DESIGN, OPTIMIZATION, AND EVALUATION OF RAFT FORMING GASTRO RETENTIVE DRUG DELIVERY SYSTEM OF LAFUTIDINE USINGBOX–BEHNKEN DESIGN

Objective: The current research was aimed to formulate and evaluate raft forming gastro retentive floating drug delivery systems of Lafutidine for improving gastric residence time and sustained drug release for an extended time. Methods: Using Box–Behnken experimental design 17 formulations of lafutidine GRDDS were designed and evaluated for various parameters like physical appearance, pH, In vitro gelling study, in vitro buoyancy study, measurement of viscosity, density measurement, gel strength, drug content, acid neutralization capacity, the profile of neutralization, in vitro dissolution, release kinetic and stability studies. Results: All the evaluations were performed and observed that the values were within range, and the buoyancy lag time ranged within 14.76 to 25.84 sec and the formulations remained buoyant for more than 8h with the gelling time of 12h, the drug content was ranging from 98.96 to 99.55 %, and in vitro release was 86.86 to 99.34% by the end of 12h. The release kinetics followed zero-order with Higuchi’s model that indicating that drug release was found to be followed by the matrix diffusion process. Conclusion: Out of all formulations F3 was the optimized formulation and it was further characterized for FTIR, DSC, and stability studies, which exposed that there were no interactions amongst drug and excipients and no major change in the formulation and found to be stable.

Testing the Fit of Regression Models Estimated with Extremely Small Samples: Application in Pharmaceutical Stability Studies

Pharmaceutical stability studies are conducted to estimate the shelf life, i.e. the period during which the drug product maintains its identity and stability. In the evaluation of process, regression curve is fitted on the data obtained during the study and the shelf life is determined using the fitted curve. The evaluation process suggested by ICH considers only the case of the true relationship between the measured attribute and time being linear. However, no method is suggested for the practitioner to decide if the linear model is appropriate for their dataset. This is a major problem, as a falsely selected model may distort the estimated shelf life to a great extent, resulting in unreliable quality control. The difficulty of model misspecification detection in stability studies is that very few observations are available. The conventional methods applied for model verification might not be appropriate or efficient due to the small sample size. In this paper, this problem is addressed and some developed methods are proposed to detect model misspecification. The methods can be applied for any process where the regression estimation is performed on independent small samples. Besides stability studies, frequently performed construction of single calibration curves for an analytical measurement is another case where the methods may be applied. It is shown that our methods are statistically appropriate and some of them have high efficiency in the detection of model misspecification when applied in simulated situations which resemble pre-approval and post-approval stability studies.

Synthesis, Stability, and Bioavailability of Nicotinamide Riboside Trioleate Chloride

Nicotinamide riboside chloride (NRCl) is an effective form of vitamin B3. However, it cannot be used in ready-to-drink (RTD) beverages or high-water activity foods because of its intrinsic instability in water. To address this issue, we synthesized nicotinamide riboside trioleate chloride (NRTOCl) as a new hydrophobic nicotinamide riboside (NR) derivative. Contrary to NRCl, NRTOCl is soluble in an oil phase. The results of stability studies showed that NRTOCl was much more stable than NRCl both in water and in oil-in-water emulsions at 25 °C and 35 °C. Finally, we evaluated the bioavailability of NRTOCl by studying its digestibility in simulated intestinal fluid. The results demonstrated that NRTOCl was partially digestible and released NR in the presence of porcine pancreatin in a simulated intestinal fluid. This study showed that NRTOCl has the potential to be used as an NR derivative in ready-to-drink (RTD) beverages and other foods and supplement applications.

Analytical Techniques for the Analysis of Lopinavir and Ritonavir in Pharmaceutical Dosage Form and Biological Matrices: A Review

Background: Lopinavir and Ritonavir are the protease inhibitor type of anti-retroviral drugs. Both are used for the treatment of HIV/AIDS. This paper reviews many analytical methods for the analysis of LPV and RTV in pharmaceutical formulations (tablet, capsule, syrup, and bulk) and biological fluids (human plasma, serum, cerebrospinal fluid, rat plasma, and human hair). Objective: The study aims to summarize various ana¬lytical techniques, such as Chromatography, Spectrophotometry; and also hyphenated techniques, such as LC-MS/MS, UPLC-MS for analysis of Lopinavir and Ritonavir. Method: The review deals with com¬prehensive details about the type of various analytical techniques, such as spectroscopy (UV), chromatography (RP-HPLC, HPTLC, UPLC), and hyphenated techniques, i.e., LC-MS/MS, UPLC-MS for the analysis of lopinavir and ritonavir. These techniques are either explored for the quantification, de¬tection of metabolite or for stability studies of the LPV & RTV. Conclusion: The present studies revealed that the HPLC technique along with the spectro-scopic, have been most widely used for the analysis. Out of the developed methods, hyphenated UPLC-MS and LC-MS are very sensitive and helps in the easy estimation of drugs compared to that of the other techniques. This review may provide comprehensive details to the researchers working in the area of analytical research of LPV & RTV.

Ru(III) Complexes with Lonidamine-Modified Ligands

A series of bifunctional Ru(III) complexes with lonidamine-modified ligands (lonidamine is a selective inhibitor of aerobic glycolysis in cancer cells) was described. Redox properties of Ru(III) complexes were characterized by cyclic voltammetry. An easy reduction suggested a perspective for these agents as their whole mechanism of action seems to be based on activation by metal atom reduction. New compounds demonstrated a more pronounced antiproliferative potency than the parental drug; individual new agents were more cytotoxic than cisplatin. Stability studies showed an increase in the stability of complexes along with the linker length. A similar trend was noted for antiproliferative activity, cellular uptake, apoptosis induction, and thioredoxin reductase inhibition. Finally, at concentrations that did not alter water solubility, the selected new complex evoked no acute toxicity in Balb/c mice.

Bio-analytical Approach for Stability Studies of Bendroflumethiazide Materials

In this paper a comprehensive study of stability related, and evidence based best practices of Bio-analytical stability on Bendroflumethiazide drug samples are studied. The proposed approach is very significant and essential for the drugs development process address the specify the acceptancy, purity, efficacy, prediction of strength and quality of the drugs. The stability study constituents several methods like Bench-Top, Auto-sampler, Freeze-Thaw, Dry-extract, Wet-extract, Short-term, long-Term stability studies at relative intervals results the complete stability information about the drug under the proposed and validated method. There ported out comes of this methos shows this drug have good stability according to ICH guidelines.

Setting and Testing of the Out-of-Step Protection at Mongolian Transmission System

Modern distance relays have integrated numerous protection functions, including power-swing blocking and out-of-step or pole-slip tripping functions. The main purpose of the power-swing blocking function is to differentiate faults from power swings and block distance or other relay elements from operating during stable or unstable power swings. Most power-swing blocking elements are based on traditional methods that monitor the positive sequence impedance rate. The required settings for the power-swing blocking elements could be difficult to calculate in many applications, particularly those where fast swings can be expected. For these cases, extensive stability studies are necessary to determine the fastest rate of possible power swings. This paper presents a detailed step-by-step method for settings calculation of out-of-step (OOS) protection, both blocking and tripping functions considering a generic two-source system. Then the method is applied to define the protection relay settings installed at the interconnection between the Russian and Mongolian power systems, as it is crucial to feed the demand-rich Mongolian power system. In this paper, a specific impedance method is used for defining the OOS protection settings. This paper innovates by testing the settings using the recordings of the major events of 15 September 2018 in two approaches: hybrid co-simulation and cyber-physical. Both tests have demonstrated the appropriate performance of the proposed settings and proving the proposed methodology works appropriately.

Design and Development of Mupirocin Nanofibers as Medicated Textiles for Treatment of Wound Infection in Secondary Burns

The present study assessed the topical potential of nanofibers loaded with Mupirocin (MUP) for the treatment of burns. Nanofibers of MUP were composed of Polyvinyl Pyrrolidone (PVP), Gelatin Type-A, and Ethanol using two methods: Solvent casting and Electrospinning. Nanofibers were characterized for Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), Differential scanning calorimetry (DSC), Thermogravimetric analysis (TGA), Drug Content Studies, in-vitro drug permeation, antibacterial and stability studies. The FT-IR studies showed that the Electrospinning technique had a very good mixing of MUP with the polymer. SEM studies showed that the morphology of electrospinning nanofibers had diameters in the range of 70.41 nm- 406.83 nm. The thermal decomposition studies of optimized Nanofiber (E.S.1) were performed by DSC and TGA study and it was found that the formulation had high stability in high-temperature environments. Permeation studies showed that E.S.1 had the highest percentage amount and controlled release of the drug (90 %) up to 8 has compared to other formulations. Nanofibers prepared through the Electrospinning technique showed better antibacterial activity against Staphylococcus aureus as compared to the Solvent casting nanofibers. This research suggested that MUP loaded nanofibers can be potentially used as a topical drug delivery system for the treatment of burns.