Mahmut Seker

Freeze-Drying of Pharmaceutical Products: Research and Development Needs

Significance of pharmaceutical formulation (choosing of correct excipients in optimal quantities), effects of glass transition temperature, importance of theoretical modeling of the process, benefits of optimal control, and the advantages of remote monitoring of the process are presented. Experimental and theoretical research and development needs for the freeze-drying of pharmaceutical products are proposed and discussed.

Optimal Control of the Primary Drying Stage of Freeze Drying of Solutions in Vials Using Variational Calculus

Abstract The problem of operating freeze drying of pharmaceutical products in vials placed in trays of a freeze dryer to remove free water (in frozen state) at a minimum time was formulated as an optimal control problem. Two different types of freeze dryer designs were considered. In type I freeze dryer design, upper and lower plate temperatures were controlled together, while in type II freeze dryer design, upper and lower plate temperatures were controlled independently. The heat input to the material being dried and the drying chamber pressure were considered as control variables. Constraints were placed on the system state variables by the melting and scorch temperatures during primary drying stage. Necessary conditions of optimality for the primary drying stage of freeze drying process in vials are derived and presented. Furthermore, an approach for constructing the optimal control policies that would minimize the drying time for the primary drying stage was given. In order to analyze optimal control policy for the primary drying stage of the freeze-drying process in vials, a rigorous multi-dimensional unsteady state mathematical model was used. The theoretical approach presented in this work was applied in the freeze drying of skim milk. Significant reductions in the drying times of primary drying stage of freeze drying process in vials were obtained, as compared to the drying times obtained from conventional operational policies.

Cross‐Linking of Starch with Reactive Extrusion and Expansion of Extrudates

Abstract Starch was extruded in a single‐screw extruder with sodium hydroxide and three levels of sodium trimetaphosphate (STMP) as 5, 10, and 15% after moisture content was adjusted to 40%. The amount of phosphorus that was incorporated into starch during extrusion, paste viscosity, water solubility index, and sectional expansion index (SEI) of extrudates were determined. A pasting viscosity of phosphorylated starch showed that starch was cross‐linked with phosphorus that was incorporated into starch. The cross‐linking of starch with STMP and increasing the levels of STMP from 5 to 15% reduced the water solubility index and SEI of extrudates.

Phosphorus binding to starch during extrusion in both single- and twin-screw extruders with and without a mixing element

The effect of a mixing element in single- and twin-screw extruders on the amount of phosphorus incorporated into starch was investigated for chemical modification of starch that has applications in the food and paper industries. Starch was mixed with sodium hydroxide and sodium trimetaphosphate and then the mixture was extruded. Screw speeds, which result in approximately the same residence time in both single- and twin-screw extruders with and without a mixing element, were determined. Screw speeds of 220 rpm in a single-screw extruder with a mixing element, 180 rpm in a single-screw extruder without a mixing element, and 160 rpm in a twin-screw extruder with and without a mixing element resulted in similar residence times. The presence of a mixing element did not have an effect on vessel dispersion number and flow pattern in the single-screw extruder but it affected vessel dispersion number and changed the flow pattern in the twin-screw extruder. The amount of phosphorus bound to starch did not increase with the mixing element in single- and twin-screw extruders for a constant mean residence time.

Effect of pretreatment and membrane orientation on fluxes for concentration of whey with high foulants by using NH3/CO2 in forward osmosis

Usage of forward osmosis membrane in FO mode, in which active and support layers of the membrane were in contact with the feed and the draw solutions respectively, provided higher initial water flux (12L/m2h) than the usage of membrane in PRO mode (6L/m2h) having opposite orientation but fluxes approached to each other after 4h during concentration of whey with NH3/CO2 as draw salt. High organic and inorganic foulants of whey was considered as reason for observed result in addition to lower solute resistivity. Initial water flux (8,5L/m2h) was lower when pre-treatment was applied before forward osmosis process but final flux (4L/m2h) was equal flux of non pre-treatment. Reduction of solute resistivity or absence of hydraulic pressure can be reasons for lower initial flux. Detection of organic carbon but absence of lactose in draw solution showed passage of molecules being different than lactose into draw solution.

Comparison of polyphenol extractions from olive pomace and solid fraction of olive mill waste water

The solid fraction of olive mill waste water (OMWW) was separated from OMWW and then the solutes in the solid fraction of OMWW were extracted with ethanol. The detection of polyphenols in the ethanol extract showed the presence of polyphenols in the solid fraction of OMWW. Effects of solvent-to-solid ratio, extraction and agitation time on the extraction of polyphenols from the solid fraction of OMWW were examined and the maximum amount of polyphenol was extracted from the solid fraction of OMWW with a solvent-to-solid ratio of 15 at 70 min of extraction and 10 min of agitation time. Percent yields and purities of the polyphenols extracted from solid fraction of OMWW were higher than those of the polyphenols extracted from olive pomace with ethanol at 70 min of extraction and 10 min of agitation time with solvent-to-solid ratio of 15.

Kinetics of Polyphenol Losses and Antioxidant Activity of Extracts from Olive Cake During Evaporation

Polyphenols were extracted from olive cake and then concentrated at 50, 75, and 100°C by the evaporation of extract. Antioxidant activity of total polyphenols in olive cake extract decreased while the concentration of total polyphenols increased during the evaporation of extract at 100°C, but concentration of polyphenols slightly increased while antioxidant activity did not change at 75°C. These results showed that antioxidant activity is not related and estimated with the amount of total polyphenols. Reaction rate for the loss of polyphenols is found zero order at 50 and 75°C with r2 of 0.99 and at 100°C with r2 of 0.85. Low r2 value at 100°C requires the consideration of a different kinetic model to predict the losses of polyhenols at a high temperature of 100°C.