Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.     

Multi-Trip Time-Dependent Vehicle Routing Problem with Soft Time Windows and Overtime Constraints

Networks and Spatial Economics - The multi-trip time-dependent vehicle routing problem with soft time windows and overtime constraints (MT-TDVRPSTW-OT) is considered in this paper. The modified...     

Branch-and-Bound-Based Local Search Heuristics for Train Timetabling on Single-Track Railway Network

The modified formulation and two branch-and-bound-based local search heuristic algorithms for train timetabling in single-track railway network in the planning application are proposed. The original local search heuristic is modified such that when a neighbor of a currently tested resolved conflict for improvement is evaluated, the depth-first search branch-and-bound algorithm is employed with two branching rules: least-lower-bound and least-delay-time. The detailed implementation of the proposed heuristic algorithms are described, including the neighborhood definitions of overtaking and crossing conflicts, the procedure to detect overtaking and crossing conflicts, and a recursive procedure for the depth-first search branch-and-bound algorithm. The proposed heuristic algorithms, the original heuristic, the equivalent manual solution method and the exact solution method are compared using a toy problem and four problems (26-train, 50-train, 76-train and 108-train) in the Thailand Southern line railway network, which consisted of 266 single-track segments, 15 double-track segments, 282 stations/sidings, and total distance of 1577 km. The proposed heuristic algorithm with the least-lower-bound branching rule outperforms the other heuristics in terms of the solution quality with up to 2.827 % improvement over the equivalent manual solution method and less than 8 % optimality gap. The proposed heuristic algorithms require longer time to terminate than the original heuristic. The proposed heuristic algorithm with the least-lower-bound branching rule converges faster than that with the least-delay-time branching rule in all test problems. Based on the empirical results, the proposed heuristic algorithms are solvable in polynomial time. Furthermore, the proposed heuristic algorithm with the least-lower-bound branching rule is enhanced by embedding a uniform sampling strategy, and it is found that the total CPU time can be saved by about 50 % with marginally worse solution quality.     

Integrated Network Capacity Expansion and Traffic Signal Optimization Problem: Robust Bi-level Dynamic Formulation

This paper presents a robust optimization formulation, with an exact solution method, that simultaneously solves continuous network capacity expansion, traffic signal optimization and dynamic traffic assignment when explicitly accounting for an appropriate robustness measure, the inherent bi-level nature of the problem and long-term O-D demand uncertainty. The adopted robustness measure is the weighted sum of expected total system travel time (TSTT) and squared up-side deviation from a fixed target. The model propagates traffic according to Daganzo’s cell transmission model. Furthermore, we formulate five additional, related models. We find that when evaluated in terms of robustness, the integrated robust model performs the best, and interestingly the sequential robust approach yields a worse solution compared to certain sequential and integrated approaches. Although the adopted objective of the integrated robust model does not directly optimize the variance of TSTT, our experimental results show that the robust solutions also yield the least-variance solutions.     

A Dantzig-Wolfe Decomposition Based Heuristic Scheme for Bi-level Dynamic Network Design Problem

We present a heuristic to solve the NP-hard bi-level network design problem (NDP). The heuristic is developed based on the Dantzig-Wolfe decomposition principle such that it iteratively solves a master problem and a pricing problem. The master problem is the budget allocation linear program solved by CPLEX to determine the budget allocation and construct a modified cell transmission network for the pricing problem. The pricing problem is the user-optimal dynamic traffic assignment (UODTA) solved by an existing combinatorial algorithm. To facilitate the decomposition principle, we propose a backward connectivity algorithm and complementary slackness procedures to efficiently approximate the required dual variables from the UODTA solution. The dual variables are then employed to augment a new column in the master program in each iteration. The iterative process repeats until a stopping criterion is met. Numerical experiments are conducted on two test networks. Encouraging results demonstrate the applicability of the heuristic scheme on solving large-scale NDP. Though a single destination problem is considered in this paper, the proposed scheme can be extended to solve multi-destination problems as well.     

Effect of Grinding of β-Cyclodextrin and Glibenclamide on Tablet Properties. Part I. in vitro

Physical properties including dissolution characteristics of glibenclamide (GB) tablets were studied. Directly compressed and wet-granulated GB tablets gave only 35% and 40% drug dissolved, respectively. Physical mixing, kneading, and grinding of β-cyclodextrin (CD) with GB were investigated. It was found that the grinding method could markedly enhance the release of drug from the tablets. The physical properties of these tablets were unchanged after they had been stored at 40°C and 75% RH for at least 3 months. The GBKD mixture at a ratio of 1 to 4, ground for 24 or 48 hr, exhibited superior dissolution and chemical stability. Differential scanning calorimetry indicated that an inclusion complex was produced. Decreasing grinding time or CD concentration could result in incomplete formation of the inclusion complex. It was concluded that pretreatment of the drug with CD by the grinding method could significantly improve the dissolution and stability of GB tablets.     

Time‐Varying Lane‐Based Capacity Reversibility for Traffic Management

Abstract: This article presents a new bi‐level formulation for time‐varying lane‐based capacity reversibility problem for traffic management. The problem is formulated as a bi‐level program where the lower level is the cell‐transmission‐based user‐optimal dynamic traffic assignment (UODTA). Due to its Non‐deterministic Polynomial‐time hard (NP‐hard) complexity, the genetic algorithm (GA) with the simulation‐based UODTA is adopted to solve multiorigin multidestination problems. Four GA variations are proposed. GA1 is a simple GA. GA2, GA3, and GA4 with a jam‐density factor parameter (JDF) employ time‐dependent congestion measures in their decoding procedures. The four algorithms are empirically tested on a grid network and compared based on solution quality, convergence speed, and central processing unit (CPU) time. GA3 with JDF of 0.6 appears best on the three criteria. On the Sioux Falls network, GA3 with JDF of 0.7 performs best. The GA with the appropriate inclusion of problem‐specific knowledge and parameter calibration indeed provides excellent results when compared with the simple GA.     

Efficient Insertion Heuristic Algorithms for Multi-Trip Inventory Routing Problem with Time Windows,Shift Time Limits and Variable Delivery Time

Networks and Spatial Economics - Efficient insertion heuristic algorithms allowing multi trips per vehicle (EIH-MT) and allowing a single trip per vehicle with post-processing greedy heuristic...     

Development of phyllanthin-loaded self-microemulsifying drug delivery system for oral bioavailability enhancement

Phyllanthin, a poorly water-soluble herbal active component from Phyllanthus amarus, exhibited a low oral bioavailability. This study aims at formulating self-microemulsifying drug delivery systems (SMEDDS) containing phyllanthin and evaluating their in-vitro and in-vivo performances. Excipient screening was carried out to select oil, surfactant and co-surfactant. Formulation development was based on pseudo-ternary phase diagrams and characteristics of resultant microemulsions. Influences of dilution, pH of media and phyllanthin content on droplet size of the resultant emulsions were studied. The optimized phyllanthin-loaded SMEDDS formulation (phy-SMEDDS) and the resultant microemulsions were characterized by viscosity, self-emulsification performance, stability, morphology, droplet size, polydispersity index and zeta potential. In-vitro dissolution and oral bioavailability in rats of phy-SMEDDS were studied and compared with those of plain phyllanthin. Phy-SMEDDS consisted of phyllanthin/Capryol 90/Cremophor RH 40/Transcutol P (1.38:39.45:44.38:14.79) in % w/w. Phy-SMEDDS could be emulsified completely within 6?min and formed fine microemulsions, with average droplet range of 27–42?nm. Phy-SMEDDS was robust to dilution and pH of dilution media while the resultant emulsion showed no phase separation or drug precipitation after 8?h dilution. The release of phyllanthin from phy-SMEDDS capsule was significantly faster than that of plain phyllanthin capsule irrespective of pH of dissolution media. Phy-SMEDDS was found to be stable for at least 6 months under accelerated condition. Oral absorption of phyllanthin in rats was significantly enhanced by SMEDDS as compared with plain phyllanthin. Our study indicated that SMEDDS for oral delivery of phyllanthin could be an option to enhance its bioavailability.