Informatics Publishing Limited

Edula Sravani ¹, M. K. Chaitanya Mannava ², Damandeep Kaur ³, B. R. Annapurna ¹, Ronaq Ali Khan ³, Kuthuru Suresh ³, Sudhir Mittapalli ³, Ashwini Nangia ², B. Dinesh Kumar ¹

Affiliations
1 Centre for Advanced Research for Pre-Clinical Toxicology, Food and Drug Toxicology Research Centre, National Institute of Nutrition (Indian Council of Medical Research), Hyderabad 500 007, IN
2 Crystalin Research Private Limited, Technology Business Incubator, University of Hyderabad Campus, Hyderabad 500 046, IN
3 School of Chemistry, University of Hyderabad, Central University P.O., Prof. C. R. Rao Road, Hyderabad 500 046, IN

Abstract

Temozolomide (TMZ) is a frontline prodrug for the treatment of glioblastoma multiforme (brain cancer) approved by the US-FDA in 1999. A limitation with this otherwise potent and selective DNA alkylating agent is degradation of the prodrug to the inactive product 5-aminoimidazole-4-carboxamide (AIC) by incipient hydrolysis during storage. This transformation not only makes the drug less effective (due to hydrolysis of the active drug), but also causes discoloration from white to pink and tan brown colour (due to AIC contamination), which can make patients anxious and suspicious about the drug efficacy. We solved the stability issue of TMZ by preparing its succinic acid (SA) cocrystal and showed that TMZ-SA is stable for over 6 months in accelerated stability conditions of 40°C, 75% RH, as confirmed by PXRD. TMZ-SA retained its white colour for over 6 months compared to the tan-brown discoloration for TMZ in less than 1 month. Based on the enhanced stability and comparable dissolution profile of TMZ-SA, we now take forward TMZ-SA pharmaceutical cocrystal to stability assessment by HPLC analysis and preclinical bioavailability and bioequivalence with the reference drug. We observed that there were no significant differences in the pharmacokinetic profile of the test cocrystal TMZ-SA compared to standard drug TMZ in Sprague Dawley rats. The bioavailability ratio was found to be in the range 102-109%. Pharmacokinetic parameters such as T_max, C_max, T_1/2, AUC and Ke are slightly superior for TMZ-SA and the toxico-kinetic profile is also better than TMZ. Most significantly, it has been shown that the active drug is released from the hydrogen-bonded cocrystal and was detected in the brain tissue of rats. Thus we report on a pharmaceutical cocrystal complying with the United States Food and Drug Administration guidance on pharmaceutical cocrystals. These results suggest that TMZSA cocrystal with improved physico-chemical properties is bioequivalent and has superior stability compared to the reference drug TMZ and a potential lead for an improved TMZ formulation.

Keywords

Bioavailability, Bioequivalence, Cocrystal, Glioma, Toxico-Kinetic Profile.

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N. Kishore Nath ¹, B. Dinesh Kumar ¹

Affiliations
1 Advanced Systems Laboratory, Kanchanbagh, Hyderabad, IN

Abstract

Vectoring tests are carried out on each flex nozzle system of a rocket motor to verify the performance of flex seal using Electro Mechanical actuators, mirror image sensors and electronic controller. These tests are done for acceptance of the flex nozzle control system in the missile. The flex nozzle controls are tested for sine, ramp, frequency, response commands. During the tests the Command, Pitch, Average, Main Voltages are recorded using DAC. The flex nozzle system is integrated to the pressure chamber in horizontal condition and the Electro Mechanical actuators and mirror image sensors are assembled to the flex nozzle systems. The Electro Mechanical actuators are connected to the battery or 70V power supply to operate the actuators. Then the vectoring tests are performed using the Electro Mechanical actuators. LVDT'S are mounted on nozzle for displacement measurement. The chamber is pressurized pneumatically up to 2 bar.

Keywords

Flex Nozzle System, Electro Mechanical Actuators, Vectoring Tests, Digital Controllers.

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Satya Narayana Gupta ¹, N. Mahesh ¹, B. Dinesh Kumar ¹

Affiliations
1 Aerospace Engineering, MLR Institute of Technology, Hyderabad, IN

Abstract

The overall objective of this project was to evaluate and compare the fatigue performance of two competing manufacturing technologies for aerospace crankshafts, namely forged steel and ductile cast iron. In this project a dynamic simulation was conducted on two crankshafts, forged steel and ductile cast iron, from similar four cylinder four stroke engines. Finite element analysis was performed to obtain the variation of stress magnitude at critical locations. The pressure-volume diagram was used to calculate the load boundary condition in dynamic simulation model, and other simulation inputs were taken from the engine specification chart. The dynamic analysis was done analytically and was verified by simulations in ANSYS. Results achieved from aforementioned analysis were used in optimization of the forged steel crankshaft. Geometry, material, and manufacturing processes were optimized considering different constraints, manufacturing feasibility, and cost. The optimization Process included geometry changes compatible with the current engine, fillet rolling, and the use of micro alloyed steel, resulting in increased fatigue strength and reduced cost of the crankshaft, without changing connecting rod and or engine block.

Keywords

Fatigue, Materials, Crankshaft, Ansys, Manufacturing.

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