New quantitative methods for evaluation of dynamic changes in QT interval on 24 hour Holter ECG recordings: QT interval in idiopathic ventricular fibrillation and long QT syndrome

OBJECTIVES: To introduce a nomogram of the normal QT interval at various heart rates measured from 24 hour Holter ECG recordings in healthy subjects with respect to age and sex and to use the nomogram to characterise dynamic changes in QT interval in patients with idiopathic ventricular fibrillation (IVF) and the long QT syndrome (LQT). METHODS: The study group consisted of 422 subjects: 249 healthy men ranging in age from 21–88 years (mean (SD) 47 (20) years) and 173 healthy women ranging in age from 21–85 years (47 (19) years). In addition, seven men with IVF ranging in age from 33–53 years (43 (9) years) and five women with LQT ranging in age from 20–55 years (37 (14) years) were studied. For each subject, QT interval and heart rate were determined automatically from 24 hour Holter ECG digital data—namely, QT interval was measured from signal averaged ECG waves obtained by averaging consecutive sinus beats during each 15 second period over 24 hours. Data were grouped and averaged at an interval of 5 beats/min for heart rates ranging from 46–120 beats/min. RESULTS: In healthy subjects aged < 50 years and ⩾ 50 years QT intervals were longer in women than in men. QT intervals were longer in both men and women aged ⩾ 50 years than in ages < 50 years. From these findings a nomogram of QT interval at varying heart rates adjusted for age (younger group aged < 50 years or older group aged ⩾ 50 years) and sex was determined. In patients with IVF, QT intervals were significantly shorter at slower heart rates than normal values obtained from the nomogram. In patients with LQT, QT intervals were significantly longer at both faster and slower heart rates than normal values. CONCLUSIONS: The nomogram of QT interval at varying heart rates adjusted for sex and age could be used to assess dynamic changes of QT interval of various pathological conditions. For example, patients with IVF had shorter QT interval at slower heart rates, a finding suggestive of arrhythmogenicity of this specific syndrome at night. Patients with LQT had prolonged QT interval at specific heart rate ranges depending on their genotype

Development and evaluation of Cetirizine HCl taste-masked oral disintegrating tablets

The purpose of the current study was to mask the taste of cetirizine HCl and to incorporate the granules produced in oral disintegrating tablets (ODT). The bitter, active substance was coated by fluidized bed coating using Eudragit® RL30-D at levels between 15% and 40% w/w. The ODTs were developed by varying the ratio of superdisintegrants such as sodium croscarmellose, crospovidone grades and low substituted hydroxypropyl cellulose (L-HPC). A direct compression process was used to compress the ODTs under various compaction forces to optimize tablet robustness. The properties of the compressed tablets including porosity, hardness, friability and dissolution profiles were further investigated. The in vitro and in vivo evaluation of the tablet disintegration times showed almost identical rapid disintegration below 10 s at the optimal levels of each superdisintegrant. Finally, the taste and sensory evaluation in human volunteers demonstrated excellence in masking the bitter active and tablet palatability