Development of 3D-Printed, Liquisolid and Directly Compressed Glimepiride Tablets, Loaded with Black Seed Oil Self-Nanoemulsifying Drug Delivery System: In Vitro and In Vivo Characterization

Glimepiride is characterized by an inconsistent dissolution and absorption profile due to its limited aqueous solubility. The aim of this study was to develop glimepiride tablets using three different manufacturing techniques, as well as to study their quality attributes and pharmacokinetics behavior. Black seed oil based self-nanoemulsifying drug delivery system (SNEDDS) formulation was developed and characterized. Glimepiride liquisolid and directly compressed tablets were prepared and their pre-compression and post-compression characteristics were evaluated. Semi-solid pastes loaded with SNEDDS were prepared and used to develop three-dimensional printing tablets utilizing the extrusion technique. In vivo comparative pharmacokinetics study was conducted on Male Wistar rats using a single dose one-period parallel design. The developed SNEDDS formulation showed a particle size of 45.607 ± 4.404 nm, and a glimepiride solubility of 25.002 ± 0.273 mg/mL. All the studied tablet formulations showed acceptable pre-compression and post-compression characteristics and a difference in their in vitro drug release behavior. The surface of the liquisolid and directly compressed tablets was smooth and non-porous, while the three-dimensional printing tablets showed a few porous surfaces. The inner structure of the liquisolid tablets showed some cracks and voids between the incorporated tablet ingredients while that of the three-dimensional printing tablets displayed some tortuosity and a gel porous-like structure. Most of the computed pharmacokinetic parameters improved with the liquisolid and three-dimensional printed tablets. The relative bioavailabilities of the three-dimensional printed and liquisolid tablets compared to commercial product were 121.68% and 113.86%, respectively. Therefore, the liquisolid and three-dimensional printed tablets are promising techniques for modifying glimepiride release and improving in vivo performance but more clinical investigations are required.

Impacts of various mixing approaches towards black seed oil-alginate emulsion attributes

Black seed oil (BSO) contains thymoquinone, an active ingredient that is well-known for its antioxidant property. The bitter taste of BSO makes it challenging for the consumers, mainly children and the elderly, to consume it every day. Thus, BSO is encapsulated in alginate beads in micrometre size to enhance its palatability. This encapsulation was previously established in the lab-scale and the standard mixing method to produce a stable BSO-alginate emulsion used a magnetic stirrer coupled with a sonicator. This mixing method is not suitable for the production of BSO beads at a large scale. Hence, this research aims to investigate the impacts of various mixing methods coupled with sonication towards the BSO-alginate emulsion attributes. Four BSOalginate coarse emulsions were prepared using a magnetic stirrer (MS) as the benchmark, overhead stirrer (OS), homogeniser (H), and overhead stirrer combined with homogeniser (OSH). All the coarse emulsions were then sonicated to produce a nanoemulsion using a flow cell sonicator. The coarse emulsions were characterised in terms of dissolution time while the nanoemulsions were characterised in terms of droplet size, polydispersity index, zeta potential, conductivity and absorbance. These characteristics were statistically compared to the benchmark emulsion characteristics. MS, OS, H, and OSH coarse emulsion formation required 45, 230, 102, and 46 minutes to be produced, respectively. There were significant differences (p <0.05) between the droplet size of OSH (266.53±4.36) nm and MS (285.50±1.15) nm emulsions, indicating that the OSH emulsion was more stable. The absorbance of OSH BSO-alginate nanoemulsion was significantly lower (p <0.05) than the benchmark. In comparison to MS as the benchmark, OSH technique produced a stable emulsion in terms of lower dissolution time, droplet size, zeta potential, and absorbance.

Growth performance, hematological parameters and lipid profile of mice treated with black seed oil and vitamin-E

Nigella sativa (Black seed) has been recognized as one of the most popular herbs in many parts of the world for centuries and used as folk medicine to cure different kinds of diseases. Vitamin E is well known for its antioxidative and anti-inflammatory properties, and has been studied in the prevention of cardiovascular disease (CVD). The present study was performed to determine the effect of black seed oil and Vit-E on growth performance and blood biochemistry in mice. A total of 40 mice weight between 25-27 gm were used for conducting the research. At first, the mice were randomly divided into 4 groups consisting 10 mice in each group. Group A served as the control group whereas Group B was administered black seed oil @ 0.5 ml/kg/day, Groups C was taken vitamin E @ 200 mg/kg/day and Group D was received both black seed oil @ 0.5 ml/kg/day + vitamin E @ 200 mg/kg/day respectively for 42 days. Result showed that, body weight of B, C and D group revealed a significant decrease than the control group (p<0.05). Hemoglobin concentration (Hb) and Total Erythrocyte Count (TEC) showed a significant change in B, C and D group than the control group (p<0.05). On the other hand, Total Leukocyte Count (TLC) and Packed Cell Volume (PCV) were insignificant. The results of biochemical test explored that serum cholesterol and triglyceride value decreased significantly whereas HDL increased significantly in black seed oil, Vit-E treated groups than the control group (p<0.05). But the LDL showed no change after treatment. It could be concluded that the black seed oil and Vit-E can be used in the therapeutic strategy of obesity, anemia and coronary diseases. Asian J. Med. Biol. Res. 2021, 7 (2), 132-137

INVESTIGATION OF THE EFFECT OF BLACK SEED OIL ON DIABETES-INDUCED - TESTICULAR DAMAGE: A HISTOPATHOLOGICAL STUDY

In this study, it was aimed to investigate the protective effect of black seed oil against testicular tissue damage in diabetic rats. A total of 18 male rats were divided into 3 groups, including 6 rats in each group.Groups; control (n=6), diabetes (n=6), diabetes + black seed oil (n=6). A single dose of 45 mg / kg streptozocine (STZ) was injected intraperitoneally to induce diabetes. Diabetes + Black seed oil group: For 56 days, 2.5 ml / kg of black seed oil was administered orally to rats.The rats were sacriced at the end of 56 days. Testicular tissues were taken for routine parafn tissue processing for histopathological examination. Parafn sections were stained with Hematoxylin-Eosin and PAS and examined under a light microscope. Atrophy and degeneration were observed in the seminiferous tubules of diabetic group. Histology of black seed oil group sections were similar to that of control group. A signicant difference was found between the black seed oil group and the diabetes group in terms of blood glucose values. As a result, we think that Black Seed Oil ameliorates to the tissue damage caused by diabetes and the decrease in blood sugar value.

In silico identification of compounds from Nigella sativa seed oil as potential inhibitors of SARS-CoV-2 targets

Background The growing number of cases, severity and fatality of the COVID-19 pandemic, coupled with the fact that no cure has been found has made infected individuals especially in Africa, to resort to the consumption of different natural products to alleviate their condition. One of such plant materials that have been consumed to remedy the severity of this viral infection is the oil of Nigella sativa seed commonly called black seed oil. In this study, we extracted and characterized the oil from this seed using gas chromatography coupled to a mass selective detector to identify the component phytochemicals. Site-directed multiligand docking of the identified compounds was performed on SARS-CoV-2 molecular targets- Replicase polyprotein 1a, RNA binding protein of NSP9, ADP ribose phosphatase of NSP3, 3-chymotrypsin-like protease 3CLpro, and RNA-dependent RNA polymerase RDRP, and ACE2–angiotensin-converting enzyme from the Homo sapiens. Results The binding affinity of caryophyllene oxide was the highest on 3CLpro (− 6.0 kcal/mol), NSP3 (− 6.3 kcal/mol), NSP9 (− 6.3 kcal/mol), and RDRP (− 6.9 kcal/mol) targets, while α-bergamotene gave the best binding affinity on RPIA (5.7 kcal/mol) target. The binding affinity of β-bisabolene on the ACE2 target (− 8.0 kcal/mol) was almost the same as Remdesivir (− 8.1 kcal/mol). The ADMET properties of these three phytochemicals showed that they are good drug leads for these SARS-CoV-2 receptors. Conclusion The findings from this study strongly indicate that the reported recovery from COVID-19 infection claimed by patients who consumed black seed oil could be linked to the presence of caryophyllene oxide, α-bergamotene, and β-bisabolene in this natural product.