4 research outputs found
Analysis and simulation of slender curved beams
No full textCurved beams have a wide variety of applications that include switches, clamps, suspensions, crane hooks, frames of industrial presses, chains, tools and other devices. However, the existing formulas of stress and deflection calculations on beams are commonly for straight beams that undergo small linear deflections. They are not applicable to curved beams. The depth of the cross section of a slender curved beam is small compared with its radius of curvature. It usually has large deformation. The load-deflection relationship of a slender curved beam is often nonlinear. It was much more challenging to analyze the deformation of a nonlinear slender curved beam than a linear straight beam. In this thesis, the stress calculation formula was presented for slender curved beams. The nonlinear deformations of slender curved beams were analyzed. The deformations and stresses of slender curved beams were simulated. The results of this thesis provide a useful roadmap for analyzing and designing slender curved beams
Design, Synthesis and Pharmacological Evaluation of Novel Pyrimidine Derivatives as Antihyperlipidemic Agents
No full textHyperlipidemia is a prevalent medical condition characterized by elevated levels of lipids, including cholesterol and triglycerides, in the bloodstream. This condition poses a significant risk factor for cardiovascular diseases due to the accumulation of fatty deposits in arteries. Genetic, lifestyle, and dietary factors contribute to its development. Diagnosis involves measuring lipid levels, and management typically includes lifestyle changes and medications. Pyrimidine derivatives, on the other hand, are essential organic compounds with a six-membered heterocyclic ring structure containing carbon and nitrogen atoms. These derivatives play a vital role in genetics and biochemistry. In DNA and RNA, pyrimidine bases such as cytosine, thymine, and uracil form complementary base pairs with purines, facilitating the storage and transmission of genetic information. They are also involved in metabolic pathways, including de novo pyrimidine biosynthesis and salvage pathways. The importance of pyrimidine derivatives extends beyond genetics. Their structural versatility has led to their use as fundamental scaffolds in pharmaceutical compounds. Several drugs, such as anticancer agents and antiviral medications, are derived from the pyrimidine core structure, demonstrating its significance in medicine and drug development. It highlights the interplay between hyperlipidemia, a condition affecting cardiovascular health, and pyrimidine derivatives, crucial components of genetics and biochemistry. Understanding both aspects contribute to advancing medical knowledge and therapeutic strategies, addressing critical health concerns and enabling pharmaceutical innovation
The transdermal route as an alternative for the delivery of drugs for epilepsy and psychotic disorders
No full textTransdermal drug delivery has gained recognition as a promising non-invasive method of administering drugs with several advantages over the traditional oral drug delivery, including extended therapeutic effects, reduced side effects, avoidance of the hepatic first-pass metabolism and target drug delivery. However, the skin presents a significant barrier to drug absorption, and not many drugs can passively diffuse through the skin in amounts sufficient to produce a therapeutic effect. Different methods are being explored to get through this skin barrier, including use of chemical penetration enhancers and microemulsion drug delivery system to increase the drug transport across the skin. The objective of this research work is to explore the feasibility of developing transdermal drug delivery systems for drugs used in the treatment of psychotic disorder and epilepsy. The microemulsion system provides opportunity to use different chemical penetration enhancer in combination to get synergistic effect which increases the drug transport across the skin. Firstly, we have evaluated feasibility of transdermal delivery of olanzapine (OLZ) as satisfactory alternative drug delivery system for the oral route using various chemical penetration enhancers (CPEs). The aim of this study was to obtain the information about the impact and effects of various CPEs on the drug’s permeability. The effects of different CPEs have been determined on permeation profile of OLZ from formulation through human cadaver skin. A control formulation of OLZ in propylene glycol (PG) was prepared for a comparison study against the formulations containing chemical penetration enhancers. Different five chemical penetration enhancers (Oleic Acid, Cineole, Isopropyl Alcohol, Tween 80 and N-methyl pyrrolidone) in concentration of 5% were individually added to the formulation containing OLZ in PG. The in-vitro permeation study was carried out using Franz diffusion cell. Samples from the recipient chamber were collected at 2h, 4h, 8h, 12h and 24h at room temperature over a period of total 24 h. Based on the results obtained, different CPEs have a significant impact on OLZ permeability compared to that of a control formulation. The OLZ formulation with 5% Oleic Acid (OA) showed highest permeability through human cadaver skin. The cytotoxicity study results support the fact that studied models were non-toxic.
Secondly, we have investigated the effect of various penetration enhancers on the transdermal delivery of oxcarbazepine an anti-epileptic drug. The ex-vivo permeation experiments were conducted by using vertical Franz diffusion cells mounted with human cadaver skin to study the percutaneous absorption of oxcarbazepine. Various penetration enhancers (represent enhancer groups - terpenes, ether alcohol, fatty acid, pyrrolidone) at concentration from 5% to 20% w/w were selected. Formulation containing oxcarbazepine an anti-epileptic drug, propylene glycol as a solvent and penetration enhancer were used for evaluating drug penetration. Oxcarbazepine was shown to permeate through human skin in vitro following the use of different penetration enhancers. The microemulsion system was prepared using the chemical enhancers. The selection of microemulsion components were based on its solubilization capacity and enhanced permeation activity. Microemulsions were prepared using selected penetration enhancers, enhanced oxcarbazepine permeation. Furthermore, microemugel was prepared using thickening agent shows comparable permeation as microemulsion.
Lastly, we have investigated the effect of various penetration enhancers on the transdermal delivery of risperidone for psychotic disorder. The chemical enhancers modify skin lipids in different ways and the mechanism of action is linked to their ability to interact with skin lipids, that increase the drug passage through skin and thus contribute to increased permeability. Microemulsions were prepared using selected penetration enhancers with dual role as penetration enhancer as well as component of microemulsion. Our study showed that the flux and the amount permeated of risperidone were significantly increased with the incorporation of various penetration enhancers in the microemulsion formulation. Microemulsion prepared from oleic acid (15%) as oil, tween 80 (15%) as surfactant and isopropyl alcohol (20%) as co-surfactant shows highest permeation across the human cadaver skin. This novel in vitro research disclosed that an optimized microemulsion formulated using penetration enhancers was able to increase permeation of risperidone by 14-fold compared to the control formulation. Further, the stability study of the final microemulsion shows that the microemulsion was stable at room temperature (25°C) and at accelerated temperature (40°C) conditions with no change in the drug content, visual appearance and globule size conclude stable product.
In conclusion, the study demonstrates that utilizing chemical penetration enhancers and optimized microemulsion formulations are feasible approaches for developing transdermal drug delivery systems for psychotic and epilepsy treatments. These findings contribute to the advancement of alternative drug delivery methods that can potentially enhance treatment outcomes for these diseases.Ph.D.Includes bibliographical reference
Immune Checkpoint Inhibitor in Hepatocellular Carcinoma: Response Rates, Adverse Events, and Predictors of Response
No full textBackground/Objectives: Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. Barcelona Clinic Liver Cancer (BCLC) guidelines recommend antiangiogenic agents with immune checkpoint inhibitors as first-line therapy for advanced HCC. We present our experience of treating HCC patients with Atezolizumab–Bevacizumab, their response rates, adverse events, survival, and response and survival predictors. Methods: This retrospective analysis included HCC patients diagnosed at All India Institute of Medical Sciences, New Delhi, India between July 2021 and April 2024 and receiving at least one dose of Atezolizumab–Bevacizumab. The primary outcome was overall response rate (ORR), comprising complete response (CR) and partial response (PR), as per mRECIST criteria. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and predictors of response and survival. Results: Sixty-three patients were analyzed {mean age: 56.0 + 12.7 years; 82.5% males}. Forty-three (68.2%) patients had BCLC stage C HCC. Thirty-five (55.5%) patients belonged to Child–Pugh class A and 28 (44.5%) belonged to Child–Pugh class B. At 1 year, OS was 39% and PFS was 27%. Among 43 patients with data for radiological response, ORR was 48.8% (CR—9.3% and PR—39.5%) and DCR was 62.7% with stable disease (SD) in 13.9% of patients. PD occurred in 37.2% of patients. AFP response predicted radiological response, while Child–Pugh class and BCLC stage predicted survival. Adverse events were reported in 49.2% of patients. Conclusions: Our study shows slightly lower survival than previous studies with Child–Pugh class being the most important determinant of survival. AFP response predicts radiological response and not survival
