FORMULATION AND EVALUATION OF CETIRIZINE HYDROCHLORIDE pH TRIGGED IN-SITU OCULAR GEL

Objective: In the present research work, the aim was to prepare pH trigged in-situ ocular gel of Cetirizine Hydrochloride (CTZ) to improve its local bioavailability at the eye surface. Methods: CTZ in-situ ocular gel was prepared by the pH-trigged method.In-situ CTZ ocular gel was prepared by a pH-sensitive gelling agent (Carbomer) with a one viscosity builder polymer (HPMC E4M).All formulation was evaluated for appearance, pH, viscosity at different pH, gelling capacity, % drug content, and drug release. Nine formulations were prepared and optimized successfully using 32 factorial designs. Optimization was done by DoE software version Version 13.0.10.064 Results:  All nine formulations of in-situ ocular gel were subjected to evaluation. Out of 9 formulations, F3 had a good gelling capacity with the minimum amount of polymer. The appearance of the optimized formulation was translucent and homogenous. The pH of the F3 formulation is 5.55±0.07, which is good for maintaining formulation in the solution stage. Viscosity at 20 RPM of F3 formulation at pH 5.5 is 837.30±1.00 cps, this range of viscosity has good flow properties. Viscosity at 20 RPM of F3 formulation at pH 7.4 is 6800.74± 1.58cps, this range of viscosity has a good gelling capacity which helps to drug retain at the eye surface. Drug content is 100.16± 0.53%. Drug release at 300 min is 69.22 ± 2.12, it can say that the drug may be retained for more than 300 min at the eye surface which is good for reducing dosing frequency.,. Conclusion: CTZ was successfully formulated in pH triggered in-situ gelling system using Carbomer 974P in combination with HPMC E4M. The prepared in-situ gel is easily converted from solution stage to gel stage at the pH of the eye so we can say that the drug in the in-situ ocular gel is more bioavailable than conventional ophthalmic solution  In-vitro results indicated that the in-situ gel system is a viable alternative to conventional ocular drops by virtue of its ability to sustain drug release

FORMULATION AND EVALUATION OF DISPERSIBLE TABLETS OF FLAVONOID PGAL ISOLATED FROM SARACA ASOCA LEAVES

Objective: The study aimed to design and evaluate a dispersible tablet of flavonoid PGAL isolated from Saraca asoca leaves for antidepressant activity. Methods: The phytoconstituent was isolated from a methanolic extract of Saraca asoca leaves using silica gel column (60-120 mesh) chromatography. The dispersible tablets were prepared by direct compression and then evaluated for various tablet evaluation parameters and antidepressant activity performing Tail Suspension Test (TST), Forced Swim Test (FST), Locomotion Activity, Brain Glutamate Level and Brain Nitrite Level. Results: Hardness of 2.85±0.13 kg/cm2 to 3.25±0.15 kg/cm2 and friability of 0.35% to 0.48% indicate that the prepared tablets were mechanically sound. Test for weight variation was also within tolerance limits, i.e. 2.04% to 4.25% difference in weight of the tablet from the average weight of 10 tablets. The tablets also passed the test for drug content uniformity, 97.35% to 100.35%, i.e. always within the prescribed limits of 95% to 105%. Disintegration time, 2 minutes to 2.75 minutes, and dispersion time, 3.25 minutes to 3.75 minutes, were also exemplary. The antidepressant activity was displayed by the optimized formulation as indicated by a significant decrease (p < 0.05) in immobility time in TST as well as FST; a significant decrease (p < 0.05) in the level of brain tissue glutamate as well as nitrite in PGAL formulation treated mice when compared with negative control, as did by standard drug fluoxetine. Conclusion: The formulation has been optimized based on dispersion time. The formulation with minimum dispersion time, i.e. F1, has been considered an optimized formulation. The prepared optimized formulation was found to comply with all physical parameters and antidepressant activity

Codon Usage Bias for Fatty Acid Genes <i>FAE1</i> and <i>FAD2</i> in Oilseed <i>Brassica</i> Species

Codon usage bias (CUB) phenomenon varies with the species and even within the genes of the same species, where few codons are preferred more frequently than their other synonymous codons. It also categorizes the differences between species. Nucleotide compositional analysis reveals the molecular mechanisms of genes and the evolutionary relationship of a gene in dissimilar plant species. In the present study, three orthologous sequences of each FAE1 (FAE1.1, FAE1.2, and FAE1.3) and FAD2 (FAD2.1, FAD2.2, and FAD2.3) genes, from six Brassica species were accessed using the GenBank database. Further, CUB-related parameters such as nucleotide composition (AT and GC content), relative synonymous codon usage (RSCU), the effective number of codons (ENC), frequency of optimal codons (Fop), relative codon usage bias (RCBS), neutrality plot (GC12 vs. GC3), parity rule-2 [(A3/(A3 + T3) vs. (G3/(G3 + C3)], and correspondence analysis (COA) were analyzed to compare codon bias in U’s triangle Brassica species. The FAE1 genes were AT-biased and FAD2 genes were GC-biased across the studied Brassica species. RSCU values indicated that both the genes had moderate codon usage frequency for selected amino acids. The evolutionary study confirmed that codon usage preference is similar within the species grouped into the same cluster for FAE1; however, B. nigra performed differently for FAD2.2 orthologue. The high ENC value, low Fop, and RSCU value highlighted that FAE1 and FAD2 genes had a low level of gene expression and moderate preference for codon usage across the Brassicas. In addition, neutrality plot, parity rule, and correspondence analysis revealed that natural selection pressure had significantly contributed to CUB for FAE1 genes, whereas mutation and selection pressure occurred for FAD2 genes. This study would help to decode codon optimization, improve the level of expression of exogenous genes, and transgenic engineering to increase fatty acid profiling for the betterment of seed oil in Brassica species

Codon Usage Bias for Fatty Acid Genes FAE1 and FAD2 in Oilseed Brassica Species

Codon usage bias (CUB) phenomenon varies with the species and even within the genes of the same species, where few codons are preferred more frequently than their other synonymous codons. It also categorizes the differences between species. Nucleotide compositional analysis reveals the molecular mechanisms of genes and the evolutionary relationship of a gene in dissimilar plant species. In the present study, three orthologous sequences of each FAE1 (FAE1.1, FAE1.2, and FAE1.3) and FAD2 (FAD2.1, FAD2.2, and FAD2.3) genes, from six Brassica species were accessed using the GenBank database. Further, CUB-related parameters such as nucleotide composition (AT and GC content), relative synonymous codon usage (RSCU), the effective number of codons (ENC), frequency of optimal codons (Fop), relative codon usage bias (RCBS), neutrality plot (GC12 vs. GC3), parity rule-2 [(A3/(A3 + T3) vs. (G3/(G3 + C3)], and correspondence analysis (COA) were analyzed to compare codon bias in U&rsquo;s triangle Brassica species. The FAE1 genes were AT-biased and FAD2 genes were GC-biased across the studied Brassica species. RSCU values indicated that both the genes had moderate codon usage frequency for selected amino acids. The evolutionary study confirmed that codon usage preference is similar within the species grouped into the same cluster for FAE1; however, B. nigra performed differently for FAD2.2 orthologue. The high ENC value, low Fop, and RSCU value highlighted that FAE1 and FAD2 genes had a low level of gene expression and moderate preference for codon usage across the Brassicas. In addition, neutrality plot, parity rule, and correspondence analysis revealed that natural selection pressure had significantly contributed to CUB for FAE1 genes, whereas mutation and selection pressure occurred for FAD2 genes. This study would help to decode codon optimization, improve the level of expression of exogenous genes, and transgenic engineering to increase fatty acid profiling for the betterment of seed oil in Brassica species

Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone: optimization, characterization, pharmacokinetic, and hepatotoxicity studies

Thymoquinone (TQ) is an antioxidant, anti-inflammatory, and hepatoprotective compound obtained from the black seed oil of Nigella sativa. However, high hydrophobicity, instability at higher pH levels, photosensitivity, and low oral bioavailability hinder its delivery to the target tissues. A self-nanoemulsifying drug delivery system (SNEDDS) was fabricated using the microemulsification technique to address these issues. Its physicochemical properties, thermodynamic stability studies, drug release kinetics, in vivo pharmacokinetics, and hepatoprotective activity were evaluated. The droplet size was in the nano-range (< 90 nm). Zeta potential was measured to be -11.35 mV, signifying the high stability of the oil droplets. In vivo pharmacokinetic evaluation showed a fourfold increase in the bioavailability of TQ-SNEDDS over pure TQ. Furthermore, in a PCM-induced animal model, TQ-SNEDDS demonstrated significant (p < 0.05) hepatoprotective activity compared to pure TQ and silymarin. Reduction in liver biomarker enzymes and histopathological examinations of liver sections further supported the results. In this study, SNEDDS was demonstrated to be an improved oral delivery method for TQ, since it potentiates hepatotoxicity and enhances bioavailability