Alzheimer's disease (AD) is a neurodegenerative disease that affects a wide range of populations and is the primary cause of death in various countries. The treatment of AD is still restricted to oral conventional medicines that act only superficially. Fabrication of intranasal solid lipid nanoparticulate system for the uptake of therapeutic agents will act as a convincing approach with limited off-site toxicity and increased pharmacological activity. The objective of this study was to formulate, optimize, and evaluate the efficiency of rivastigmine tartrate (RT)-loaded intranasal solid lipid nanoparticles (SLNs) employing the solvent-evaporation diffusion method. To optimize the formulation parameters, the central composite design (CCD) was used. Lipid concentration (X1) and surfactant concentration (X2) were considered to be independent variables, while particle size (Y1), percentage entrapment efficiency (Y2), and percentage drug release (Y3) were considered as responses. The solid lipid was glyceryl monostearate, while the surfactant was polysorbate 80. The optimized formulation has a particle size of 110.2 nm, % entrapment efficiency of 82.56%, and % drug release of 94.86%. The incompatibility of drug excipients was established by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Nasal histopathology tests on sheep mucosa revealed that the developed SLNs were safe to utilize for intranasal delivery with no toxicity. Ex vivo permeation investigations revealed that the flux and diffusion coefficients for RT solid lipid nanoparticles and RT solution were 3.378 g/cm2 /h and 0.310–3 cm2 /h, respectively. Stability studies demonstrated that the developed SLNs were stable when stored under various storage conditions. The viability and vitality of adopting a lipid particle delivery system for improved bioavailability via the intranasal route were also established in the in vivo pharmacokinetic investigations. According to the histopathological and pharmacokinetic investigations, the developed formulations were safe, non-lethal, efficient, and robust. These results suggest the potentiality provided by rivastigmine tartrate-loaded solid lipid nanoparticles for nasal delivery.

In the armamentarium of calcium channel blockers appropriately functionalized 3,4-dihydropyrimidin-2(1H)-ones have received considerable attention in recent past owing to their structural similarity with 1,4-dihydropyridine based drugs. In this review, we highlight detailed investigations in the calcium channel blocking and other activities of this category of compounds as well as trace their genesis from 1,4-dihydropyridine based drugs.

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Introduction: Solid Lipid nanoparticles (SLN) are comprising of a solid lipid core with a mean diameter between 50 and 1000 nm. SLN is an advanced carrier system to traditional colloidal carriers such as emulsion, liposomes, and polymeric microparticles. Objective: The objective of this study was to formulate SLN of Itraconazole (ITZ) for intranasal administration. Methods: ITZ –loaded SLN were prepared by high pressure homogenization technique using central composite design (CCD). The concentration of surfactant (X1) and drug to lipid ratio (X2) were considered as independent variables whereas particle size (Y1) and percent entrapment efficiency (Y2) were considered as response. The compatibility of ingredients with drug was tested using differential scanning calorimetry. SLN were characterized for their particle size, entrapment efficiency, transmission electron microscopy, in-vitro drug release, and ex vivo study. Results: The solid lipid nanoparticles were successfully prepared using high pressure homogenization technique and glyceryl monostrearate was used as solid lipid. The lipid ratio significantly increases the particle size as well as entrapment efficiency. The particle size and (%) entrapment efficiency of optimized formulation were found to be 29 nm and 78.9% respectively. The differential scanning calorimetry confirmed that the drug existed in amorphous form. Nasal histopathology study on sheep mucosa revealed that the developed SLN were non-toxic and safe to use for intra-nasal administration. The results of ex vivo study showed that the Higuchi pattern of drug release was followed. The in-vitro release studies showed the significant difference of drug release from ITZ-loaded SLN compared to plain ITZ-solution. Conclusion: ITZ-loaded SLN were successfully prepared and validated. The best batch was selected based on the desired particle size, and EE which are an important characteristic for SLN formulations. The developed formulations were nontoxic as determined by histo-pathological studies.