FORMULATION AND DEVELOPMENT OF FIXED-DOSE COMBINATION OF BI-LAYER TABLETS OF EFAVIRENZ, LAMIVUDINE AND TENOFOVIR DISOPROXIL FUMARATE TABLETS 600 MG/300 MG/300 MG

Objective: This study is to formulate bi-layer tablet as a multidrug regimen against each reference listed drugs of Brand SUSTIVA® (efavirenz tablets 600 mg), EPIVER®(lamivudine tablets 300 mg), and VIREAD®(tenofovir disoproxil tablets 300 mg) to treat human immunodeficiency virus (HIV) infections. Which provides highly active antiretroviral therapy to provide effective treatment. Methods: Bilayer formulation was developed with each blend of layer-I (efavirenz) and layer-II (lamivudine and tenofovir disoproxil fumarate) through wet granulation process and roller compaction process, respectively. Further, both layers were compressed by using bi-layer compression followed by film coating. Layer-I and II formulations were developed by using various concentrations of diluents, surfactants, and disintegrants to improve the solubility of efavirenz and improve the flowability and uniformity of layer-II. Finally, the optimum formulation was developed to compare the in vitro dissolution with each branded formulation. Results: Drug-excipients interaction results revealed that the mixtures of three drug substances in 50 °C/75 % relative humidity (RH) resulted in an increase in tenofovir IMP-E and the highest unknown impurity was significantly increased and additionally decreased tenofovir assay in the presence of efavirenz. Sodium lauryl sulfate is very critical and it acts as a wetting agent and increases the solubility of efavirenz, and directly influences the dissolution of a drug product. Microcrystalline and croscarmellose sodium have a chance to affect the dissolution and friability of tenofovir. Powdered cellulose was acting as a diluent and flow property of the lamivudine part and it also affects the uniformity and dissolution. So, these ranges were optimized. X-ray diffraction (XRD) indicates there are no polymorphic changes for the optimized formulation and there is no interaction between the three active substances, and finally, in vitro dissolution results for the optimized formulation against the reference drugs. Conclusion: Optimum formulation yielded consistent drug release against each branded drug to treat human immunodeficiency virus (HIV1) infections. This formulation is robust and easily scale up for the next stage.

Effect of grated coconut and water ratio and commercial cheese starter percentage on characteristics of soft cheese made from coconut milk

The aim and objective of this research was to produce a soft cheese made from coconut milk and to examine the effect of grated coconut:water ratio (1:1, 1:2 and 1:3) and percentage of commercial cheese starter culture (1% and 1.5%) on its characteristics. The study was conducted using a factorial randomized block design. After two weeks of storage at 4°C, the cheeses (18 samples) were analysed for total lactic acid (LAB) counts, pH, and fat content. The lowest-fat coconut cheese was analysed for proximate and spreading ability. The results showed that the grated coconut:water ratio had a significant effect (P≣0.01) on the total LAB counts, pH value, and fat content of the cheese. The optimum formulation for soft cheese was selected based on the lowest pH (4.64) and fat content (42%) which was reached by using coconut and water 1:1. However, the spreading ability of this cheese could be improved by optimising the growth of starter cultures, water removal and adding stabilizers.

The Potential Use of Cold-Pressed Pumpkin Seed Oil By-Products in a Low-Fat Salad Dressing: The Effect on Rheological, Microstructural, Recoverable Properties, and Emulsion and Oxidative Stability

The cold-pressed pumpkin seed oil by-product (POB) was evaluated for its application as a natural fat substitute and stabilizer in the reduced-fat salad dressings. For this aim, the samples were prepared by combining the xanthan gum (0.2–0.4 g/100 g), POB (1.0–5.0 g/100 g), egg yolk powder (3 g/100 g), and sunflower oil (10–30 g/100 g) in 17 different formulations. The optimization was carried out using response surface methodology (RSM) and full factorial central composite design (CCD). Results showed that all samples presented the shear-thinning (or pseudoplastic) flow behavior with 3.75–16.11 Pa·sn and 0.18–0.30, K and n values, respectively. The flow behavior rheological data were fitted to a power-law model (R2 > 0.99). The samples with high POB and low oil content showed similar K and n values compared to high oil content samples. Additionally, the dynamic rheological properties and three interval thixotropic test (3-ITT) were determined. The G′ value was larger than G″ in all frequency ranges, indicating viscoelastic solid characteristics in all samples. The optimum formulation was determined as 0.384% XG, 10% oil, and 3.04% POB. The samples prepared with the optimum formulation (POBLF-SD) were compared to low-fat (LF-SD), and high-fat (HF-SD) control salad dressing samples based on the rheological properties, emulsion stability, oxidative stability, zeta potential, and particle size. The oxidation kinetic parameters namely, IP, Ea, ΔS++, and ΔG++ showed that the oxidative stability of salad dressing samples could be improved by enriched by POB. The results of the present study demonstrated that POB could be considerably utilized as a natural fat substitute and stabilizer in salad dressing type emulsions.

Streptomycin Sulfate–Loaded Niosomes Enables Increased Antimicrobial and Anti-Biofilm Activities

One of the antibiotics used to treat infections is streptomycin sulfate that inhibits both Gram-negative and -positive bacteria. Nanoparticles are suitable carriers for the direct delivery and release of drug agents to infected locations. Niosomes are one of the new drug delivery systems that have received much attention today due to their excellent biofilm penetration property and controlled release. In this study, niosomes containing streptomycin sulfate were prepared by using the thin layer hydration method and optimized based on the size, polydispersity index (PDI), and encapsulation efficiency (EE%) characteristics. It was found that the Span 60-to-Tween 60 ratio of 1.5 and the surfactant-to-cholesterol ratio of 1.02 led to an optimum formulation with a minimum of size, low PDI, and maximum of EE of 97.8 nm, 0.27, and 86.7%, respectively. The drug release investigation showed that 50.0 ± 1.2% of streptomycin sulfate was released from the niosome in 24 h and reached 66.4 ± 1.3% by the end of 72 h. Two-month stability studies at 25° and 4°C showed more acceptable stability of samples kept at 4°C. Consequently, antimicrobial and anti-biofilm activities of streptomycin sulfate–loaded niosomes against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were found significantly higher than those of free drug, and the minimum inhibitory concentration values decreased 4- to 8-fold. Furthermore, niosome-encapsulated streptomycin up to 1,500 μg/ml exhibited negligible cytotoxicity against the human foreskin fibroblasts cell line, whereas the free drug exhibited slight cytotoxicity at this concentration. Desired physical characteristics and low toxicity of niosomal nano-carriers containing streptomycin sulfate made them a demanded candidate for the treatment of current bacterial infections and biofilms.

The Impact of Improving Dermal Permeation on the Efficacy and Targeting of Liposome Nanoparticles as a Potential Treatment for Breast Cancer

Breast cancer is the most frequent malignancy in women. This work focuses on developing deformable liposomes as a potential carrier for breast cancer treatment and studying the impact of improving dermal permeation on the efficacy and targeting of liposomes. Raloxifene (RXF), an oestrogen antagonist, was used as a model drug. Using Box–Behnken design, different formulations of RXF-loaded deformable liposome (RLDL) were prepared using different propylene glycol, phospholipid and cholesterol concentrations. The percentage of entrapment efficiency (Y1), particle size (Y2), zeta potential (Y3) and steady-state flux (Y4) of the prepared formulations were all evaluated. Y1 and Y4 were significantly increased and Y2 and Y3 were significantly decreased when the propylene glycol concentration was increased. The optimization was obtained and the optimum formulation was that including phospholipid (1.40% w/w), cholesterol (0.15% w/w) and propylene glycol (10% v/v). The selected optimum formulation displayed a % EE of 78.34 ± 1.04% with a steady-state flux of 4.21 ± 0.02 µg/cm2/h. In order to investigate bioavailability, antitumor effectiveness and permeation, the optimum formulation was selected and included in a carbopol gel. The optimum gel formulation had 2.77 times higher bioavailability and, as a result, considerable antitumor action as compared to oral RXF. In conclusion, optimum RLDL gel may be an effective breast cancer treatment.

The Effect of Cold Press Chia Seed Oil By-Products on the Rheological, Microstructural, Thermal, and Sensory Properties of Low-Fat Ice Cream

This study aimed to investigate the utilization of cold-pressed chia-seed oil by-products (CSOB) in a low-fat ice cream formulation as a fat replacer and stabilizer. In the study, ice cream emulsion mixtures were formulated by using 0.2–0.4% xanthan gum (XG), 2.5–12.5% fat, and 1–3% CSOB. Optimization was performed using the response surface methodology (RSM) and full factorial central composite design (CCD) based on the flow behavior rheological properties of the emulsions obtained from 17 different experimental points. All of the emulsion samples showed non-Newtonian shear-thinning flow behavior. The consistency coefficient (Κ) values of the emulsion samples were found to be 4.01–26.05 Pasn and were significantly affected by optimization parameters (p < 0.05). The optimum formulation was determined as 0.29% XG, 2.5% CSOB, 2.5% fat. The low-fat (LF-IC) and full-fat control samples (FF-IC) were compared to samples produced with an optimum formulation (CBLF-IC) based on the steady shear, frequency sweep, and 3-ITT (three interval thixotropy test) rheological properties, thermal properties, emulsion stability, light microscope images, and sensory quality. CBLF-IC showed similar rheological behavior to FF-IC. The mix of CBLF-IC showed higher emulsion stability and lower poly-dispersity index (PDI) value and fat globule diameters than those of FF-IC and LF-IC. The thermal properties of the samples were significantly affected by the addition of CSOB in an ice cream mix. CBLF-IC exhibited a lower temperature range (ΔT), enthalpy of fusion (ΔHf), and freezing point temperature (Tf) than those of FF-IC and LF-IC. While CBLF-IC exhibited a higher overrun value than other samples, it showed similar sensory properties to the FF-IC sample. The results of this study suggested that CSOB could be used successfully in low-fat ice cream production. This study also has the potential to gain new perspectives for the evaluation of CSOB as a fat substitute in a low-fat ice cream.

Preparation, Optimization and Evaluation of Chitosan-Based Avanafil Nanocomplex Utilizing Antioxidants for Enhanced Neuroprotective Effect on PC12 Cells

(1) Introduction: in recent decades, interdisciplinary research on the utilization of natural products as “active moiety carriers” was focused on due to their superior safety profile, biodegradability, biocompatibility and the ability for sustained or controlled release activity. The nano-based neuroprotective strategy is explored as an imperative treatment for diabetic neuropathy (DN). Avanafil (AV), that selectively inhibits the degradation of cGMP-specific phosphodiesterase, thereby increasing the levels of cGMP, makes a decisive mediator for cytoprotection. (2) Methods: AVnanocomplex formulations were prepared by a modified anti-solvent precipitation method and the method was optimized by Box–Behnken design. An optimized formulation was characterized and evaluated for various in vitro parameters; (3) results:based on the desirability approach, the formulation containing 2.176 g of chitosan, 7.984 g of zein and 90% v/v ethanol concentration can fulfill the prerequisites of optimum formulation (OB-AV-NC).OB-AV-NC was characterized and evaluated for various parameters. The neuroprotective mechanism of AV was evaluated by pretreatment of PC12 cells with plain AV, avanafil nanocomplex (NC) without antioxidants (AV-NC) and with antioxidants (α-Lipoic acid LP; Ellagic Acid EA), AV-LP-EA-Nanocomplex has also shown considerable attenuation in intracellular reactive oxygen species (ROS) and lipid peroxidation with a significant increase in the PC 12 viability under HG conditions in comparison to pure AV; (4) conclusion: the nanocomplex of AV prepared to utilize natural polymers and antioxidants aided for high solubility of AV and exhibited desired neuroprotective activity.This can be one of the promisingstrategy to translate the AV nanocomplex with safety and efficacy in treating DN.

Characteristics and Performance of Polysulfone-Polyvinylpyrrolidone Synthetic Hybrid Membrane in Water Purification System

Clean water is a fundamental need for human. Whether it is used for recreational purposes, food production, domestic use and drinking, safe and readily available water is important for everyone. Water scarcity is very serious and is one of the most extensive problems affecting people throughout the world. In this study, the emphasis is to fabricate polysulfone-polyvinylpyrrolidone hybrid membrane with different polymer formulation to study the characteristics and morphology in determining the optimum formulation of polysulfone-polyvinylpyrrolidone hybrid membrane. In this study, polysulfone and polyvinylpyrrolidone were used as the polymers and 1-Methyl-2-Pyrrolidone was used as the solvent. The optimum formulation is obtained by conducting the test on the membrane; permeate flux test, salt rejection test and tensile test. The resulted optimum polysulfone-polyvinylpyrrolidone hybrid membrane were undergone two more tests which were Scanning Electron Microscopy (SEM) and wastewater quality test. These two tests were conducted to measure its ability to filter the wastewater and the pore size of membrane were captured. The optimum Membrane is sample4 which had the highest value of permeate flux with 33.78 L/m2hr, it had removal percentage of 11.76% for salt rejection, decreased 12.42% in conductivity from 3.3 S/m to 2.89 S/m, and it was able to withstand 48 kN/m2 at strain value of 3.6 m/m. The optimum sample 4 has formed a microfiltration membrane with average 3.23 μm pore size which is successfully filter out particles in the wastewater, where it could remove 44.27% turbidity, 23.08% TSS, 14.29% COD, 4.73% TDS, 4.79% conductivity, 4.34% pH and 13.04% colour.