Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD) with immediate release and improved bioavailability was prepared using Soluplus (Sol) as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal) fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In thein vivostudy, the AUC_(0–72)andCmaxof PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC_(0–72)andCmaxhigher than those with the commercial capsule (Noxafil). Molecular dynamic (MD) simulation studies were carried out usingin silicomolecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

Anterior uveitis is one of the most prevalent forms of ocular inflammation caused by infections, trauma, and other idiopathic conditions if not treated properly, it can cause complete blindness. Therefore, this study aimed to formulate and evaluate dexamethasone sodium phosphate (DSP) loaded polyelectrolyte complex (PEC) nanoparticles (NPs) for the treatment of anterior uveitis. DSP-loaded PEC-NPs were formed through complex coacervation by mixing low molecular weight chitosan and the anionic polymer carboxy methyl cellulose (CMC). The formulations were optimized using Box–Behnken design and evaluated the effect of independent variables: Chitosan concentration, CMC concentration, and pH of chitosan solution on the dependent variables: particle size (PS), Polydispersity Index (PDI), pH of the formulation, and % entrapment efficacy (%EE). The PS, PDI, zeta potential, and pH of the optimized formulation were found 451 ± 82.0995 nm, 0.3807 ± 0.1862, +20.33 ± 1.04 mV and 6.8367 ± 0.0737 respectively. The %EE and drug loading of formulation were 61.66 ± 4.2914% and 21.442 ± 1.814% respectively. In vitro drug release studies of optimized formulation showed the prolonged release up to 12 h whereas, the marketed formulation showed the burst release 85.625 ± 4.3062% in 1 h and 98.1462 ± 3.0921% at 6 h, respectively. Fourier transform infrared studies suggested the effective incorporation of the drug into the PEC-NPs formulation whereas differential scanning calorimetry and x-ray diffraction studies showed the amorphized nature of the drug in the formulation. Transmission electron microscopy study showed self-assembled, nearly spherical, core–shell nanostructures. The corneal permeation study showed higher permeation of the drug from PEC-NPs compared to the marketed formulation. Hen’s Eggs test-Chorioallantoic Membrane test of the optimized formulation revealed non-irritant and safe for ocular administration. Therefore, DSP-loaded PEC-NPs are an effective substitute for conventional eye drops due to their ability to increase bioavailability through longer precorneal retention duration and sustained drug release.

Innovative drug delivery systems based on iron oxide nanoparticles (INPs) has generated a lot of interest worldwide and have prime biomedical benefits in anticancer therapy. There are still issues reported regarding the stability, absorption, and toxicity of iron oxide nanoparticles (INPs) when administered due to its rapid surface oxidation and agglomeration with blood proteins. To solve this problem, we have synthesized trehalose-coated stabilized iron oxide nanoparticles (TINPs) by a co-precipitation technique. The surface coating of INPs with trehalose helps to improve the stability, prevents protein binding, and increase absorption uptake inside the body. Developed TINPs was then loaded with anticancer drug cytarabine by chemical crosslinking encapsulation method using suitable solvent. Engineered cytarabine-loaded trehalose-coated stabilized iron oxide nanoparticles (CY-TINPs) were optimized for particle size, zeta potential (−13.03 mV), and solid-state characterization such as differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and transmission electron microscope (TEM) studies. The particle size of 50 nm was achieved for developed CY-TINPs. The developed CY-TINPs was further evaluated for in vitro cell line investigations which confirmed potential cytotoxic activity. Developed CY-TINPs show remarkable enhancement in in vivo pharmacokinetic parameters C_max as 425.26 ± 2.11 and AUC_0–72 as 11,546.64 ± 139.82 as compared to pure drug. Compared to traditional drug delivery, the CY-TINPs formulation can effectively delay release, improve bioavailability, and boost cytotoxic activity against tumors.

Tenofovir (TNF) is a common component of many antiretroviral therapy regimens, but it is associated with poor membrane permeability and low oral bioavailability. To improve its oral bioavailability and membrane permeability, a self-emulsifying drug delivery system (SEDDS) was developed and characterized, and its relative bioavailability was compared to the marketed tablets (Tenof). Based on solubility and ternary phase diagram analysis, eucalyptus oil was selected as an oil phase, Kolliphor EL, and Kollisolv MCT 70 were chosen as surfactant and cosurfactant, respectively, while glycerol was used as cosolvent in surfactant mixture. Optimized SEDDS formulation F6 showed an oil droplet size of 98.82 nm and zeta potential of -13.03 mV, indicating the high stability of oil droplets. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy characterization studies were also carried out to assess the amorphous and morphological states of the drug in the prepared SEDDS formulation. The in vitro dissolution profile of SEDDS shows the rapid release of the drug. SEDDS F6 demonstrates a higher drug permeability than the plain TNF and TNF-marketed tablets (Tenof). A pharmacokinetic study in rats revealed that SEDDS F6 showed significantly higher C_max and AUC_0-t than the marketed tablets and pure drug suspension. In addition, the relative bioavailability of SEDDS formulation dramatically improved by 21.53-fold compared to marketed tablets and 66.27-fold compared to pure drugs. These findings show that SEDDS composed of eucalyptus oil, glycerol, Kolliphor EL, and Kollisolv MCT 70 could be a useful tool for enhancing physiochemical properties and oral TNF absorption. Therefore, SEDDS has shown promise in improving the oral bioavailability of poorly water-soluble drugs.

Introduction: This study aims to develop co-amorphous Solid Dispersion (SD) system containing antimalarials Artesunate (ARS) and Amodiaquine (AMQ) to improve its oral bioavailability employing the Hot Melt Extrusion (HME) technique. Soluplus® was selected as a polymeric excipient, whereas Lutrol F127, Lutrol F68, TPGS, and PEG400 as surfactants were incorporated along with Soluplus® to enhance extrudability, improve hydrophilicity, and improve the blend viscosity during HME. Soluplus® with surfactant combination successfully stabilizes both drugs during extrusion by generating SD because of its lower glass transition temperature (Tg) and viscoelastic behavior. Methods: Physicochemical characterizations were performed using FTIR, DSC, TGA, and XRD, which confirmed the amorphousization of drugs in the SD system. The molecular level morphology of the optimized formulation was quantified using high-resolution techniques such as Atomic-Force Microscopy (AFM), Raman spectral, and mapping analysis. The transition of the crystalline drugs into a stable amorphous form has been demonstrated by 1H-NMR and 2D-NMR studies. The in vivo pharmacokinetics study in rats showed that the SD-containing drug-Soluplus-TPGS (FDC10) formulation has 36.63-56.13 (ARS-AMQ) folds increase in the Cmax and 41.87-54.34 (ARS-AMQ) folds increase AUC (0–72) as compared to pure drugs. Results: Pharmacokinetic analysis shows that a fixed-dose combination of 50:135 mg of both APIs (ARSAMQ) significantly increased oral bioavailability by elevating Cmax and AUC, in comparison to pure APIs and also better than the marketed product Coarsucam®. . Conclusion: Therefore, the developed melt extruded co-amorphous formulation has enhanced bioavailability and has more effectiveness than the marketed product Coarsucam®.