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In transdermal applications of nonsteroidal anti-inflammatory drugs, the rheological and mechanical properties of the dosage form affect the performance of the drug. The aim of this study to develop emulgel and nanostructured lipid carrier NLC-based gel formulations containing ibuprofen, evaluate their mechanical properties, bioadhesive value and ex-vivo rabbit skin permeability. All formulations showed non-Newtonian pseudoplastic behavior and their viscosity values are suitable for topical application. The particle size of the nanostructured lipid carrier system was found to be 468 ± 21 nm, and the encapsulation efficiency was 95.58 ± 0.41%. According to the index of viscosity, consistency, firmness, and cohesiveness values obtained as a result of the back extrusion study, E2 formulation was found to be more suitable for transdermal application. The firmness and work of shear values of the E2 formulation, which has the highest viscosity value, were also found to be the highest and it was chosen as the most suitable formulation in terms of the spreadability test. The work of bioadhesion values of NLC-based gel and IBU-loaded NLC-based gel were found as 0.226 ± 0.028 and 0.181 ± 0.006 mJ/cm2 respectively. The percentages of IBU that penetrated through rabbit skin from the Ibuactive-Cream and the E2 were 87.4 ± 2.11% and 93.4 ± 2.72% after 24 h, respectively. When the penetration of ibuprofen through the skin was evaluated, it was found that the E2 formulation increased penetration due to its lipid and nanoparticle structure. As a result of these findings, it can be said that the NLC-based gel formulation will increase the therapeutic efficacy and will be a good alternative transdermal formulation. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to use the quality by design (QbD) approach to design a directly compressed fixed-dose combination (FDC) tablet comprising amlodipine besylate and enalapril maleate with biowaiver potential in alignment with the Biopharmaceutical Classification System (BCS). Methods: As a result of the risk assessment, the amounts of the formulation components such as disintegrant, binder, and lubricant were selected as critical material attributes, and the processes of blending and lubrication were accepted as critical process parameters in a screening design of Plackett–Burman. These factors were evaluated based on the statistical significance of their impact on the drug product's content uniformity, assay, friability, disintegration, and dissolution. The most significant factors determined with the use of Pareto charts and half-normal graphs were the amount of lubricant and disintegrant and blending time, all of which were subsequently optimized using Box-Behnken Design. The optimum formulation was evaluated with in vitro quality tests and in vivo blood pressure–lowering efficacy tests, the results of which were compared to the individual references in rats. Results: As a result of the optimization process, a design space was established for the critical factors. FDC product showed quality and dissolution profiles similar to those of the references. Combination therapy was superior to individual drugs in rats (p < 0.05). Conclusion: It was concluded that an FDC product eligible for BCS-based biowaiver can be developed systematically by using the QbD concept. It was demonstrated that using scanning designs prior to optimization can reduce the number of unnecessary experiments and yield more reliable results in less time. [ABSTRACT FROM AUTHOR]