Data regarding particle size distribution, thermal properties and gaseous phase hydration of co-milled solid dispersions composed of tadalafil and Soluplus

A mechanical activation of the solid particles upon high-energy ball milling may considerably change the physicochemical properties of pharmaceutical compounds, including the morphology, particle size distribution, thermal properties, and surface interactions with water vapour upon gaseous phase hydration. Assessment of these changes is crucial for optimizing the manufacturing process of enabling drug products. In this article, we provide a detailed characterization of binary co-milled solid dispersions composed of tadalafil and Soluplus using a laser diffraction method, differential scanning calorimetry (DSC), gravimetric measurements and solid state (1)H- NMR spectroscopy. The data presented in this article is directly related to our previously published research article. They complement information on the impact that both formulation and process variables may have on the properties of these binary powder formulations

Pheochromocytoma in 8-year observation at a single endocrinological center in Wroclaw

Wstęp: Guz chromochłonny występuje rzadko, powoduje zwykle nadciśnienie tętnicze i różnorodne, zmienne objawy kliniczne, co często utrudnia wczesne rozpoznanie i leczenie. Celem niniejszej pracy było przedstawienie danych klinicznych, efektywności diagnostyki i leczenia chorych z pheochromocytoma w ośrodku wrocławskim w okresie 8 lat. Materiał i metody: Wśród 37 chorych z pheochromocytoma leczonych w latach 2000-2007 w Klinice Endokrynologii, Diabetologii i Leczenia Izotopami Akademii Medycznej we Wrocławiu były 23 kobiety (23-75 lat) oraz 14 mężczyzn (17-74 lat). Zbadano częstość występowania poszczególnych objawów klinicznych, przydatność zastosowanych metod diagnostycznych i efekty leczenia. Wyniki: Czas trwania choroby do momentu rozpoznania wynosił od 2 miesięcy do 16 lat. Najczęstsze objawy to: nadciśnienie tętnicze napadowe lub stałe, tachykardia, bóle głowy, wzmożona potliwość, niepokój. Najczulszą laboratoryjną metodą diagnostyczną był pomiar stężenia metoksypochodnych katecholamin w moczu dobowym. Tomografia komputerowa u wszystkich chorych wykazała obecność guza nadnercza, częściej prawego; w 1 przypadku guz był umiejscowiony w ścianie pęcherza moczowego. Po operacji nadciśnienie tętnicze ustąpiło u 59% pacjentów, obniżyło się u 26,8%, a u 13,9% nie obserwowano poprawy. U 2 chorych guz był złośliwy, 1 kobieta zmarła po zabiegu. U 8 stwierdzono zespół MEN 2A. Wnioski: Rozpoznania pheochromocytoma zwykle dokonuje się po długim czasie trwania choroby. Najbardziej typowym objawem jest nadciśnienie tętnicze napadowe, które występuje jedynie u około 40%, inne objawy są niespecyficzne. Najbardziej przydatne diagnostycznie jest stwierdzenie podwyższonego wydalania metoksykatecholamin w moczu dobowym. Z badań obrazowych najbardziej efektywna jest tomografia komputerowa. Chorzy z pheochromocytoma powinni być rutynowo diagnozowani w kierunku współistnienia innych endokrynopatii, a szczególnie raka rdzeniastego i pierwotnej nadczynności przytarczyc - składowych zespołu MEN 2A.Introduction: Pheochromocytoma is rare tumor with a highly variable clinical presentation. This report provides clinical picture, efficiency of diagnostics and treatment of pheochromocytoma in 8-years in the endocrinological center in Wroclaw. Material and methods: The records of 37 patients with pheochromocytoma were identified, who were treated in 2000-2007 in the Department of Endocrinology, Diabetology and Isotope Treatment in Wroclaw. There were 23 women (age 23-75 year) and 14 men (age 17-74). We studied frequency of clinical signs, usefulness of diagnostic methods and efficacy of treatment. Results: The duration of the clinical history ranged from 2 months to 16 years. The most frequent symptoms were: hypertension paroxysmal and constant, palpitations, headache, sweating and anxiety. The most sensitive diagnostic method was increased concentration of urinary metanephrine in 24-hour urine. Computed tomography was the most widely used method for tumor localization. Adrenal pheochromocytoma was detecting by CT in all patients, predominated in right adrenal, in 1 case in urinary bladder. Surgery caused remission of hypertension in 59%, improvement in 26.8%, and no changes in 13.9% of patients. Malignancy was reported in 2 cases, 1 woman died after surgery. MEN 2A occur in 21.6%. Conclusions: The diagnosis of pheochromocytma is usually made after long duration of the disease. The study confirms that clinical presentation of pheochromocytoma is variable and nonspecific, this finding makes the diagnosis very difficult. The most typical symptom is paroxysmal hypertension, which is present only in 40%, other symptoms are nonspecific. The measurement of 24-hour urinary metanephrines was the best indicator. CT was almost always successful in localizing the tumor. Patients with pheochromocytoma should be consider for other endocrine diseases especially medullary carcinoma, primary hyperparathyroidism and other component of MEN 2A

How rotational speed of planetary ball mill and polymer load influence the performance and water vapor sorption in solid dispersions composed of tadalafil and soluplus

The presence of residual water may deteriorate the performance of amorphous solid dispersions prepared by ball milling, affecting molecular mobility, crystallinity, particle size and finally, the drug dissolution rate. As the stability of these metastable systems depend on both formulation and process variables, the aim of this study was to assess for the first time, the impact that the polymer load and the rotational speed applied upon high energy ball milling could have on the performance of binary co-milled solid dispersions composed of tadalafil (a hydrophobic crystalline drug) and Soluplus (an amphiphilic, hygroscopic amorphous polymer). Each of these variables was tested at three levels. Scanning electron microscopy, laser diffraction and X-ray powder diffraction were used to analyze morphology, particle size distribution and crystallinity of ball milled formulations respectively. Dissolution studies were also carried out. Advanced tools of applied physics, namely solid state 1H NMR and relaxometry were used to assess the structure and water mobility upon gaseous phase hydration on storage. It was shown that both tested variables determined the particle size of the formulation. When the rotational speed of 400 rpm was used, all solid dispersion were XRD-amorphous, but to ensure the immediate release of tadalafil its micellar solubilization in Soluplus was necessary. While the formulation was exposed to water vapor, the hydration level increased with an increasing polymer load as well. Hence, the rotational speed governed the space available for the adsorption of water molecules and their organization in a monolayer or multilayers. Such behavior may have impact on the kinetics of the amorphous drug recrystallization, and finally deteriorate its dissolution

Ophthalmic applicator displacement as a method of treating large diffuse uveal melanomas

Purpose: The presentation of results of an ophthalmic plaque displacement as a brachytherapy treatment method of large diffuse uveal melanomas. Material and methods: This was a retrospective analysis of treatment results of 9 patients with large diffuse uveal melanomas using ophthalmic plaque displacement. Patients were treated with this method in our center between 2012 and 2021 (last follow-up visit in 2023). To achieve appropriate radiation dose distribution for large tumors with a base greater than 18 mm, brachytherapy ($^{106}$Ru in 7 patients and $^{125}$I in 2 patients) with applicator displacement was used as primary treatment. Median follow-up was 2.9 years, and for patients with positive primary treatment results, it was 1.7 months. Median time to local relapse was 2.3 years. Results: In 5 patients, a positive result of local treatment was obtained, out of whom, one patient underwent enucleation due to complications. In the next 4 cases, local recurrence developed. In all tumors, the use of applicator displacement method caused that planning target volume (PTV) was effectively covered with treatment isodose. Conclusions: Brachytherapy with ocular applicator displacement allows for the treatment of tumors with base measurements larger than 18 mm. The application of this method may be considered as an alternative for eye enucleation in particular cases of large diffuse tumors, such as a neoplasm of the eye with vison, or when a patient does not consent to enucleation

Atypical Hemolytic Uremic Syndrome (aHUS) and Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency (SCID)—Two Diseases That Exacerbate Each Other: Case Report

Hemolytic uremic syndrome (HUS) is defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Atypical HUS (aHUS), distinguished by its etiology, is caused by uncontrolled overactivation of the alternative complement pathway. The correct diagnosis of aHUS is complex and involves various gene mutations. Severe combined immunodeficiency (SCID), characterized by severe T-cell lymphocytopenia and a lack of antigen-specific T-cell and B-cell immune responses, is of seldom occurrence. In 10–15% of pediatric patients, SCID is caused by adenosine deaminase (ADA) deficiency. The authors describe the case of a boy who suffered from both aHUS and ADA-deficient SCID. At the age of 9 months, the patient presented acute kidney injury with anuria and coagulopathy. The diagnosis of aHUS was established on the basis of alternative complement pathway deregulation and disease-associated gene mutations. Further examination revealed immune system failure and, at the age of 13 months, the ADA deficiency was confirmed by genetic tests and the boy was diagnosed with ADA-SCID. ADA SCID has recently been described as a possible triggering factor of aHUS development and progression. However, more research is required in this field. Nevertheless, it is crucial in clinical practice to be aware of these two co-existing life-threatening diseases