Programmed delivery of verapamil hydrochloride from tablet in a capsule device

The aim of the present work was to develop a programmed drug delivery system which would be able to release the drug after 6 h of lag time by use of hydrophilic polymers. The capsule body was made impermeable by use of formaldehyde vapor treatment, while the cap was untreated. The capsule was filled with two layered tablets (tablet-in-capsule), followed by a sodium bicarbonate:citric acid mixture (SBCM) and lactose as bulking agent. Sodium alginate, chitosan, HPMC K15 and chitosan:sodium alginate complex (CSAC) were used as the rate modulating layer. Through combined use of HPMC K15 and adjusting the ratio of CSAC, the desired lag time of 6 h was obtained. The effect of the bulking agents on the lag time were also studied and it was found that the lag time was decreased with higher amounts of lactose, and delayed dissolution and decreased lag time was observed at higher amount of effervescent mixture.O objetivo do presente trabalho foi desenvolver sistema de liberação programada de cloridrato de verapamil capaz de liberação imediata do fármaco após 6 h de intervalo de tempo usando polímeros hidrofílicos. O corpo da cápsula foi impermeabilizado por tratamento de vapor de formaldeído, enquanto a tampa não foi submetida ao tratamento. Dois comprimidos foram inseridos na cápsula (comprimidos em cápsula) seguido de mistura de bicarbonato de sódio: ácido cítrico e lactose, utilizados como excipientes. O alginato de sódio, a quitosana, o HPMC K15 e o complexo quitosana:alginato de sódio foram utilizados para modular a razão de liberação do fármaco. A combinação entre o HPMC K15 e o ajuste da proporção do complexo quitosana:alginato de sódio permitiu a liberação do fármaco após 6 h. O efeito dos excipientes na liberação do fármaco foi também avaliado. Verificou-se que o tempo de latência foi reduzido na presença de maior quantidade de lactose, enquanto o menor tempo foi observado empregando maior concentração da mistura efervescente

Impaired left ventricular filling in hypertensive left ventricular hypertrophy as a marker of the presence of an arrhythmogenic substrate.

OBJECTIVE--To assess the prevalence of ventricular late potentials and ventricular tachycardia in hypertensive subjects with left ventricular hypertrophy and to study their relation to clinical characteristics. SETTING--Teaching and general hospital in Padua. METHODS--107 hypertensive subjects with echocardiographic signs of left ventricular hypertrophy were studied with signal averaged electrocardiography and 24 hour Holter monitoring. Signal averaged electrocardiogram analysis was performed with high pass filters of 25 Hz, 40 Hz, and 80 Hz. Ventricular late potentials were considered to be present if at least two determinants of the signal averaged electrocardiogram were abnormal in one of the three filters. 70 normotensive subjects served as age matched controls. RESULTS--25% (27) of the hypertensive subjects and 6% (four) of the controls showed late potentials on signal averaged electrocardiography (P < 0.0001). The hypertensive subjects with late potentials had a higher prevalence of ventricular tachycardia (33%, 9/27) than those without late potentials (13%, 10/80; P = 0.035). Twenty nine per cent (31/107) of the hypertensive subjects had an inversion of the early to atrial filling velocity (E/A ratio < 1) on Doppler analysis of transmitral flow. Within this group the percentage of subjects with late potentials (55%, 17/31) and ventricular tachycardia (42%, 13/31) was much greater than that within the group of subjects without an inverted E/A ratio (13%, 10/76 (P < 0.0001) and 12%, 9/76 (P = 0.001) respectively). In a multivariate analysis only the E/A ratio was related to the presence or absence of either late potentials (P = 0.0001) or ventricular tachycardia (P = 0.0008). Both late potentials and ventricular tachycardia were unrelated to left ventricular mass, geometry, and systolic performance. CONCLUSIONS--A relation was found between the occurrence of ventricular tachycardia and the presence of late potentials in hypertensive subjects with left ventricular hypertrophy. Impaired left ventricular filling was the main marker for the arrhythmogenic substrate present in this disease

Sevikar (R): Combination therapy for the treatment of hypertension

Hypertension is a highly prevalent disease and one of the most important modifiable risk factors for cardiovascular disease. Hypertension remains the leading cause of mortality and the third largest cause of disability in both developed and developing countries. Although recent guidelines and advisory statements are recommending lower thresholds and goals for antihypertensive treatment, approximately two thirds of patients do not achieve the goals. In the United States only 36.8% of hypertensive patients achieve the goal o