Effectiveness of preoperative plasmapheresis in a pregnancy complicated by hyperthyroidism and anti-thyroid drug-associated angioedema.

Hyperthyroidism is not a rare entity in pregnancy and 85% of these cases attributed to Graves' disease (GD). There is no therapeutic modality for GD considered as totally safe in pregnancy. Fetal and neonatal risks of maternal hyperthyroid disease are related to the hyperthyroidism itself and/or to the medical treatment of the disease. There are no data supporting an association between congenital anomalies in the fetus and propylthiouracil (PTU). Hepatotoxicity, cytopenias--especially agranulocytosis and quite rarely, angioedema, may be seen as side effects of PTU. In this case report, we examine an instance of Graves' hyperthyroidism diagnosed during pregnancy. In this case, a serious side effect during anti-thyroid drug usage was encountered, eventually resulting in surgery in the second trimester. This intervention was assisted by the use of plasmapheresis to obtain rapid normalization of serum thyroid hormone levels.

DEET-loaded solid lipid particles for skin delivery: in vitro release and skin permeation characteristics in different vehicles.

DEET (N,N-diethyl m-toluamide) is a lipophilic compound which has a common use as an insect repellent and causes not only skin irritation but also systemic side effects at high concentrations in long-term skin application. In this study, DEET is incorporated into solid lipid particles, a colloidal drug delivery system, in order to reduce the percutaneous permeation and avoid toxic effects and also maintain drug effectiveness on the skin surface for a long duration of insect repellence. Solid lipid particles were prepared based on emulsion systems at different concentrations and after the characterization studies, the formulation with 20% lipid phase and 1:1 drug:lipid ratio was carried to in vitro release and skin permeation studies. Solid lipid particles with DEET were compared to free DEET using cream and hydrophilic gel vehicles. Results showed that incorporation of DEET into solid lipid particles reduced the release rate and skin permeation of DEET. Imaging studies using scanning electron microscopy showed that there were still solid lipid particles on skin surface after 2 h indicating that DEET could be present for a longer time on the application site.

Solid lipid nanoparticles (SLN) for topical drug delivery: incorporation of the lipophilic drugs N,N-diethyl-m-toluamide and vitamin K.

Solid lipid nanoparticles (SLN) for topical delivery were prepared by high pressure homogenization using solid lipids. The lipophilic agents DEET (N,N-diethyl-m-toluamide) and vitamin K were used as model drugs. These topical agents were incorporated into SLN which were characterized. Differential scanning calorimetry studies were performed in order to detect probable interactions in the SLN dispersions. Physical stability of SLN in aqueous dispersions and the effect of drug incorporation into SLN were investigated by photon correlation spectroscopy and zeta potential measurements. Characterization and short-term stability studies showedthat DEET and vitamin K are good candidates for topical SLN formulations.

Skin permeation of two different benzophenone derivatives from various vehicles.

The aim of this study was to determine the effects of the vehicles on the release and permeation of the UV filters. Therefore, the release and permeation of lipophilic oxybenzone and hydrophilic sulisobenzone were investigated from four different vehicles; petrolatum, o/w and w/o emulsions and hydroxyethyl cellulose (HEC) gel. Both release and permeation studies were performed by using glass diffusion cells. The vehicle in which oxybenzone has the highest released amount was petrolatum, whereas the highest released amount for sulisobenzone was obtained in HEC gel. The difference between the released amounts of oxybenzone in the other three vehicles was not significant but the released amount of sulisobenzone was least in petrolatum, whereas no significant difference was seen between o/w and w/o emulsions. The results of skin permeation experiments were similar those from release experiments. The order of permeated amounts from highest to lowest was petrolatum, o/w emulsion and HEC gel for oxybenzone, and HEC gel, o/w emulsion and petrolatum for sulisobenzone. These results demonstrate that permeation of the UV filters can be optimized by a suitable vehicle. As the percutaneous absorption of sunscreens should be avoided, the vehicle suggested for oxybenzone and sulisobenzone is o/w emulsion because of its permeation properties and cosmetic acceptance.

Percutaneous absorption of ketoprofen. I. In vitro release and percutaneous absorption of ketoprofen from different ointment bases.

Ketoprofen (KP) is a potent non-steroidal anti-inflammatory drug which is used for the treatment of rheumatoid arthritis. The oral administration of KP can cause gastric irritation and renal adverse effects. Topical application of the drug can bypass gastrointestinal disturbances and provide relatively consistent drug levels at the site of action. Since the efficacy of an ointment depends on the type of ointment base and the concentration of the drug, four different bases (white petrolatum, cold cream, hydrophilic ointment and Carbopol 940 gel) were used at 1, 3, 5, 7 and 10% concentrations of KP to evaluate the effect of ointment base and concentration. The general rank order of the drug release was found to be: Carbopol gel > hydrophilic ointment > cold cream > white petrolatum. There was a positive correlation between the concentration of KP and release rate for all bases except Carbopol gel. The in vivo percutaneous absorption of KP from different ointment bases at 3% concentration was studied by carrageenan-induced paw edema in mice. The rank order of the percent edema inhibition was as follows: Carbopol gel > or = hydrophilic ointment > cold cream > white petrolatum. There was a good correlation between the in vitro and in vivo results.

Comparative bioavailability of three batches of four commercial acetaminophen tablets.

The aim of this investigation is to evaluate four brands of acetaminophen tablets and three batches of each brand for their in vitro properties and in vivo bioavailabilities using urinary excretion data. All batches dissolved at least 80% of their acetaminophen content within 30 minutes. The differences between the dissolution rates of the batches were not found statistically significant except the batches of brand C. With respect to their dissolution rates, the brands have the following order: A less than B less than C less than D. Statistical analysis of the percent bioavailabilities and the elimination rate constants showed that there was no significant difference between brands and or between the batches. The percent excreted in the first three hours was found to be significantly different between the solution and tablet A, between tablet A and tablet C, and between Tablet A and Tablet D.

Comparative bioavailability of three commercial acetaminophen tablets.

Three brands of acetaminophen tablets marketed in Turkey were evaluated for their in vitro properties, and their in vivo bioavailabilities were determined in comparison to a standard acetaminophen solution containing an equivalent amount of the drug. The total amount of acetaminophen in urine or in tablets was determined by the colorimetric method of Welch and Conney [1965]. No significant difference between the manufacturing parameters, namely the assay, hardness, diameter and thickness of the brands was observed except that the coefficients of variation for brand A were greater than the other two brands. Brand A also disintegrated more slowly and its dissolution time (80% of the drug dissolved in 45 min) did not meet the requirements of USP XX. In vivo bioavailability studies were carried out in six healthy volunteers who received the tablets or the standard solution in a single dose, cross-over study. The urine was collected for 24 h and the total acetaminophen excreted was determined according to the method of Welch and Conney. The relative bioavailabilities for Brands A, B and C were found to be 97.87, 95.41 and 98.78%, respectively, with respect to the solution. The differences were not statistically significant and it can be concluded that all tablets were rapidly and almost completely absorbed. This study also demonstrates that there is not always a good correlation between the in vitro disintegration and dissolution tests and the in vivo bioavailability of a drug.