Aissms College of Pharmacy

SeDeM analysis enables rapid screening of powders for direct compression (DC) into tablets. Aim of this work was to investigate plain nanosponges (NS) and spray dried nanosponges (SDNS) for direct compressibility using SeDeMExpert system. Beta-cyclodextrin (β-CD) based NS are widely used for solubility, stability enhancement, and taste masking. Evaluation of their compressibility profile will shorten timelines required for early formulation development studies of tablets excipients.

NS were synthesized by crosslinking β-CD with diphenyl carbonate (DPC) and spray dried. They were evaluated for spectral and particle characteristics and characterized by SeDeManalysis. Primary indices of dimension: compressibility, flowability, lubricity, and stability were calculated by converting the micromeritic properties into 'r' values using factors. Radar diagrams were plotted to map micromeritic properties. Avicel^® and Supertab^® were mixed with NS and SDNS to correct deficiencies.

Spectral characterization confirmed formation of NS. SeDeManalysis and radar diagrams conveyed lacunae in powder characteristics. SDNS displayed better micromeritics than NS however compressibility index was deficient in both. Avicel^® and Supertab^® were mixed with NS and SDNS and SeDeM analysis of mixtures revealed superior micromeritic properties providing conclusive proof of direct compressibility. Index of good compressibility (IGC) of mixtures was above limits.

SeDeManalysis is promising technique to characterize powders and predict compressibility of powders. It provides pointers to need for particle engineering to facilitate DC.

The HIV infection in malnourished conditions raises the concerns with antiretroviral medications, which may worsen the already compromised physiological state. The alteration in the plasma protein binding in malnourished HIV patients exacerbates the unbound fraction of antiretroviral medications, resulting in alterations in the therapeutic effectiveness and toxicity. Thus, the present study investigates the effects of protein deficiency and protein-energy malnutrition on the pharmacokinetics of the antiretroviral efavirenz.

Malnutrition was induced in this study through a modified diet containing only 2% protein. The experiment involved 16 Wistar rats, divided into two groups of 8. The control group was provided with a standard pellet diet (AIN 93G) that contained 19% protein, while the second group was subjected to the low-protein (2%) diet for 90 days. Rats were fed ad libitum with their respective diets during this period. On the 90th day, efavirenz (200 mg/kg, p.o.) was administered, and pharmacokinetic parameters were assessed using HPLC analysis.

The findings indicate that the protein-deficient diet successfully created a model of malnutrition, evidenced by a significant reduction in body weight (26%), hemoglobin levels (33%), total protein (27%), and blood albumin (41%) compared to the control group on a standard diet. The pharmacokinetic analysis of efavirenz in the protein-deficient rats revealed an increase in half-life (T_½) by 51.27%, maximum concentration (C_max) by 31.57%, and area under the curve (AUC 0-∞) by 51.40%, alongside a decrease in total body clearance (45.81%) and volume of distribution (12.1%) relative to the pharmacokinetic profile observed in rats on the standard AIN 93G diet.

These findings indicate that the pharmacokinetic profile of efavirenz is significantly altered under protein-deficient conditions. Therefore, it is recommended that further pharmacokinetic studies be conducted in patients with protein deficiency to determine if standard dosing of efavirenz should be adjusted based on the individual's nutritional status.

This study reports the efficient catalysis of a three-component reaction involving 5-(substituted phenyl)-1,3,4-thiadiazol-2-amine, quinoline-2-carbaldehyde, and tri-Et phosphite, using zirconium oxychloride (ZrOCl₂) as a catalyst in ethanol under reflux conditions.The reaction yields α-aminophosphonates in good to excellent yields.Notably, the catalyst can be recovered and reused multiple times without significant loss of activity.A series of di-Et (((5-(substituted phenyl)-1,3,4-thiadiazol-2-yl)amino)(quinolin-2-yl)methyl)phosphonate derivatives was synthesized and evaluated for in vitro anticancer activity against the HCC827 and H1975 human non-small cell lung cancer cell lines using the MTT assay.The structure-activity relationship (SAR) anal. revealed that electron-withdrawing groups on the Ph ring enhance anticancer activity, while electron-donating groups, the presence of an alkyl chain between the thiadiazole and Ph rings, and increased steric bulk on the Ph ring are detrimental to activity.Addnl., due to their low selectivity towards wild-type EGFR (WT-EGFR), the synthesized compounds may exhibit reduced toxicity associated with WT-EGFR inhibition.Compounds 4-nitro and 4-bromo derivatives showed selective cytotoxicity toward cancer cells and did not display toxicity against normal cells at concentrations up to IC₅₀ >20μM.These findings provide valuable leads that merit further optimization for the development of improved cancer therapeutics.