Formulation, optimization and evaluation of ocular gel containing nebivolol Hcl-loaded ultradeformable spanlastics nanovesicles: In vitro and in vivo studies.

The study aims to improve the ocular delivery of Nebivolol HCL (NBV) belonging to the Biopharmaceutics classification system (BCSII) by using spanlastic nanovesicles (SNVs) for ophthalmic delivery and incorporating them into hydroxypropyl methylcellulose gel with ketorolac tromethamine (KET) as an anti-inflammatory to improve glaucoma complications like Conjunctivitis. SNVs were prepared by ethanol injection technique using span (60) as a surfactant and labrasol as an edge activator (EA). The impact of formulation factors on SNVs properties was investigated using a Box-Behnken design. In vitro evaluations showed that the formulations (F1, F4, and F14), containing Span 60 and labrasol as EA (25%, 50%, and 25%), exhibited high EE% with low PS and high ZP and DI. Additionally, 61.72 ± 0.77%, 58.97 ± 1.44%, and 56.20 ± 2.32% of the NBV amount were released from F1, F4, and F14 after 5 h, compared to 93.94 ± 1.21% released from drug suspension. The selected formula (G1), containing F1 in combination with KET and 2% w/w HPMC, exhibited 76.36 ± 0.90% drug release after 12 h. Ex vivo Confocal laser scanning revealed a high penetration of NBV-SNVs gel that ascertained the results of the in-vitro study. In vivo studies showed a significant decrease in glaucoma compared to drug suspension, and histopathological studies showed improvement in glaucomatous eye retinal atrophy. G1 is considered a promising approach to improving ocular permeability, absorption, and anti-inflammatory activity, providing a safer alternative to current regimens.

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies.

Purpose: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. Methods: Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes. Results:  Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration. Conclusion: The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.

Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro, in silico, and in-vivo study.

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (-18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ's antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.

Construction of sublingual trilaminated Eszopiclone fast dissolving film for the treatment of Insomnia: Formulation, characterization and In vivo clinical comparative pharmacokinetic study in healthy human subjects.

BACKGROUND: Disturbed sleep can cause to m health problems such as cognitive impairment, depressed mood, and negative effects on cardiovascular, endocrine, and immune function. This study formulates and optimizes Eszopiclone trilaminate fast dissolving film. METHODS: Prepared Eszopiclone trilaminate fast dissolving film (Eszopiclone TFDF) was characterized by disintegration time, drug release, tensile strength (TS), percentage elongation (EB%), folding endurance, taste masking test, and in vitro dissolution test. The selected formulas were F2 (0.5% xanthan gum, 10% propylene glycol), F4 (3% sodium alginate, 10% propylene glycol) and F6 (1.5% pullulan, 10% propylene glycol) were subjected to in vivo study compared to conventional Lunesta® tablet. RESULTS: The results indicated that disintegration time was in the range of 940 m. Drug release was found to be in the field of 78.51%-99.99%, while TS values and EB% differed from 11.12 to 25.74 (MPa) and 25.38%-36.43%, respectively. The folding endurance went between 200 and 300 times. All formulas exhibited acceptable uniformity content, surface pH, film thickness, and a good taste feeling. CONCLUSION: F4 had the highest Cmax (39.741 ± 6.785-µg/l) and lower Tmax (1.063 hr) among other formulas and conventional tablets. Therefore, FDFs' technology could increase the therapeutic effect of Eszopiclone.