ABSTRACT
A 26-year-old Malaysian woman (childbearing age) attended a private primary care clinic with a known case of gastroesophageal reflux disease (GERD) and complained of persistent nausea and a few episodes of vomiting. She had no known drug allergy, no surgical history, no hospitalization in the last two years, was a non-smoker, and no history of drug or alcohol abuse. The patient was prescribed Tab metoclopramide 10 mg TDS and Tab ranitidine 150 mg BD for five days. About 30 min after oral administration of both medicines, her eyes rolled involuntary upward, leading to lateral deviation of the eyes, and mouth jaws clenched as if “dislocated jaws.” The patient was immediately brought into an emergency department (ED) of a public tertiary care hospital. A drug challenge test was done which resulted in the withdrawal of metoclopramide. The accompanied sister later disclosed that the patient had taken metoclopramide and ranitidine from a private clinic earlier in the day. The patient self-assumed to have a sudden seizure, due to excessive hot weather and dehydration. A slow intravenous infusion of 50 mg/mL diphenhydramine hydrochloride in 0.9% w/v NaCl 100 mL was administered stat. Consequently, the symptoms vanished after approximately 30 min of the therapy, devoid of relapse. The patient was discharged from ED post 8 hours of monitoring with complete recovery. Physicians frequently prescribe metoclopramide to treat nausea and vomiting, which may cause adverse drug reaction of acute dystonic oculogyric crisis (OGC). Due to its unwanted and unpredictable extrapyramidal symptoms, metoclopramide should be prescribed and dispensed with caution. Thorough history taking at ED is imperative for correct early diagnosis and treatment, as metoclopramide-induced dystonic OGC has a high probability of confusion with other causes of dystonia such as conversion and seizures, encephalitis, tetanus, and hypercalcemic tetany.
ABSTRACT
A rapid and sensitive stability indicating RP-HPLC method is developed for the simultaneous estimation of Methylparaben, Mometasone Furoate and Eberconazole Nitrate in topical formulations. Chromatographic separation was achieved on Waters Xterra C18 (150 × 4.6 mm, 5μm) using a mobile phase constituted of water and methanol (35:65, v/v) at a flow rate of 1.50 mL/min and column temperature of 30˚C. All three components were measured with uv detection at 235 nm. Force degradation study was conducted to determine Methylparaben, Mometasone Furoate and Eberconazole Nitrate in the presence of degradants and excipients peaks. Developed method was validated for method precision, specificity, linearity, accuracy, robustness and solution stability as per ICH guidelines. Method is showing linearity in the range of 0.25-188, 0.50-75 and 2.0- 750 μg/mL for Methylparaben, Mometasone Furoate and Eberconazole Nitrate respectively. The method was proved to be robust by conducting DOE study. The method is suitable for stability studies, routine analysis and quality control of topical formulations containing these components, either alone or in combination.
ABSTRACT
The characteristics of a new Polyvinylacetate/Povidone based excipient, Kollidon® SR were evaluated for application in extended release matrix tablets. The effects of the following formulation and process variables on tablet properties and drug release were tested: Kollidon® SR concentration in the tablet, addition of external binder for wet granulation, presence of an enteric polymer in the matrix, method of manufacturing and compression force. The similarities in release profiles were evaluated by applying the model independent f2 similarity factor. It was found that Kollidon® SR is suitable for pH-independent extended release matrix tablets. A minimum concentration of 30% polymer was necessary to achieve a coherent matrix, able to extend the release of the incorporated drugs. Increasing the Kollidon® SR concentration in the tablet led to a slower drug release. Drug release followed square root of time dependent kinetics, thus indicating a diffusion-controlled release mechanism. The drug release was influenced by the aqueous solubility of the drug. The drug release rate was faster for wet granulation than direct compression, thus making direct compression the method of choice for manufacturing Kollidon® SR extended release systems. It was found that Kollidon® SR was the main release controlling agent in the presence of an external binder or enteric polymer in the matrix. A significant reduction in the dissolution rates associated with an increase in tablet hardness was observed during the stability test under accelerated conditions. The developed propranolol matrix tablets formulation was compared to the reference listed product (Inderal® LA capsules). It was concluded that Kollidon® SR is a potentially useful excipient for the production of pH-independent extended release matrix tablets.