Journal of Applied Pharmaceutical Sciences and Research

TRASTUZUMAB DERUXTECAN: NOVEL ANTIBODY-DRUG CONJUGATE TARGETING HER2 IN PATIENTS WITH GASTRIC ADENOCARCINOMA

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Gastric cancer (GC) is one of the main causes of death from cancer with a multifactorial origin and is characterized by the expression of a gene known as HER2. This gene promotes cell proliferation and prevents apoptosis of cancer cells, facilitating uncontrolled cell growth. Trastuzumab Deruxtecan (T-DXd) is a drug for the treatment of tumors with a heterogeneous expression of HER2 that are resistant to conventional anti-HER2 therapy. It is believed that the positive results obtained from Trastuzumab Deruxtecan in the treatment of
gastric cancer are related to its potent inhibitory effect of topoisomerase I, the stability of the linker in plasma, as well as its bystander effect. Furthermore, the drug is more efficiently delivered to its target (tumor cell), resulting in a higher concentration of the cytotoxic agent at the site of action. Another point to highlight is that trastuzumab deruxtecan has benefits in treating breast cancer compared to other anti-HER2 therapies since more patients using this drug presented positive responses compared to trastuzumab emtansine (TDM1), in addition to presenting longer survival and fewer adverse effects. Thus, this literature review shows that T-DXd is a promising therapy of extreme importance and with great capability to respond to cancers with low expression of HER2 and to HER2-positive cancers that are insensitive to the trastuzumab emtansine drug.

FORMULATION AND EVALUATION OF FAST DISSOLVING TABLET OF LEVOCETIRIZINE DIHYDROCHLORIDE AND MONTELUKAST SODIUM

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Introduction: Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Objective: The aim of the present study was to formulate fast-dissolving tablets of Levocetirizine dihydrochloride (LEV) and Montelukast
sodium (MON) by direct compression method. Material And Methods: An attempt was made to mask the bitter taste of Levocetirizine by preparing an ion exchange resin complex by a batch method using Kyron T-104. The tablets were prepared using mannitol, microcrystalline cellulose as diluents, and croscarmellose sodium and crospovidone as super disintegrants. Parameters like a drug: resin ratio, pH & swelling time were successfully optimized to prepare the drug resin complex. The fast-dissolving tablets were characterized for various pre and post-compression parameters along with disintegration time, content uniformity, wetting time, in-vitro drug release, in vivo taste evaluation, and compatibility studies. Result and Discussion: The tablets prepared by direct compression method possess a hardness of 3.4 to 3.6 Kg/cm², percentage friability of 0.65 to 0.80, in vitro disintegration time of 29.82 to 51.7 seconds, and wetting time of 20.4 to 46.8 seconds. The formulation (F4)
containing crospovidone and croscarmellose sodium in 2:4 ratios showed better disintegration time and more than 99% drug release within 6 minutes. Comparative taste evaluation proves the palatability of formulated tablets. Results of stability studies were also found in acceptable limits. Conclusion: The prepared orodispersible tablets disintegrate within seconds without the need for water and enhance absorption; this
may lead to increased bioavailability of LEV as well as MON.

IN-SILICO DOCKING STUDIES OF CARBONIC ANHYDRASE INHIBITORS IN THE MANAGEMENT OF NEUROPATHIC PAIN

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Background: In the present study, the in-silico docking studies of carbonic anhydrase inhibitors with 4RUX i.e. The crystal Structure of Human carbonic Anhydrase II protein was performed in the management of neuropathic pain. Materials and Methods: The crystal structure of protein PDB ID: 4RUX was downloaded from the RCSB PDB database and the ligand molecules of carbonic anhydrase inhibitors were drawn from Marvin Sketch. Docking studies between ligand and protein to predict binding interactions by using AutoDock 4.2 and the receptor-ligand complex interaction viewed by using Biovia Drug Discovery studio. Result: Carbonic anhydrase inhibitors showed binding energy ranging between -5.41 to -8.63. Ganoderic acid A showed better binding energy -8.63 kcal/mol than the standard Acetazolamide -6.22 kcal/mol. Conclusion: The result clearly indicates that among carbonic anhydrase inhibitors, Ganoderic acid A and Morindone show better hydrogen bonding and binding affinity towards carbonic anhydrase II (PDB ID: 4RUX). Thus, conclude that among carbonic anhydrase inhibitors Ganoderic acid A (obtained from Ganoderma lucidium) and Morindone (both obtained from Morinda citrifolia (NONI)} provide the better pharmacological effect.

PREPARATION OF MICROCRYSTALLINE CELLULOSE FROM DISSOLVING CELLULOSE OBTAINED FROM JUTE FIBERS AND ITS APPLICATION IN THE FORMULATION OF FEXOFENADINE HYDROCHLORIDE TABLET DOSAGE FORM

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Introduction: The most affordable tablet form is microcrystalline cellulose (MCC), a popular pharmaceutical excipient that is utilized as a filler or binder in immediately compressible tablets. Methods: In the present study, we extracted dissolving cellulose from jute fibers by treatment with 0.1 N hydrochloric acid solution and 20% w/w sodium hydroxide solution at high temperature and pressure. The dissolving cellulose was subjected to acid hydrolysis at 100 ⁰C for 2 h with 2 N hydrochloric acid. The identity of the MCC was confirmed by FT-IR and by determining the degree of polymerization. To evaluate the flow property, we determined the bulk, density, tapped density, Hausner index, Carr’s index and angle of repose. The tableting property of the prepared MCC was evaluated by making fexofenadine hydrochloride tablets.

Result and Discussion: The dissolving cellulose contains 94.67% α-cellulose The DP of the MCC was found 191. The powder properties such as bulk density, tapped density, Hausner index and Carr’s index, angle of repose values are comparable with that of standard Avicel PH102. The hardness, friability, disintegration time and % dissolved in 30 minutes were dissolution value of the tablets 5.6 kg, 0.34%, 178.17 sec and 83.89%, respectively. All these values are within the United State Pharmacopoeia range and are comparable with the tablets prepared from Avicel PH102 and marketed fexofenadine tablets.

PREVALENCE AND ASSOCIATED FACTORS OF ANEMIA AMONG UNDER FIVE YEARS OLD CHILDREN WHO ATTENDED SPINGHAR MOMAND CURATIVE AND TEACHING HOSPITAL, JALALABAD CITY

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Introduction: When the amount of hemoglobin in the blood is less than two SD (standard deviation) for a specific age and sex, or when the amount of red cells in the peripheral blood is below the normal level, it is called anemia. Blood deficiency is a common global health problem in children. Materials and Methods: This research has been conducted in a descriptive manner in which 200 patients referred to Spinghar Momand Curative and Teaching Hospital from 2022 to 2023 were the target population. Their blood deficiency was taken into consideration on the basis of age, sex and the severity of the disease. Results: The results showed that the overall incidences of anemia were 108 (54%). The cases were 75 (69.4%) in males and 33 (30.5%) in females. Based on location, the cases of anemia were 99 (91.6%) in Nangarhar Province, 8 (7.4%) in Laghman Province and 1 (0.92%) in children from Kunar Province. Based on the severity of disease and age, 45 (41.6%) children less than five-year-old had mild anemia, 59 (54.6%), had moderate anemia, and 4 (3.7%) had severe anemia. The result of laboratory tests showed that in anemia, mean corpuscular volume (MCV), hemoglobin (HB) and hematocrit test (Hct) have changed significantly, but RDW (Red Cell Distribution Width) has not changed much. Discussion: We can summarize that the cases of anemia in children vary based on age, sex and severity of the disease. Furthermore, the level of MCV, HB and HCT exists below the normal range in the child suffering from anemia, while no significant change is visible in the RDW value.