Treatment of the Budd-Chiari syndrome with percutaneous transluminal angioplasty. Case report and review of the literature

A patient with the Budd-Chiari syndrome due to membranous obstruction of the right hepatic vein and long segmental obstruction of the inferior vena cava who was successfully treated with percutaneous transluminal angioplasty is described. Review of the literature revealed 14 prior cases of balloon dilatation of the hepatic venous system: 10 of the hepatic portion of the inferior vena cava, three of the right hepatic vein, and one of the left hepatic vein. Follow-up ranged from six months to 37 months. No serious complications were reported. All attempts at dilatation were successful, but reocclusion occurred in six patients, three of whom had occlusion of the hepatic vein. All but one patient with reocclusion, however, underwent repeated angioplasty, which was successful in all cases attempted. Two patients who had repeated angioplasty required no further therapy, but two patients required a total of three angioplasties and two patients required four angioplasties. Successful angioplasty was accompanied by resolution of clinical symptoms in all patients described. It is concluded that percutaneous transluminal angioplasty is a safe and effective mode of therapy in the management of the Budd-Chiari syndrome due to membranous obstruction of the hepatic portion of the inferior vena cava or the hepatic veins.     

Investigating the effect of dehydration conditions on the compactability of glucose

Hydrates are commonly found in pharmaceutical ingredients either in excipients or in the active pharmaceutical ingredient form. There is always the possibility that the processing involved in manufacturing can result in the dehydration of the hydrate components. It has been seen that different dehydration conditions can have an effect on the behavior of the final product; however this area has not been fully investigated. In this work, glucose monohydrate powder was dehydrated at four different conditions and then compressed to see the effect on the hardness of the compacts. Various analytical tools such as inverse gas chromatography, differential scanning calorimetry, X-ray powder diffractometry and scanning electron microscopy were used to determine any differences in the properties of the dehydrates and correlated with the obtained compact hardness. Annealing studies were performed to determine the effect of storage on the dehydrated materials both before and after compression. It was observed that while annealing of the powders did have an impact, annealing of the compacts did not influence the hardness. The results of the characterization and annealing studies showed that the difference in the behavior of glucose dehydrates were due to the presence of amorphous regions within the particulates.     

Evaluation of the Crystallization Tendency of Commercially Available Amorphous Tacrolimus Formulations Exposed to Different Stress Conditions

Purpose

Tacrolimus, an immunosuppressant, is a poorly water soluble compound whereby the commercially available capsule formulations contain the drug in amorphous form. The goal of this study was to evaluate the robustness of the innovator product and five generic formulations to crystallization following storage at stress conditions.

Methods

Products were purchased from a pharmacy and stored at 40°C/75% relative humidity (RH), open dish conditions. Crystallinity was determined using X-ray diffraction. The quantity of the ingredients in the formulations were determined using different approaches and the various factors that might cause instability in the formulations were studied.

Results

After 4 weeks of open dish storage at 40°C/75% RH, one of the generic formulations showed evidence of tacrolimus crystallization. Further investigations revealed batch-to-batch variations in crystallization tendency with the extent of crystallinity varying between 50 and 100% for different batches. Crystallization was also observed at lower storage temperatures (30°C) when the RH was maintained at 75%. It was found that crystallization could be induced in a model formulation by wet granulating an ethanolic solution of the drug with lactose and drying at 60–70°C followed by exposure to stress conditions.

Conclusions

It seems probable that the generic that was susceptible to crystallization contains amorphous drug physically mixed with polymeric excipients, rather than as an amorphous solid dispersion. This study highlights the importance of considering the manufacturing process on the stability of the resultant amorphous product.

     

Investigation of the Milling-Induced Thermal Behavior of Crystalline and Amorphous Griseofulvin

Purpose  

To gain a better understanding of the physical state and the unusual thermal behavior of milled griseofulvin.     

Non-Sink Dissolution Behavior and Solubility Limit of Commercial Tacrolimus Amorphous Formulations

An increasing number of drugs with low aqueous solubility are being formulated and marketed as amorphous solid dispersions because the amorphous form can generate a higher solubility compared to the crystalline solid. The amorphous solubility of a drug can be determined experimentally using various techniques. Most studies in this area investigate the drug in its pure form and do not evaluate any effects from other formulation ingredients. In this study, we use 6 marketed amorphous oral drug products, capsules containing 5 mg of tacrolimus, and various excipients, consisting of 1 innovator product and 5 generics. The amorphous solubility of tacrolimus was evaluated using different techniques and was compared to the crystalline solubility of the drug. Dissolution of the different products was conducted under non-sink conditions to compare the maximum achieved concentration with the amorphous solubility. Diffusion studies were performed to elucidate the maximum flux across a membrane and to evaluate whether there was any difference in the thermodynamic activity of the drug released from the formulation and the pure drug. The amorphous solubility of tacrolimus was found to be a factor of 35 higher than the crystalline solubility. The maximum concentration obtained after dissolution of the capsule contents in non-sink conditions was found to match the experimentally determined amorphous solubility of the pure drug. Furthermore, the membrane flux of tacrolimus following dissolution of the various formulations was found to be similar and maximized. This study demonstrates a link between key physicochemical properties (amorphous solubility) and in vitro formulation performance.     

The Open Ring A New Imaging Sign in Demyelinating Disease

Because demyelinating disease of the brain occasionally presents with large ring-enhancing lesions on computed tomography (CT) scans and magnetic resonance images (MRis), the authors sought to determine whether the ring pattern differed from that found in other common brain lesions with ring enhancement. Published MRI and CT scans of patients with adrenoleukodystrophy (23), and multiple sclerosis or similar demyelinating disorders (21), as well as a variety of tumors (44) and infections (44) matched to the demyelinating lesions by year of publication, in which ring enhancement was evident, were photographed. Photographs without diagnostic identification were presented randomly to two independent observers. The observers rated the contrast enhancement pattern as (1) open ring, with enhancement in the border of the lesion abutting the white matter; (2) closed ring; or (3) uncertain. For all diagnostically certain cases (n = 112), interrater agreement was excellent (κ = 0.75). As an average of the two reviewers, scans for 11 of 132 cases were read as uncertain; 89% of adrenoleukodystrophy cases, 41% of the multiple sclerosis cases, 3% of tumors, and 9% of infections were classified as having the open-ring pattern. Overall, 66% of demyelinating lesions had an open-ring pattern compared with 7% of the nondemyelinating lesions (χ² = 41.2, p < 0.0001 ). An open-ring pattern of enhancement is more likely to be associated with demyelinating lesions than with nondemyelinating lesions .     

von Willebrand disease: a laboratory approach

von Willebrand disease (VWD) is a common inherited bleeding disorder. Accurate diagnosis and classification of VWD is crucial for clinical management. A detailed clinical history, including that of bleeding, is required. A family and drug history are also important. Genetic factors such as blood group, and environmental factors such as stress, trauma, pregnancy and inflammation should also be considered. The age, ethnic group and hormonal status could also affect the von Willebrand factor (VWF) levels. No single test is robust enough to detect all variants of VWD. In view of the heterogeneity of the disease and limitations in assays, a battery of tests should be performed before a final diagnosis can be reached. These include the screening coagulation tests, factor VIII:C assay, VWF antigen assay, assessment of functional VWF which includes VWF ristocetin cofactor assays, VWF collagen binding assay, ristocetin-induced platelet aggregation and VWF multimer analysis. The newer ELISA techniques based on VWF binding with factor VIII glycoprotein (Gp) 1b and cerebrosides have also helped in determining certain unusual forms of VWD. The advent of new systems such as platelet function analysers (PFA), thromboelastography (TEG) and clot signature analysers (CSA), which are designed to assess either the primary platelet function or as a global haemostasis screen, have facilitated and simplified the diagnosis. However, few centres all over the world can perform all these expensive tests to provide a final diagnosis of VWD. We reviewed the laboratory investigations required for a diagnosis of VWD. Apart from congenital VWD, the possibility of acquired VWD should be considered in those with a negative past history of bleeding or in the presence of an underlying disease.