Development and Evaluation of Self-Microemulsifying Drug Delivery System for Improving Oral Absorption of Poorly Water-Soluble Olaparib.

The purpose of this study is to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) to improve the oral absorption of poorly water-soluble olaparib. Through the solubility test of olaparib in various oils, surfactants and co-surfactants, pharmaceutical excipients were selected. Self-emulsifying regions were identified by mixing the selected materials at various ratios, and a pseudoternary phase diagram was constructed by synthesizing these results. The various physicochemical properties of microemulsion incorporating olaparib were confirmed by investigating the morphology, particle size, zeta potential, drug content and stability. In addition, the improved dissolution and absorption of olaparib were also confirmed through a dissolution test and a pharmacokinetic study. An optimal microemulsion was generated in the formulation of Capmul® MCM 10%, Labrasol® 80% and PEG 400 10%. The fabricated microemulsions were well-dispersed in aqueous solutions, and it was also confirmed that they were maintained well without any problems of physical or chemical stability. The dissolution profiles of olaparib were significantly improved compared to the value of powder. Associated with the high dissolutions of olaparib, the pharmacokinetic parameters were also greatly improved. Taken together with the results mentioned above, the microemulsion could be an effective tool as a formulation for olaparib and other similar drugs.

Effects of Local Anesthetics With or Without Steroids in High-Volume Transforaminal Epidural Blocks for Lumbar Disc Herniation: A Randomized, Double-Blind, Controlled Trial.

BACKGROUND: Lumbar transforaminal epidural block (TFEB) is an effective treatment modality for radicular pain due to lumbar disc herniation (LDH). The addition of steroids is more effective than local anesthetic alone in TFEBs for patients with LDH. Moreover, the efficacy of TFEBs has been reported to be positively correlated with the volume of injectate. We hypothesized that high-volume TFEBs without steroids effectively alleviate axial back and radicular pain associated with LDH. This study compared the efficacy of high-volume TFEBs with vs. without steroids for the management of the axial and radicular pain caused by LDH. METHODS: A total of 54 patients were randomly assigned to either group L or group D. Patients in group L received 8-mL injections of 0.33% lidocaine only. Patients in group D received 8-mL injections of 0.33% lidocaine with 5 mg of dexamethasone. The primary outcomes were pain intensity at baseline and 4 weeks after the procedure. The secondary outcomes included the change of functional disability between baseline and 4 weeks after the procedure, pain scores during injection, and adverse effects. RESULTS: Both groups showed a significant reduction in axial and radicular pain and improvement in the functional status at the outpatient visit 4 weeks after TFEB. However, there were no significant differences between the groups in terms of changes in back pain (10.00 [20.00] vs. 10.00 [22.50]; P = 0.896) or radicular pain (5.00 [20.00] vs. 10.00 [12.50]; P = 0.871). CONCLUSION: High-volume TFEBs with and without steroid administration yielded similar significant pain reductions and functional improvements among LDH patients 4 weeks after the procedure.

Epidural blood patch for spontaneous intracranial hypotension with subdural hematoma: A case report and review of literature.

BACKGROUND: Cerebrospinal fluid (CSF) leakage at C1/2 in spontaneous intracranial hypotension (SIH) is rare. Subdural hematoma (SDH), a serious complication of SIH, may lead to neurological deficits. This report presents a case of SDH after spontaneous C1/2 CSF leakage, which was treated with a targeted epidural blood patch (EBP). CASE SUMMARY: A 60-year-old man with no history of trauma was admitted to our hospital with orthostatic headache, nausea, and vomiting. Brain computed tomography imaging revealed bilateral, subacute to chronic SDH. Brain magnetic resonance imaging (MRI) findings were SDH with dural enhancement in the bilateral cerebral convexity and posterior fossa and mild sagging, suggesting SIH. Although the patient underwent burr hole trephination, the patient's orthostatic headache was aggravated. MR myelography led to a suspicion of CSF leakage at C1/2. Therefore, we performed a targeted cervical EBP using an epidural catheter under fluoroscopic guidance. At 5 d after EBP, a follow-up MR myelography revealed a decrease in the interval size of the CSF collected. Although his symptoms improved, the patient still complained of headaches; therefore, we repeated the targeted cervical EBP 6 d after the initial EBP. Subsequently, his headache had almost disappeared on the 8th day after the repeated EBP. CONCLUSION: Targeted EBP is an effective treatment for SDH in patients with SIH due to CSF leakage at C1/2.

Surface Activity and Emulsifying Effect of Non-Toxic Starch Nanocrystal.

The purpose of this study is to investigate the surface activity of starch nanocrystals (SNC), material derived from starch, and confirm their usefulness as a surfactant. In order to evaluate the surface activity, the surface tension change of suspended SNC solution via the Wilhelmy plate method was measured and the values were compared with various synthetic surfactants. The effect of SNC as emulsifier was evaluated on emulsion formation and physical stability. The surface tension of the SNC-dispersed solution was decreased while its concentration was increased. When the 5.0% (w/v) of SNC was added, the surface tension was decreased from 70.3 to 49.5 mN/m. It was confirmed that the physical stability of the emulsion prepared by adding the SNC was improved compared to that of surface inactivity material (PEG 400). The phase separation was observed within 1 hour after preparation of the emulsion containing PEG 400, but the emulsion containing SNC was stable for 5 hours or more. To summarize this study, SNC, a natural-derived and non-toxic material, exhibits sufficient surface activity, thereby confirming the possibility of being applied to the food and pharmaceutical industry.

Preparation and Evaluation of Nanostructured Lipid Carrier for Topical Delivery of Velutin: Synthetic Tyrosinase Inhibitor.

The purpose of this study is to produce nanostructured lipid carrier (NLC) that can solubilize poorly water-soluble velutin and verify an improved tyrosinase synthesis inhibition. A solubility test for velutin was conducted. Cetyl palmitate and caprylic/capric triglyceride were selected as solubilizer. The lipid matrix was produced using the ultrasound dispersion method. The morphology and size distribution of the produced NLC was analyzed through scanning electron microscopy (SEM) and dynamic light scattering (DLS), and the release and tyrosinase inhibition of velutin was evaluated through the Franz diffusion cell method and tyrosinase inhibition assay. Lipid matrix nanoparticles showed an average size of approximately 250 nm and polydispersity of 0.2, and it was confirmed that the velutin incorporated within nanoparticles sustained release at a constant rate over 36 hours. Due to extremely low aqueous solubility, the tyrosinase synthesis inhibition of velutin suspension was 0%, and the value of velutin incorporated within the NLC formulation was greatly improved 56.5% (40 µg/mL). As a result, it was verified that lipid-based NLC nanoparticles are an efficient formulation for the topical delivery of poorly water-soluble flavonoids such as velutin.