Alternative Granulation Technique: Melt Granulation

A melt granulation process has been investigated (1, 2) which efficiently agglomerates pharmaceutical powders for use in both immediate- and sustained-release solid dosage forms. The process utilizes materials that are effective as granulating fluids when they are in the molten state. Cooling of the agglomerated powders and the resultant solidification of the molten materials completes the granulation process. Both the molten agglomeration and cooling solidification were accomplished in a high shear Collette Gral mixer equipped with a jacketed bowl. Hence, the melt granulation process replaces the conventional granulation and drying operations which use water or alcohol solutions. The melt granulation process has been investigated using immediate- and sustained-release TAVIST® (clemastine fumarate USP) tablet formulations. The TAVIST granulations have been characterized by power consumption monitoring, measurement of the granulation particle size distribution, bulk and tapped density determinations, and loss-on-drying measurements. Scale-up of the melt granulation process for the sustained release TAVIST tablet formulation was judged successful based on a comparison of the hardness, friability, weight uniformity during compression, disintegration time, and dissolution rate data obtained at different manufacturing scales.     

Development of manufacturing control strategies using unsupervised machine learning

This research considers the control of manufacturing systems that support job routing and process sequence flexibility. A machine learning system is presented that uses a simulation model of the target manufacturing system to discover opportunistic control rules. Learning is unsupervised and is driven by a genetic algorithm. The learning method requires very little a priori control knowledge. For this presentation, the decision-making agents are the part types being processed. Part types evolve cooperative strategies for selecting the best route through the manufacturing system based on simulated real-time information that describes the state of the system. Results are presented that demonstrate the effectiveness of the approach.     

Observation and Modeling of a Room-Temperature Negative Characteristic Temperature 1.3-μm p-Type Modulation-Doped Quantum-Dot Laser

A room-temperature negative characteristic temperature (T₀ ) and ultralow threshold current density (J_th) of 48 Amiddotcm^-2 are demonstrated for a 1.3-mum InAs quantum dot laser. These characteristics are obtained by combining a high-growth-temperature GaAs spacer layer with p-type modulation doping of the quantum dots in multiple layer dot-in-a-well structures. Through a comparison of p-doped and undoped devices, a photon coupling mechanism is proposed to account for the different temperature dependences of Jth for the two devices. Numerical simulations based on a rate equation model, which includes photon coupling between ground and excited quantum dot states, are performed. The simulations are able to account for the very different temperature-dependent Jth behavior of the doped and undoped device     

DNA binding of an ethidium intercalator attached to a monolayer-protected gold cluster

Ethidium intercalation has been investigated as a means of inducing binding of Au nanoparticles to DNA. The ethidium sites are attached to the nanoparticles as thiolate ligands, using 3,8-diamino-5-mercaptododecyl-6-phenylphenanthridinium (ethidium thiolate). Each nanoparticle bears only one or two ethidium thiolate ligands. The rest of the thiolate monolayer ligands on the monolayer-protected Au clusters (MPCs) were either N-(2-mercaptopropionyl)glycine (tiopronin/ethidium MPC) or trimethyl(mercaptoundecyl)ammonium (TMA/ethidium MPC). In solution mixtures of DNA and MPCs, the energy-transfer quenching of the ethidium ligands by the metal-like MPC core is partially released by ethidium binding to DNA, as observed by an increase in the intensity of ethidium fluorescence. Binding of the cationic TMA/ethidium MPC to DNA was efficient and rapid. The negatively charged tiopronin/ethidium MPC, in contrast, exhibits slow intercalation kinetics, relative to ethidium cation not attached to an MPC. The slow kinetics were analyzed as two competing binding interactions. The tiopronin/ethidium MPC binding to DNA was imaged by AFM.     

Behavior-change trials to assess the feasibility of improving complementary feeding practices and micronutrient intake of infants in rural Bangladesh

This study used simple rapid-assessment techniques to test the feasibility of increasing the consumption of complementary foods by infants by asking mothers to increase meal quantity or frequency or by altering the viscosity/energy density of the food. The feasibility of using micronutrient supplements either added directly to food or administered as liquid drops was also examined. The study was conducted in rural Bangladesh and involved four separate short-term behavioral change trials. Depending on the trial, fieldworkers recruited 30 to 45 infants 6 to 12 months of age. Following recommendations to increase the amount of food provided to infants, the mean intakes from single meals increased from 40 +/- 23 g on day 1 to 64 +/- 30 g on day 7 (p < 0.05). In a second trial, the mean meal frequency increased from 2.2 +/- 1.3 on day 1 to 4.1 +/- 1.3 on day 7 (p < 0.05). Provision of high-energy-density diets, prepared by decreasing viscosity with alpha-amylase or by hand-mashing rice and dhal into a paste before feeding, increased single-meal energy consumption from 54 +/- 35 kcal to 79 +/- 52 kcal or 75 +/- 37 kcal (p < 0.05), respectively. Both types of micronutrient supplements were well accepted and used according to recommendations. In conclusion, it was possible to change short-term child-feeding behaviors to promote increased food intake, mealfrequency, energy density, and micronutrient consumption. Because each of these interventions lasted for only about 1 week, however, the long-term sustainability of these changes is not known. Moreover, the effect of increased feeding of complementary foods on intakes of breastmilk and total daily consumption of energy and nutrients requires further study.     

Treatment of African children with uncomplicated falciparum malaria with a new antimalarial drug, CGP 56697

New antimalarial drugs are urgently needed. The use of short courses of the new antimalarial drug artemether as monotherapy has been limited by secondary malaria episodes following parasite clearance. Therefore, a new antimalarial drug, CGP 56697, has been developed, which combines artemether with a longer-acting antimalarial agent, benflumetol. A safety trial was undertaken in 60 Gambian children 1-6 years old with uncomplicated Plasmodium falciparum malaria. All children treated with CGP 56697 cleared their parasites 72 h after the start of treatment. No neurologic, cardiac, or other adverse reactions were observed. Second episodes of falciparum malaria were recorded in 16 (27%) of the children. Second infections were more frequent during the rainy season than during the dry season. Molecular epidemiologic studies suggested that 12 of the 14 second episodes of malaria in children treated with CGP 56697 were due to new infections. CGP 56697 proved to be a safe and effective antimalarial drug in African children.     

Strip Yield Model Numerical Application to Different Geometries and Loading Conditions

A new numerical method based on the strip yield analysis approach was developed for calculating the Crack Tip Opening Displacement (CTOD). This approach can be applied to any crack geometry, of either infinite or finite extent, with arbitrary applied loading conditions. The technique is an adaptation of the dislocation-density based boundary element method to obtain crack-face opening displacements at any point on a crack, and succeeds in obtaining the requisite values as a series of definite integrals, the functional parts of each of which are evaluated exactly in closed form. The power of the technique is demonstrated by obtaining solutions to several crack configurations of practical interest.