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Biomedical subjects

Kamalesh K Sirkar

Publications and source records attributed to Kamalesh K Sirkar.

5 recordsLinked to original sources

In vitro delivery of doxycycline hydrochloride based on a porous membrane-based aqueous-organic partitioning system.

This work investigated the controlled release of an antibiotic drug, doxycycline HCl, from its solution/suspension in an organic solvent in a reservoir through a porous membrane employing aqueous-organic partitioning with or without a mouse skin to simulate a skin patch. The reservoir contained the agent in solution in the solvent 1-octanol or its dispersion/solution in the solvent mineral oil with or without an enhancer. The porous membranes employed with water-in-pores were hydrophobic Celgard 2400 of polypropylene and hydrophilized polyvinylidene fluoride (PVDF). Conventional Franz diffusion cells as well as a skin patch were used. The transport rates of the agent observed through both Celgard and PVDF membranes could be successfully described by Fickian diffusion through the water-filled pores when the appropriate organic-aqueous partition coefficient was incorporated. The light mineral oil-based system yielded much higher permeability due to the much lower organic-aqueous partition coefficient of the antibiotic in light mineral oil. The optimized skin patch systems yielded drug flux and permeability values similar to their relevant membrane systems. The addition of a mouse skin beneath the patch drastically reduced the drug transfer rate. Among a number of enhancers used to correct this deficiency, linoleic acid at 10% level in the reservoir solution was found to yield a flux of 2.7 +/- 0.5 microg/cm(2) h and a permeability of 2.7e - 04 +/- 5.0e - 05 cm/h. These values are higher than the values available in literature obtained with full thickness human cadaver skin.

Alzheimer Disease↗

Highly selective membranes in protein ultrafiltration.

A new ultrafiltration technique based on a multimembrane stack has been developed to fractionate solutes closer in size than conventionally possible. The technique is illustrated here by obtaining a pure protein product from a binary protein mixture. By employing membranes in series without any gaskets or spacers in-between, ultrafiltration is carried out to separate two proteins relatively close in molecular weight or size. Flat YM30 regenerated cellulose membranes, all of the same molecular weight cut-off (MWCO) 30,000, are stacked together in the desired number, and ultrafiltration takes place. The membrane rejection of a protein is amplified with each additional membrane, ultimately resulting in a completely rejected species. Complete purification of the more permeable protein may be achieved regardless of the physicochemical condition that may be optimal or suboptimal for selective separation by a single membrane. Two systems, myoglobin and beta-lactoglobulin, as well as myoglobin and alpha-lactalbumin were studied, under various operating conditions. The solvent flux reduction encountered when each membrane is added may also be avoided, by operating at increased pressure, while still achieving the desired purification. Cleaning in situ is achievable with reproducible experimental results before and after on-line cleaning. The results clearly demonstrate that multimembrane stacks can be used for fractionation of proteins that are quite close in molecular weight/size.

Biotechnology↗

Protein loading, elution, and resolution behavior in a novel device that integrates ultrafiltration and chromatographic separation.

Hollow fiber membranes and chromatographic resin beads are commonly employed in a variety of bioseparation processes. A new class of integrated separation devices is being studied in which the shell side of a hollow fiber device is filled with adsorbents/chromatographic resin beads. Such devices and the corresponding separation methods integrate feed broth clarification by the microfiltration/ultrafiltration membrane with bioproduct purification by the shell-side resin beads either as an adsorbent or as beads in elution chromatography. A mathematical model has been developed for the prediction of the chromatographic behavior of such an integrated device. Simulations have been done to study the effects of axial dispersion, feed flow rate, water permeation rate, fiber packing density, and void fraction. Numerical solutions were obtained by solving the governing equations. This model can reasonably describe the concentration profiles as well as the breakthrough and elution behaviors in the integrated device.

Anion Exchange Resins↗

Stable liquid membranes: recent developments and future directions.

Immobilized liquid membranes offer the advantages of high selectivity and species flux in separation of species from either gaseous or liquid streams. Despite these advantages, they are not yet commercially viable because of their instabilities and limited lifetime. This paper presents recent advances made in developing stable immobilized liquid membranes for gas separation with high fluxes and selectivities for the species of interest. Some of the recent approaches being studied for development of stable liquid membranes for liquid separation are also discussed.

Chemistry Techniques, Analytical↗

A new integrated membrane filtration and chromatographic device.

To improve protein separation, a novel integrated device combining membrane filtration and chromatography has been developed. The device basically consists of a hollow fiber filtration module whose shell side is filled with chromatographic resin beads. However, there is an essentially impermeable coated zone near the hollow fiber module outlet. The integrated device enjoys the advantages of both membrane filtration and chromatography; it also allows one to load the chromatographic media directly from the fermentation broth or lysate and separate the adsorbed proteins through the subsequent elution step in a cyclic process. Interfacial polymerization was carried out to coat the bottom section of the hollow fiber membrane; the rest of the hollow fiber membrane remained unaffected. Myoglobin (Mb) and alpha-lactalbumin (alpha-LA) were primarily used as model proteins in a binary mixture; binary mixtures of Mb and bovine serum albumin (BSA) were also investigated. Separation behaviors of binary protein mixtures were studied in devices having either an ultrafiltration (UF) or a microfiltration (MF) membrane. Experimental results show that the breakthrough time and the protein loading capacities were dramatically improved after introducing the impermeable coating in both UF and MF modules. For a synthetic yeast fermentation broth feed, four loading-washing-elution-reequilibration-based cyclic runs for separation of Mb and alpha-LA were performed in the device using a MF membrane with a coated zone without cleaning in between. The Mb and alpha-LA elution profiles for the four consecutive runs were almost superimposable. Due to lower transmembrane flux in this device plus the periodical washing-elution during the chromatographic separation, fouling was not a problem, unlike in conventional microfiltration.

Chromatography, Liquid↗