Formulation and Stability Study of Eslicarbazepine Acetate Oral Suspensions for Extemporaneous Compounding

Eslicarbazepine acetate is an anticonvulsant drug with a recent U.S. Food and Drug Administration approval for expanded use in children and adolescents. Currently, eslicarbazepine acetate is only available in the U.S. as 200-mg to 800-mg strength tablets (Aptiom), which are not easy to administer for pediatric patients. This study was initiated to develop an oral suspension formulation for extemporaneous compounding by pharmacists and to generate stability data for storage recommendations. Nine suspension formulations of eslicarbazepine acetate were prepared from Aptiom tablets and commercially available liquid vehicles using the standard mortar/pestle method. The vehicles varied mainly in their solvents, viscosities, and sweeteners. The formulations were evaluated for ease of preparation, physical properties, and initial potency. Two lead formulations were selected for a two-month stability study at room temperature or under refrigeration (2°C to 8°C). The stability samples were withdrawn at pre-determined time points and analyzed by visual inspection, pH measurement, and a stability-indicating high-performance liquid chromatographic assay. The majority of the 9 formulations were found to be easy to prepare and administer at a concentration of 40-mg/mL eslicarbazepine acetate. Particle settling was observed in several formulations over time, but they were re-suspended satisfactorily upon shaking. Two suspensions in 50:50 v/v mixtures of Ora-Sweet or Ora-Sweet SF with Ora-Plus were selected as the lead formulations for the two-month stability study. At the initiation of the study, all samples appeared as white and smooth suspensions with pH ranging from 4.39 to 4.46. The high-performance liquid chromatographic results confirmed that the initial samples contained 100.4% to 102.2% of the label claim strength. Over two months of storage at room temperature or refrigeration, there were no significant changes in visual appearance, re-suspendability, pH, or potency for any samples. No new degradation peaks were observed in any highperformance liquid chromatograms. Based on the study results, two eslicarbazepine acetate suspensions are recommended for extemporaneous compounding from Aptiom tablets. The formulations consist of 40 mg/mL eslicarbazepine acetate in 50:50 v/v Ora-Sweet:Ora-Plus or Ora-Sweet SF:Ora-Plus. Once prepared, these suspensions can be stored at room temperature or under refrigeration for up to two months

Minimum-cost multicast over coded packet networks

We consider the problem of establishing minimum-cost multicast connections over coded packet networks, i.e., packet networks where the contents of outgoing packets are arbitrary, causal functions of the contents of received packets. We consider both wireline and wireless packet networks as well as both static multicast (where membership of the multicast group remains constant for the duration of the connection) and dynamic multicast (where membership of the multicast group changes in time, with nodes joining and leaving the group). For static multicast, we reduce the problem to a polynomial-time solvable optimization problem, and we present decentralized algorithms for solving it. These algorithms, when coupled with existing decentralized schemes for constructing network codes, yield a fully decentralized approach for achieving minimum-cost multicast. By contrast, establishing minimum-cost static multicast connections over routed packet networks is a very difficult problem even using centralized computation, except in the special cases of unicast and broadcast connections. For dynamic multicast, we reduce the problem to a dynamic programming problem and apply the theory of dynamic programming to suggest how it may be solved

Regulation of Obesity and Metabolic Complications by Gamma and Delta Tocotrienols

Tocotrienols (T3s) are a subclass of unsaturated vitamin E that have been extensively studied for their anti-proliferative, anti-oxidative and anti-inflammatory properties in numerous cancer studies. Recently, T3s have received increasing attention due to their previously unrecognized property to attenuate obesity and its associated metabolic complications. In this review, we comprehensively evaluated the recent published scientific literature about the influence of T3s on obesity, with a particular emphasis on the signaling pathways involved. T3s have been demonstrated in animal models or human subjects to reduce fat mass, body weight, plasma concentrations of free fatty acid, triglycerides and cholesterol, as well as to improve glucose and insulin tolerance. Their mechanisms of action in adipose tissue mainly include (1) modulation of fat cell adipogenesis and differentiation; (2) modulation of energy sensing; (3) induction of apoptosis in preadipocytes and (4) modulation of inflammation. Studies have also been conducted to investigate the effects of T3s on other targets, e.g., the immune system, liver, muscle, pancreas and bone. Since δT3 and γT3 are regarded as the most active isomers among T3s, their clinical relevance to reduce obesity should be investigated in human trials

The Design of a Sterile Product Laboratory Module as Preparation for an Institutional IPPE Course

Objectives: To develop a pharmaceutics laboratory module on compounded sterile products for the second year pharmacy students as preparation for an institutional pharmacy experiential course. Method: A 5-week lab module was designed and implemented as part of the Pharmaceutics Lab Course to provide training in the basic skills of sterile product compounding. The module included techniques in the handling of sterile products, aseptic techniques, medium risk products, and hazardous products. A practical exam was given at the end of this module to ensure student competency. Upon completion of the lab module, students enrolled in a required 4-week institutional pharmacy experiential course (IPPE-2), where students were required to compound a minimum of 10 sterile products. Students were then asked to participate in a survey assessing the effectiveness and relevance of the lab module as preparation for their IPPE-2. Results: The sterile product lab module was offered in the spring semester with 75 students enrolled. All students passed the sterile product lab module and continued onto the IPPE-2 course during the following summer. The student survey indicated that the students felt well prepared for the IPPE-2 and that the preceptors were satisfied with their prior training in sterile compounding. The average scores ranged from 4.8 - 6.5 (scale of 1-7) for the various products addressed in the lab module. Implications: The 5-week sterile product lab module progressively prepares the students with the basic skills and knowledge in compounding sterile products. This preparedness allows the students to transition smoothly into the subsequent institutional pharmacy experiential course. Copyright © 2011 American Association of Colleges of Pharmac

A novel multi-objective evolutionary algorithm based on space partitioning

To design an e ective multi-objective optimization evolutionary algorithms (MOEA), we need to address the following issues: 1) the sensitivity to the shape of true Pareto front (PF) on decomposition-based MOEAs; 2) the loss of diversity due to paying so much attention to the convergence on domination-based MOEAs; 3) the curse of dimensionality for many-objective optimization problems on grid-based MOEAs. This paper proposes an MOEA based on space partitioning (MOEA-SP) to address the above issues. In MOEA-SP, subspaces, partitioned by a k-dimensional tree (kd-tree), are sorted according to a bi-indicator criterion de ned in this paper. Subspace-oriented and Max-Min selection methods are introduced to increase selection pressure and maintain diversity, respectively. Experimental studies show that MOEA-SP outperforms several compared algorithms on a set of benchmarks

Synchronous multi-decadal climate variability of the whole Pacific areas revealed in tree rings since 1567

Oceanic and atmospheric patterns play a crucial role in modulating climate variability from interannual to multi-decadal timescales by causing large-scale co-varying climate changes. The brevity of the existing instrumental records hinders the ability to recognize climate patterns before the industrial era, which can be alleviated using proxies. Unfortunately, proxy based reconstructions of oceanic and atmospheric modes of the past millennia often have modest agreements with each other before the instrumental period, raising questions about the robustness of the reconstructions. To ensure the stability of climate signals in proxy data through time, we first identified tree-ring datasets from distant regions containing coherent variations in Asia and North America, and then interpreted their climate information. We found that the multi-decadal covarying climate patterns of the middle and high latitudinal regions around the northern Pacific Ocean agreed quite well with the climate reconstructions of the tropical and southern Pacific areas. This indicates a synchronous variability at the multi-decadal timescale of the past 430 years for the entire Pacific Ocean. This pattern is closely linked to the dominant mode of the Pacific sea surface temperature (SST) after removing the warming trend. This Pacific multi-decadal SST variability resembles the Interdecadal Pacific Oscillation

Sphingosine-1-phosphate promotes the differentiation of human umbilical cord mesenchymal stem cells into cardiomyocytes under the designated culturing conditions

<p>Abstract</p> <p>Background</p> <p>It is of growing interest to develop novel approaches to initiate differentiation of mesenchymal stem cells (MSCs) into cardiomyocytes. The purpose of this investigation was to determine if Sphingosine-1-phosphate (S1P), a native circulating bioactive lipid metabolite, plays a role in differentiation of human umbilical cord mesenchymal stem cells (HUMSCs) into cardiomyocytes. We also developed an engineered cell sheet from these HUMSCs derived cardiomyocytes by using a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm) cell sheet technology.</p> <p>Methods</p> <p>Cardiomyogenic differentiation of HUMSCs was performed by culturing these cells with either designated cardiomyocytes conditioned medium (CMCM) alone, or with 1 μM S1P; or DMEM with 10% FBS + 1 μM S1P. Cardiomyogenic differentiation was determined by immunocytochemical analysis of expression of cardiomyocyte markers and patch clamping recording of the action potential.</p> <p>Results</p> <p>A cardiomyocyte-like morphology and the expression of α-actinin and myosin heavy chain (MHC) proteins can be observed in both CMCM culturing or CMCM+S1P culturing groups after 5 days' culturing, however, only the cells in CMCM+S1P culture condition present cardiomyocyte-like action potential and voltage gated currents. A new approach was used to form PIPAAm based temperature-responsive culture surfaces and this successfully produced cell sheets from HUMSCs derived cardiomyocytes.</p> <p>Conclusions</p> <p>This study for the first time demonstrates that S1P potentiates differentiation of HUMSCs towards functional cardiomyocytes under the designated culture conditions. Our engineered cell sheets may provide a potential for clinically applicable myocardial tissues should promote cardiac tissue engineering research.</p