profiles of extended-release dosage forms. It allows us to identify the time-point (or time-points) that did not show similarity. We concluded that the two one-sided test performed at a significance level of 5% and defined as D = 10 showed results comparable to those obtained by the conventional similarity factor (f2).

O objetivo deste trabalho é apresentar o teste uni-caudal duplo (TOST) como uma abordagem alternativa na comparação do perfil de dissolução de formas farmacêuticas de liberação prolongada. Os perfis de dissolução de comprimidos de liberação prolongada de oxicodona contendo 10 mg, 20 mg e 40 mg (genérico e referência) foram avaliados de acordo com os requisitos descritos na Farmacopeia Americana. Estes perfis de dissolução foram comparados empregando-se o fator de semelhança convencional (f2) e o método TOST como teste de equivalência. TOST é uma abordagem simples e alternativa para a comparação de perfis de dissolução de formas farmacêuticas de liberação prolongada. Este permite identificar o ponto (ou pontos) que não apresentou semelhança. Considerando-se D = 10, concluímos que o teste uni-caudal duplo num nível de significância de 5% apresenta resultados comparáveis àqueles obtidos com o fator de semelhança convencional (f2).

Protocolo de administración de medicamentos en enfermeria / Nursing protocol in drug administration

Entre los cuidados y diferentes actividades que realiza la enfermera, debe recorocerse que la administracion de medicamentos es una responsabilidad crucial, que no puede ser subestimada ya que los habitos poco cuidadosos y las distracciones pueden poner en peligro la vida de las personas. La falta de comunicacion entre los miembros del equipo de salud es una causa habitual de errores de medicacion. Al menos uno de cada 10 errores se deben al uso de nombres erroneos de medicamentos, confusiones en la dosificacion o falta de comprension de las abreviaturas.

Randomized phase II trial of weekly paclitaxel combined with carboplatin versus standard paclitaxel combined with carboplatin for elderly patients with advanced non-small-cell lung cancer.

BACKGROUND: The optimal platinum doublet regimen in elderly patients with non-small-cell lung cancer (NSCLC) is still uncertain. We conducted a randomized phase II study to compare the efficacy and safety of weekly paclitaxel combined with carboplatin with those of the standard schedule. PATIENTS AND METHODS: Elderly patients (age > or =70 years) with advanced NSCLC were randomly assigned to either the weekly arm {70 mg/m(2) paclitaxel on days 1, 8, and 15 and carboplatin [area under the curve (AUC) = 6] on day 1} or the standard arm [200 mg/m(2) paclitaxel and carboplatin (AUC = 6) on day 1]. The primary end point was the overall response rate (ORR). RESULTS: Eighty-two patients were enrolled. The ORR and median progression-free survival were 55% and 6.0 months for the weekly arm and 53% and 5.6 months for the standard arm. Grade 3/4 neutropenia and peripheral neuropathy were observed in 41% and 0% of the patients in the weekly arm and in 88% and 25% in the standard arm, respectively. CONCLUSIONS: This is the first randomized study that compares the platinum doublet designed specifically for the elderly. Regarding the safety, the weekly regimen was less toxic than the standard regimen and seems to be preferable for elderly patients with advanced NSCLC.

[Studies and reports of Chinese cut crude drugs dosage in clinical prescription of traditional Chinese medicine (section of surgery)].

OBJECTIVE: Study the actual dosage of clinical prescription in surgery of traditional Chinese medicine (TCM), and offer the consummate data for formulating the dosage standard of Chinese cut crude drug. METHOD: We made use of the methods of stratified sampling and random sampling to investigate 84,759 broth prescriptions of surgery of TCM in 21 various hospitals, 18 provinces, and constructed the database, then applied Weka KDD software to analyze. RESULT: We identified the frequency and clinical dosage intervals of 300 drugs, and the practical dosage of 155 drugs which dose has difference between in the actuality and in the pharmacopoeia. Most of drug's dosage centralized the four intervals: (3-6], (9-12], (12-15], (18-21], and the concrete dosage were 3, 6, 10, 12, 15, 20 g, etc. CONCLUSION: The dosages in the pharmacopoeia are not coincided with the practical dosages in surgery, and demand to revise. This paper will offer the consummate data for formulating the new dosage standard.

Differential electrolytic potentiometric determination of some thiol compounds in their dosage forms.

The application of direct current differential electrolytic potentiometry to an aqueous titration of L-cysteine hydrochloride, captopril and D-penicillamine has been investigated. The basic character of thiol compounds in nitric acid is enhanced to permit their direct titrations with silver nitrate. A pair of silver amalgam electrodes was used as an indicating system. Titration curve shapes obtained are almost symmetrical with sharp peaks. The optimum current density for those titrations was found to be 0.2-2 microA/cm2. The procedure was applied successfully to the determination of certain thiol compounds in drug formulations and the results were favorably compared statistically with those obtained from official methods.

Isolation and identification of cyclic imide and deamidation products in heat stressed pramlintide injection drug product.

This report summarizes the identification of six cyclic imide [Asu] and two deamidation products from a sample of pramlintide final drug product that had been stressed at 40 degrees C for 45 days. The pramlintide degradation products were isolated by cation exchange high-performance liquid chromatography (HPLC) followed by reversed-phase HPLC. The isolated components were characterized by mass spectrometry (MS), tandem MS (MS/MS) and when necessary, by enzymatic (thermolysin) digestion followed by liquid chromatography/mass spectrometry (LC/MS) and sequence analysis. The isolated products were identified as [Asu14]-pramlintide, [Asu21]-pramlintide, [Asu22]-pramlintide, [Asu35]-pramlintide, [1-21]-succinimide-pramlintide, and [1-22]-succinimide-pramlintide. Also identified were [Asp35]-pramlintide, the deamidation product of pramlintide at Asn35, and [Tyr37-OH]-pramlintide, the deamidation product of the pramlintide amidated C-terminal Tyr. Together these data support those presented earlier (C. Hekman et al., Isolation and identification of peptide degradation products of heat stressed pramlintide injection drug product. Pharm Res 1998;15:650-9) indicating that the primary mechanism of degradation for pramlintide in this pH 4.0 formulation is deamidation, with six of the eight possible deamidation sites observed to undergo deamidation. Gln-10 and Asn-31 are the only two residues subject to deamidation for which none is observed. The data indicate that the cyclic imide products account for approximately 20% of the total thermal degradation while the deamidation products account for 64%. The remaining degradation is due to peptide backbone hydrolysis.

Manejo de vía aérea en el área de emergencia: (intubación y drogas) / Airway management in the emergency area: (intubation and drugs)

Se evaluaron 42 pacientes politraumatizados que fueron atendidos en la emergencia y la unidad de politraumatizados del Hospital Dr. Domingo Luciani, que necesitaron de manejo de vía aérea por sus condiciones de inestabilidad hemodinámica; en 27 pacientes fue utilizado el protocolo A (Midazolam y Vecuronio o Succinilcolina) para el manejo de la vía aérea superior, en 13 pacientes se utilizó el protocolo A (Midazolam y Vecuronio o Succinilcolina) para el manejo de la vía aérea superior, en 13 pacientes se utilizo el protocolo B (Midazolam, Ketamine y Vecuronio o Succinilcolina), y en el resto de los casos se utilizo Diazepan y Meperidina. Se compara la utilización de estas drogas en el aérea de emergencia, para el manejo de la vía aérea superior en los pacientes politraumatizados.

Implicaçöes da vigilância à saúde sobre a ocorrência de fluorose dental / Considerations about sanitary vigilance on the occurence of dental fluorosis

Frente à elevada prevalência de cárie dental no Brasil, tem-se na fluoraçäo das águas de abastecimento público um método de amplo alcance, a baixo custo relativo. O uso de flúor sob diversas formas e a associaçäo de métodos, aliados à possibilidade de sua deglutiçäo por crianças, durante o período de formaçäo dos dentes, pode levar a supra-dosagens e fluoretos que resultam no desenvolvimento de fluorose dentária. Neste trabalho, verificou-se a ocorrência de fluorose dentária e a prevalência de cárie em escolares de Piratininga (SP), município que apresenta fluoretaçäo artificial das águas de abastecimento realizada por serviço autônomo. Em novembro de 1992, foi realizado um levantamento epidemiológico nas três escolas públicas do municílio. A amostra foi casual e constituída por 270 escolares, na faixa etária de 6 a 14 anos. Entre as crianças examinadas, 34,44 por cento apresentavam fluorose dentária. O elevado percentual de crianças com fluorose dentária na amostra examinada leva a reiterar a necessidade de se fazer a vigilância da fluoraçäo das águas de abastecimento público, uma vez que a ocorrência de fluorose em níveis "muito leve" a "moderado" em escolares do município surge como conseqüências de açöes deficientes no campo da vigilância à saúde