Selective quantitation of co-formulated ternary mixture in the presence of potential impurities by liquid chromatographic methods.

Two high performance chromatographic methods were developed and validated for the simultaneous determination of Ambroxol, Guaifenesin and Theophylline in pharmaceutical dosage forms and in the presence of Guaiacol and Caffeine as the officially stated impurities. These were a reversed phase liquid and a thin layer chromatographic methods. The liquid chromatographic separation was achieved using Inertsil ODS-3 C18 column (4.6 mm × 250 mm, 5 µm). Gradient elution was performed using a mixture of solvent A (0.05 M ammonium acetate, pH 3, adjusted with glacial acetic acid) and solvent B (methanol), at a flow rate of 1.0 mL/min. The separated peaks were detected at 260.0 nm. The thin layer chromatography was performed using HPTLC 60 F254 silica gel plates, mobile phase was consisting of ethyl acetate: methanol: acetic acid (10:0.5:1, v/v/v) and detection was performed at 254.0 nm. Validation of the developed methods was achieved according to International Conference on Harmonization (ICH) guidelines. The proposed methods were fast, accurate, precise, and sensitive. Hence, they could be employed for routine quality control of the ternary mixture in capsule and syrup dosage forms.

Development and validation of a generic RP-HPLC PDA method for the simultaneous separation and quantification of active ingredients in cold and cough medicines.

A novel generic reverse phase high performance liquid chromatography (RP-HPLC) method is developed and validated for simultaneous determination of seven pharmaceutically active ingredients, namely, acetaminophen, dextromethorphan, doxylamine, phenylephrine, guaifenesin, caffeine and aspirin. All seven ingredients were quantified in soft gel, syrup and tablet formulations of the over-the-counter US-marketed products, as per the guidelines of the International Conference on Harmonization. The separation was achieved in a 16 min run time on an Agilent Zorbax Phenyl column using a gradient method with two mobile phases. Mobile phase A was 0.15% trifluoro acetic acid in purified water and while mobile phase B was a mixture of acetonitrile and methanol (750:250 v/v) with 0.02% trifluoro acetic acid. The flow rate was 1.0 mL min-1 and injection volume was 10 µL. Detection was performed at 280 nm using a photodiode array detector. As part of the method validation, specificity, linearity, precision and recovery parameters were verified. The concentration and area relationships were linear (R2 > 0.999), over the concentration ranges 20-120 µg mL-1 for acetaminophen, 75-450 µg mL-1 for dextromethorphan, 31.25-187.5 µg mL-1 for doxylamine, 25-150 µg mL-1 for phenylephrine, 25-150 µg mL-1 for aspirin, 6.5-39 µg mL-1 for caffeine and 12-72 µg mL-1 for guaifenesin. The relative standard deviations for precision and intermediate precision were <1.5%. The proposed RP-HPLC generic method is applicable for routine analysis of cold and cough over-the-counter products.

Comparación de costes y resultados clínicos entre la administración hospitalaria o ambulatoria de omalizumab, en pacientes con asma grave no controlada / Comparison of Costs and Clinical Outcomes Between Hospital and Outpatient Administration of Omalizumab in Patients With Severe Uncontrolled Asthma

Objetivos: Evaluar los resultados clínicos y los costes de 2 estrategias de administración de omalizumab. Método: Se compararon, de forma retrospectiva, 2 cohortes de pacientes con asma grave no controlada: una, procedente del hospital A, en la que el tratamiento se administró en un centro de salud, y otra, procedente del Hospital B, con administración hospitalaria convencional. Resultados: Se estudió a 130 pacientes, 86 en A y 44 en B, 30 hombres (24%) y 100 mujeres (76%), edad 50 ± 15 años, FEV1% 67 ± 22%, índice de masa corporal (IMC) 28 ± 6 kg/m2, IgE 639 ± 747 UI/mL, seguimiento de 24 ± 11 meses (12-45), Asthma Control Test (ACT) 12 ± 4 y Asthma Control Questionnaire (ACQ) 3 ± 2, sin diferencias significativas basales entre ambas cohortes en ingresos hospitalarios ni visitas a urgencias en el año previo, ni en número de pacientes con esteroides orales. Al comparar la situación basal y tras los 12 meses de tratamiento, se observaron diferencias significativas en ACT (p < 0,001), ACQ (p < 0,001) y mejoría en el FEV1% (p < 0,001), reducción en número de ingresos (p < 0,001), días de hospitalización (p < 0,001), visitas a urgencias (p < 0,001), ciclos y dosis de esteroides p < 0,001) respecto al año previo, tanto individualmente como en conjunto. Los costes de hospitalización, visitas a urgencias, visitas no programadas a Primaria y al neumólogo se redujeron significativamente en ambos hospitales, pero los costes de administración y desplazamiento fueron un 35% inferiores con la pauta ambulatoria en A. Conclusión: La administración ambulatoria de omalizumab en los centros de salud consigue los mismos resultados clínicos que una pauta de administración hospitalaria, con menores costes

Objectives: To compare clinical outcomes and costs between two administration strategies of omalizumab treatment. Method: We evaluated two cohorts of patients with uncontrolled severe asthma over a 1-year period. Patients received the treatment in the primary care center in Hospital A and conventional hospital administration in Hospital B. Results: We studied 130 patients, 86 in Hospital A and 44 in Hospital B, 30 men (24%) and 100 women (76%), age 50 ± 15 years, FEV1% 67 ± 22%, body mass index (BMI) 28±6kg/m2, 639 ± 747 UI IgE/mL, followed for 24 ± 11 months (12-45), Asthma Control Test (ACT) score 12 ± 4 and Asthma Control Questionnaire (ACQ) 3±2. There were no significant pretreatment differences between the groups in hospital admissions and emergency room visits in the previous year, nor in proportion of patients receiving oral steroids. Evaluations were performed at baseline and after 12 months of treatment, revealing significant differences in ACT (P < 0.001), ACQ (P<0.001), improvement in FEV1% (P < 0.001), reduction in total admissions (P < 0.001), days of hospitalization (P<0.001), emergency room visits (P<0.001), cycles and doses of oral steroids (P < 0.001) compared to the previous year. Hospitalization costs, emergency room visits, unscheduled visits to primary care and to the pulmonologist were significantly reduced in each hospital and on the whole, but administration and travel costs were 35% lower in the ambulatory strategy adopted in Hospital A

Methods for reduction of cohesive forces between carrier and drug in DPI formulation.

Dry powder inhaler (DPI) has become a well accepted drug delivery for pulmonary system to treat many related diseases including symptomatic and life threatening diseases. Successful delivery of dry powder to the lung requires careful consideration of powder production process, formulation and inhaler device. The formulation of DPI mostly comprises of lactose as a carrier for drug delivery. In DPI formulation, particulate interactions within the formulation govern both the drug dissociation from carrier particles and the disaggregation of drug into primary particles with a capacity to penetrate deep into lung. Two contradictory requirements must be fulfilled for this type of dry powder formulation. On one hand, adhesion between carrier and drug must be sufficient for the blend drug/carrier to be stable. On the other hand, adhesion drug/carrier has to be weak enough to enable the release of drug from carrier during patient inhalation. Thus the carrier use restricted due to detachment problem. Different methods are proposed to reduce the cohesive forces between drug and carrier to desired level. Various studies conducted for understanding the mechanism of deposition into lungs and making formulation with optimum carrier drug cohesive force. This review provides information on various processes involved in reducing the cohesive forces between drug and carrier, to a required level.

Product lifecycle approach to cascade impaction measurements.

Over the lifecycle of an orally inhaled product (OIP), multi-stage cascade impactor (CI) measurements are used for different purposes and to address different questions. Full-resolution CIs can provide important information during product development and are widely used but are time- and resource-intensive, highly variable, and suboptimal for OIP quality control (QC) testing. By contrast, Efficient Data Analysis (EDA) combined with Abbreviated Impactor Measurement (AIM) systems pertinent either for QC and-possibly-for adult Human Respiratory Tract (pHRT) has been introduced for OIP performance assessment during and post-development. This article summarizes available evidence and discusses a strategy for using either abbreviated or full-resolution CI systems depending on the purpose of the measurement, such that adequate, accurate, and efficient testing of aerodynamic particle size distribution (APSD) of OIPs can be achieved throughout the lifecycle of a product. Under these proposals, a comprehensive testing program should initially be conducted by full-resolution CI in OIP development to ascertain the product's APSD. Subsequently, correlations should be established from the selected AIM CIs to the corresponding full-resolution system, ideally developing specifications common to both techniques. In the commercial phase, it should be possible to release product using AIM/EDA, keeping the full-resolution CI for investigations, change control, and trouble-shooting, thus optimizing resources for APSD characterization throughout the product lifecycle. If an in vitro-in vivo relationship is established and clinically relevant sizes are known, an AIM-pHRT could serve as a quick indicator that clinically relevant fractions have not changed and also, in the management of post-approval changes.

[Determination of multicomponent contents in anticold solution by high performance liquid chromatography].

A high performance liquid chromatographic method has been successfully used to separate and determine the six drugs in an anticold solution. In the anticold solution, potassium guaiacol sulfonate, acetaminophen, D,L-methylephedrine, and caffeine were analyzed with a column of Zorbax ODS, by using the mobile phase of MeOH-0.05 mol/L KH2PO4-H3PO4 (250 : 750 : 0.5) and UV detector at 214 nm, dextromethorphan HBr and chlorpheniramine maleate were analyzed with the same column, by usingthe mobile phase of MeOH-H2O-HsPO4-SLS (80 : 20 : 0.5 : 0.2) and UV detector at 260 nm. This method is proved to be very effective to separate the six drugs mentioned above. For potassium guaiacol sulfonate, acetaminophen, D,L-methylephedrine, caffeine, dextromethorphan HBr and chlorpheniramine, the response values were linear between 1.0-10 microg, 5.0-50 microg, 0.25-2.5 microg, 0.5-5 microg, 0.25-2.5 microg, 0.05-0.5 microg respectively and the recoveries were 100.53% +/- 1.12%, 100.19% +/- 0.58%, 99.4% +/- 1.60%, 99.55% +/- 1.01%, 99.37% +/- 1.52%, 99.01% +/- 1.20% (n=5) respectively.