-
Mcintosh Michelsen posted an update 1 year, 5 months ago
A rolling CRR, calculated using the last 100 samples, is a good compromise between reliability of the CRR value and timely prediction of process changes.The present investigation aimed to develop curcumin loaded turmeric oil microemulsion for brain targeting. An effort has been made to investigate the role of functional components in developing brain targeted formulation which could enhance the bioavailability and uptake of drug in the brain upon oral administration. Preliminary studies like solubility study, emulsification study and construction of the pseudo ternary phase diagram were performed for screening components. The formulation was optimized by using extreme vertices mixture design. The optimized formulation was characterized for appearance, stability to centrifugation, dilution potential, globule size, zeta potential and drug content. Furthermore, ex-vivo permeation in chicken gut sac non everted technique and pharmacokinetic study in adult zebra fishes were carried out. The optimized formulation was found to clear, yellow-colored with the absence of phase separation and precipitation denoted the stability of formulation to centrifugation and dilution. The mean globule size, polydispersity index, zeta potential and drug content was observed as 29.13± 0.12 nm, 0.23 ± 0.01,-12.33 ± 1.37 mV and 99.10±3.91 %, respectively. Ex vivo permeation study revealed 2.41 fold enhancement in the steady-state flux when compared to curcumin solution. Furthermore, optimized formulation showed shorter Tmax (5 min) and higher AUC(0-∞) (7.93 μg/brain*min) compared to the curcumin solution which showed similar Tmax and AUC(0-∞) of 2.78 μg/brain*min after oral administration to zebra fishes revealing 3.97 fold enhancement. The results revealed enhanced ex vivo oral absorption and enhanced in vivo brain pharmacokinetics of curcumin via functional microemulsion in the zebra fish model.Recent evidence suggests that comorbidities between neuropsychiatric conditions and metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medication, such as a higher risk of type 2 diabetes and cardiovascular disease, which result in increased mortality. In the present study we compare the expression of key metabolic proteins, including the insulin receptor (CD220), glucose transporter 1 (GLUT1) and fatty acid translocase (CD36), on peripheral blood mononuclear cell subtypes from patients across the neuropsychiatric spectrum, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions (n = 25/condition), relative to typical controls (n = 100). This revealed alterations in the expression of these proteins that were specific to schizophrenia. Further characterization of metabolic alterations in an extended cohort of first-onset antipsychotic drug-naïve schizophrenia patients (n = 58) and controls (n = 63) revealed that the relationship between insulin receptor expression in monocytes and physiological insulin sensitivity was disrupted in schizophrenia and that altered expression of the insulin receptor was associated with whole genome polygenic risk scores for schizophrenia. Finally, longitudinal follow-up of the schizophrenia patients over the course of antipsychotic drug treatment revealed that peripheral metabolic markers predicted changes in psychopathology and the principal side effect of weight gain at clinically relevant time points. Gefitinib clinical trial These findings suggest that peripheral blood cells can provide an accessible surrogate model for metabolic alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic complications following antipsychotic therapy.In honor of Prof. Thorsteinn Loftsson’s 70th birthday, we offer this personal review of our work using cyclodextrins (CDs) complexed with a variety of active ingredients, including pharmaceuticals, for the purpose of improving their delivery to polymer materials, e.g., fibers, films, hydrogels, etc. Using the affinity of CDs to host and form non-covalent inclusion complexes (ICs) with guest molecules, including a variety of high molecular weight polymers, it is possible to readily deliver these guest molecules into polymer materials via either melt or solution processing of their crystalline or soluble guest molecule-CD-ICs or -rotaxanes. This provides the following advantages i. CDs are non-toxic, implantable, and biodegradable and have earned the GRAS rating from the FDA. ii. Guest molecules, even those that are neat liquids, can form solid crystalline CD-ICs that are thermally stable to ~ 200 °C and above. This approach permits facile melt-processing into polymer materials for delivery without migration, llymer materials.The potential of alternative routes of application compared to the traditional oral route is constantly growing. Especially in transmucosal applications for the oral cavity, easy accessibility is an attractive feature with many new opportunities. The combination of a minitablet and a buccal mucoadhesive carrier film has been shown to enable safe and accurate drug administration compared to semi-solid formulations currently available on the market. In order to investigate these so-called composite dosage forms in more detail, two different manufacturing methods were compared within this study to investigate the resulting properties. The formulation development of the minitablets containing lidocaine, complying with the compendial requirements, resulted in immediate release using both manufacturing methods (more than 80% lidocaine release after 3-4 min using direct incorporation, 7-8 min by the gluing method). Differences in morphology and drug migration behaviour could be observed. The directly incorporated minitablets revealed a twofold higher drug migration (1.5 mm) into the mucoadhesive shielding film within two weeks compared to the glued minitablets (0.8 mm). These findings enable a further optimization of the formulation depending on the duration of the application and the feasibility for the addressed patient population.

