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The objective of the present study was to formulate a hydroxypropyl methylcellulose (HPMC) gel drug reservoir system with ethanol-water as a solvent system and limonene as a penetration enhancer for enhancing the transdermal delivery of nicorandil so as to develop and fabricate a membrane-moderated transdermal therapeutic system (TTS). The in vitro permeation of nicorandil was determined across rat abdominal skin from a solvent system consisting of ethanol or various proportions of ethanol and water. The ethanol-water (70:30 v/v) solvent system that provided an optimal transdermal permeation was used in formulating an HPMC gel drug reservoir system with selected concentrations (0% w/w, 4% w/w, 6% w/w, 8% w/w or 10% w/w) of limonene as a penetration enhancer for further enhancement of transdermal permeation of nicorandil. The amount of nicorandil permeated in 24 h was found increased with an increase in the concentration of limonene in the drug reservoir system up to a concentration of 6% w/w, but beyond this concentration there was no further increase in the amount of drug permeated. The flux of nicorandil was 370.9 ± 4.2 µg/cm²·h from the drug reservoir system with 6% w/w of limonene, which is about 2.6 times the required flux to be obtained across rat abdominal skin for producing the desired plasma concentration for the predetermined period in humans. The results of a Fourier Transform Infrared study indicated that limonene enhanced the percutaneous permeation of nicorandil by partially extracting the stratum corneum lipids. It is concluded that the HPMC gel drug reservoir system prepared with a 70:30 v/v ethanol-water solvent system containing 6% w/w of limonene is useful in designing and fabricating a membrane-moderated TTS of nicorandil.

[1] Height and gravity measurements observed along a profile across the epicentral area before and after the January 26, 2001, M w 7.6 Bhuj earthquake show a maximum uplift of 1.57 ± 0.5 m and a corresponding gravity change of À393 ± 18 mGal. A best-fit, singledislocation model inverted from the height-changes using non-linear optimization methods indicates that the high-slip rupture was well contained in the aftershock zone and likely did not break to depths shallower than $10 km. Source parameters arrived in the present study agree well with those provided by seismic inversions and the distribution of aftershocks. Gravity data over the epicentral area are well modeled by the preferred model; however, a strong influence of shallow hydrological processes is inferred for three sites, two located on the Banni plains, whose mean gravity change $280 mGal suggests a total mass redistribution of as much as 2.9 Mt.

We studied paternal exposure to Agent Orange and its dioxin contaminant (2,3,7,8-tetrachlorodibenzo-p-dioxin) and preterm birth, intrauterine growth retardation, or infant death in veterans of Operation Ranch Hand, the unit responsible for spraying herbicides during the Vietnam war. A Comparison group of Air Force veterans who served in Southeast Asia during the same time period and who were not occupationally exposed to herbicides was included. We studied children conceived during or after the father's service in Southeast Asia and based exposure on paternal dioxin measured in 1987 or 1992 extrapolated to the time of conception of the child. We assigned each child to one of four exposure categories: Comparison and three Ranch Hand categories (Background, Low, High). Children in the High (relative risk = 1.3) and Background (relative risk = 1.4) categories were at increased risk of preterm birth. The risk of intrauterine growth retardation was not increased in any exposure category. The risk of infant death was increased in all Ranch Hand children, with the greatest increases in the High (relative risk = 4.5) and Background (relative risk = 3.2) categories. These patterns indicate that the increases in the relative risk of preterm birth and infant death may not be related to paternal dioxin level.