Impact of incorporated drugs on material properties of amorphous solid dispersions.

Formulation development of amorphous solid dispersions (ASD) still is challenging although several poorly water-soluble drugs have been marketed using this technique. During development of novel drugs, the selection of the preparation technique and polymer matrix is commonly performed for the certain drug via screening tools. However, if general trends regarding material properties are to be investigated, this approach is not beneficial, although often utilized in literature. The main component of the ASD usually is the polymer and thus it predominantly determines the material properties of the system. Therefore, to study the impact of different drugs and their drug loads on mechanical properties and wettability, three poorly soluble model drugs with drug loads ranging from 10% to 40% were incorporated into copovidone via hot-melt extrusion. The obtained extrudates were subsequently characterized regarding mechanical properties by applying diametral compression test and nanoindentation and the results were compared to the performance during tablet compression. Incorporation of all tested drugs resulted in a similar increase in brittleness of the ASDs, whereas the Young's modulus and hardness changed differently in dependence of the incorporated drug. These observations correlated well with the performance during tablet compression and it was concluded, that the brittleness seemed to be the predominant factor influencing the compression behavior of copovidone-based ASDs. Furthermore, the degree of water absorption and wettability was assessed by applying dynamic vapor sorption experiments and contact angle measurements. Here, the incorporated drugs impacted the contact angle to different degrees and a strong correlation between the contact angle and disintegration time was observable. These results highlight the importance of thorough characterization of the ASDs as it helps to predict their performance during tablet compression and thus facilitates the optimal selection of excipients.

Placental Sonolucencies in the First Trimester: Incidence and Clinical Significance.

OBJECTIVES: The aims of this study were to determine the incidence of placental sonolucencies on first-trimester screening sonograms in a general obstetric population and assess whether these findings are associated with adverse obstetric outcomes. METHODS: A retrospective cohort analysis of 201 pregnant patients screened at a high-risk prenatal diagnostic center was conducted with first-trimester cine clips reviewed by 2 radiologists. Placental sonolucencies were defined as intraplacental anechoic or heterogeneous areas 0.7 cm or greater. Obstetric and neonatal outcomes were collected by chart review. RESULTS: Placental sonolucencies 0.7 cm or greater were seen in 45 (22.4%) of first-trimester ultrasound examinations. The ultrasonographic presence of a placenta previa, marginal sinus, and subchorionic hemorrhage was not more common in those with placental sonolucencies 0.7 cm or greater (P > 0.05). Sonolucencies were not associated with prior cesarean deliveries (P > 0.05). Both the groups with and without sonolucencies 0.7 cm or greater had similar rates of antepartum hemorrhage, preeclampsia, preterm delivery, cesarean delivery, postpartum hemorrhage, and delivery of small-for-gestational-age infants. One placenta accreta and no fetal demises occurred in the study population. CONCLUSIONS: Placental sonolucencies detected on first-trimester screening sonograms in the general obstetric population are not predictive of poor obstetric outcomes.

Parenchymal Volumetric Assessment as a Predictive Tool to Determine Renal Function Benefit of Nephron-Sparing Surgery Compared with Radical Nephrectomy.

PURPOSE: To develop a preoperative prediction model using a computer-assisted volumetric assessment of potential spared parenchyma to estimate the probability of chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m(2)) 6 months from extirpative renal surgery (nephron-sparing surgery [NSS] or radical nephrectomy [RN]). PATIENTS AND METHODS: Retrospective analysis of patients who underwent NSS or RN at our institution from January 2000 to June 2013 with a compatible CT scan 6-month renal function follow-up was performed. Primary outcome was defined as the accuracy of 6-month postoperative eGFR compared with actual postoperative eGFR based on root mean square error (RMSE). Models were constructed using renal volumes and externally validated. A clinical tool was developed on the best model after a given surgical procedure using area under the curve (AUC). RESULTS: We identified 130 (51 radical, 79 partial) patients with a median age of 58 years (interquartile range [IQR] 48-67) and preoperative eGFR of 82.1 (IQR 65.9-104.3); postoperative CKD (eGFR <60) developed in 42% (55/130). We performed various linear regression models to predict postoperative eGFR. The Quadratic model was the highest performing model, which relied only on preoperative GFR and the volumetric data for a RMSE of 15.3 on external validation corresponding to a clinical tool with an AUC of 0.89. CONCLUSION: Volumetric-based assessment provides information to predict postoperative eGFR. A tool based on this equation may assist surgical counseling regarding renal functional outcomes before renal tumor surgical procedures.

Imaging manifestations of malignant neoplasia mimicking pyogenic osteodiscitis.

Malignant neoplasia involving contiguous vertebrae and the corresponding intervertebral discs is a rare occurrence that has similar imaging manifestations as pyogenic osteodiscitis. The authors describe the imaging manifestations of two cases of malignant neoplasia mimicking pyogenic osteodiscitis. We present a case of an 83-year-old male with metastatic non-small cell lung carcinoma and an 82-year-old female with a plasmacytoma, both within the thoracic spine. These cases illustrate how the imaging features of pyogenic osteodiscitis may parallel those of malignant neoplasia.

Median palatine cyst.

Median palatine cysts are rare, non-odontogenic fissural cysts of the hard palate. These cysts occur in the midline of the hard palate, behind the incisive canal. Only two case reports have documented these cysts on multi-detector computed tomography (MDCT), neither giving detailed descriptions of the cysts. Knowledge of their existence is important and should not be confused with malignant tumors. We present the first case describing the MDCT characteristics of the median palatine cyst.