UNASSIGNED: The study aimed to systematically enhance the fabrication process of flurbiprofen-loaded bilosomes (FSB) using Quality by Design (QbD) principles and Design of Experiments (DOE). The objective was to develop an optimized formulation with improved entrapment efficiency and targeted drug delivery capabilities.
UNASSIGNED: The optimization process involved applying QbD principles and DOE to achieve the desired formulation characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) were incorporated to impart magnetic responsiveness. The size, entrapment efficiency, morphology, and in vitro release patterns of the FSB formulation were evaluated. Additionally, an in situ forming hydrogel incorporating FSB was developed, with its gelation time and drug release kinetics assessed. In vivo studies were conducted on osteoarthritic rats to evaluate the efficacy of the FSB-loaded hydrogel.
UNASSIGNED: The optimized FSB formulation yielded particles with a size of 453.60 nm and an entrapment efficiency of 91.57%. The incorporation of SPIONs enhanced magnetic responsiveness. Morphological evaluations and in vitro release studies confirmed the structural integrity and sustained release characteristics of the FSB formulation. The in situ forming hydrogel exhibited a rapid gelation time of approximately 40 ± 1.8 s and controlled drug release kinetics. In vivo studies demonstrated a 27.83% reduction in joint inflammation and an 85% improvement in locomotor activity in osteoarthritic rats treated with FSB-loaded hydrogel.
UNASSIGNED: This comprehensive investigation highlights the potential of FSB as a promising targeted drug delivery system for the effective management of osteoarthritis. The use of QbD and DOE in the formulation process, along with the integration of SPIONs, resulted in an optimized FSB formulation with enhanced entrapment efficiency and targeted delivery capabilities. The in situ forming hydrogel further supported the formulation\'s applicability for injectable applications, providing rapid gelation and sustained drug release. The in vivo results corroborate the formulation\'s efficacy, underscoring its potential for improving the treatment of osteoarthritis.

This study validates a stability-indicating LC method for detecting organic impurities in the chlorzoxazone dosage form. Using a Waters X-Select R HSS T3 analytical column, mobile phase of it was made by mixing of water, methanol, and glacial acetic acid in the ratio of 700:300:10 (v/v/v). The drug product and drug substance were subjected to the stress conditions such as acid, base, oxidation, heat, and photolysis as per the recommendations of the International Conference on Harmonization (Q2) methodology. The study revealed the susceptibility of 4-chloro-2-aminophenol to alkaline environments, emphasizing peak homogeneity and stability. The method verification, per ICH guidelines and USP<1225>, established precision, specificity, linearity, accuracy, and robustness for quality control. The mean impurity recovery ranged from 95.5% to 105.2%, the correlation coefficient (r) was greater than 1.000, and the RSD values (n = 6) ranged from 0.6% to 5.1% across the LOQ-150% ranges. Full-factorial design tested final method conditions, evaluating multiple parameters concurrently. Graphical optimization within the design space defined strong method requirements, ensuring consistent and reliable outcomes. The study develops and validates chlorzoxazone stability-indicating methods, employing advanced statistical approaches like design of experiments and factorial design, with resilient conditions established through graphical optimization of the design space.

The present study describes a set of methodological procedures (seldom applied together), including (i) development of an alternative adsorbent derived from abundant low-cost plant biomass; (ii) use of simple low-cost biomass modification techniques based on physical processing and chemical activation; (iii) design of experiments (DoE) applied to optimize the removal of a pharmaceutical contaminant from water; (iv) at environmentally relevant concentrations, (v) that due to initial low concentrations required determination by ultra-performance liquid phase chromatography coupled to mass spectrometry (UPLC-MS/MS). A central composite rotational design (CCRD) was employed to investigate the performance of vegetable sponge biomass (Luffa cylindrica), physically processed (crushing and sieving) and chemically activated with phosphoric acid, in the adsorption of the antibiotic trimethoprim (TMP) from water. The optimized model identified pH as the most significant variable, with maximum drug removal (91.1 ± 5.7%) achieved at pH 7.5, a temperature of 22.5 °C, and an adsorbent/adsorbate ratio of 18.6 mg µg-1. The adsorption mechanisms and surface properties of the adsorbent were examined through characterization techniques such as scanning electron microscopy (SEM), point of zero charge (pHpzc) measurement, thermogravimetric analysis (TGA), specific surface area, and Fourier-transform infrared spectroscopy (FTIR). The best kinetic fit was obtained by the Avrami fractional-order model. The hypothesis of a hybrid behavior of the adsorbent was suggested by the equilibrium results presented by the Langmuir and Freundlich models and reinforced by the Redlich-Peterson model, which achieved the best fit (R2 = 0.982). The thermodynamic study indicated an exothermic, spontaneous, and favorable process. The maximum adsorption capacity of the material was 2.32 × 102 µg g-1 at an equilibrium time of 120 min. Finally, a sustainable and promising adsorbent for the polishing of aqueous matrices contaminated by contaminants of emerging concern (CECs) at environmentally relevant concentrations is available for future investigations.

In recent years, the field of analytical chemistry has witnessed a notable shift towards the adoption of greener chromatographic methods, aiming to minimize the environmental impact. An effective strategy involves substituting conventional harmful organic solvents with environmentally friendly alternatives, reducing the use of hazardous chemicals that contribute to environmental concerns. However, separating drug substances without the use of buffers and organic solvents presence is a big challenge. To overcome this challenge, a combination of quality-by-design (QbD) and green analytical chemistry (GAC) was employed in this study for method development. A high-performance liquid chromatography (HPLC) method was successfully developed and validated for the simultaneous determination of Nebivolol hydrochloride, Telmisartan, Valsartan, and Amlodipine besylate. The method utilized a mobile phase composed of a mixture of 0.1 % formic acid in water (pH: 2.5) and ethanol. A regular octadecyl silica (ODS) column was employed, and UV detection at 220 nm was utilized. The method exhibited linearity within the concentration range of 25-75 μg/mL for Telmisartan and 150-450 μg/mL for Nebivolol Hydrochloride, Valsartan, and Amlodipine besylate and the correlation coefficient was greater than 0.999 for all the analytes. Limits of detection (LOD) and quantification (LOQ) were determined as 0.01 and 0.04 μg/mL for Telmisartan, 0.06 and 0.20 μg/mL for Nebivolol Hydrochloride, 0.08 and 0.25 μg/mL for Amlodipine besylate, and 0.14 and 0.46 μg/mL for Valsartan, respectively. The developed method underwent thorough validation, encompassing various parameters such as linearity, accuracy, precision, LOD, LOQ, robustness, and ruggedness. The mean recovery values were observed to range between 98.86 % and 99.89 %. The accuracy demonstrated was consistently above 98.98 % for both intra-day and inter-day precisions were with the relative standard deviations less than 2 %. To establish its robustness, a quality-by-design-based experimental design (DoE) approach was implemented. Additionally, the method\'s environmental friendliness was evaluated using the Analytical Greenness metric (AGREE) an analytical eco scale, both confirming its alignment with sustainable practices and reduced ecological impact. The sustainability of the solvent used in the current study was evaluated by Green Solvents Selecting Tool (GSST) Further, the developed method greenness was evaluated with the green analytical tools such as Analytical method greenness score (AMGS) and using the recently released White Analytical Chemistry (WAC) using RGB assessment tool. By employing this greener approach to chromatography method, this study contributes to the ongoing efforts in analytical chemistry to promote sustainable practices and minimize the environmental footprint of analytical methods.

Twin-screw wet granulation (TSG) is a continuous manufacturing technique either for granules as final dosage form or as an intermediate before tableting or capsule filling. A comprehensive process understanding is required to implement TSG, considering various parameters influencing granule and tablet quality. This study investigates the impact of screw configuration on granule properties followed by tableting, using a systematic approach for lactose-microcrystalline cellulose (lactose-MCC) and ibuprofen-mannitol (IBU) formulations. The most affecting factor, as observed by other researchers, was the L/S ratio impacting the granule size, strength and tabletability. Introducing tooth-mixing-elements at the end of the screw, as for the IBU formulation, resulted in a high proportion of oversized granules, with values between 36% and 78%. Increasing the thickness of kneading elements (KEs) produced denser, less friable granules with reduced tablet tensile strength. Granulation with more KEs, larger thickness or stagger angle increased torque values and residence time from 30 to 65 s. Generally, IBU granules exhibited high tabletability, requiring low compression pressure for sufficient tensile strength. At a compression pressure of 50 MPa, IBU tablets where at least one kneading zone was included resulted in approximately 2.5 MPa compared to lactose-MCC with 0.5 MPa. In conclusion, the TSG process demonstrated robustness by varying the screw design with minimal impact on subsequent tableting processes.

Nanoparticle-mediated mRNA delivery has emerged as a promising therapeutic modality, but its growth is still limited by the discovery and optimization of effective and well-tolerated delivery strategies. Lipid nanoparticles containing charged or ionizable lipids are an emerging standard for in vivo mRNA delivery, so creating facile, tunable strategies to synthesize these key lipid-like molecules is essential to advance the field. Here, we generate a library of N-substituted glycine oligomers, peptoids, and undertake a multistage down-selection process to identify lead candidate peptoids as the ionizable component in our Nutshell nanoparticle platform. First, we identify a promising peptoid structural motif by clustering a library of >200 molecules based on predicted physical properties and evaluate members of each cluster for reporter gene expression in vivo. Then, the lead peptoid motif is optimized using design of experiments methodology to explore variations on the charged and lipophilic portions of the peptoid, facilitating the discovery of trends between structural elements and nanoparticle properties. We further demonstrate that peptoid-based Nutshells leads to expression of therapeutically relevant levels of an anti-respiratory syncytial virus antibody in mice with minimal tolerability concerns or induced immune responses compared to benchmark ionizable lipid, DLin-MC3-DMA. Through this work, we present peptoid-based nanoparticles as a tunable delivery platform that can be optimized toward a range of therapeutic programs.

Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) is a common analytical procedure used to quantitate critical quality attributes relating to the purity and glycosylation of monoclonal antibodies (mAbs). In this study, the application of an Analytical Quality by Design framework incorporating Design of Experiments was used to develop and validate both non-reduced (CE-NR) and reduced (CE-R) versions of this analytical procedure. Formal risk assessments were used to identify critical method attributes for optimization based on their potential impacts to performance criteria outlined in an analytical target profile. The resulting response surfaces connecting these critical factors to method performance were then utilized to generate a harmonized procedure to reduce execution risk across CE-R and CE-NR applications. Validation of these procedures according to regulatory guidelines support that they meet their required performance criteria, and a multivariate assessment of procedure robustness indicates that method parameters are in a sufficient state of control to ensure appropriate quantitation of mAb quality. Overall, this study demonstrates the utility of adopting an Analytical Quality by Design framework to leverage multidimensional knowledge from multiple critical method parameters to ensure an analytical procedure is fit-for-purpose.

UNASSIGNED: This work aims to present a Quality-by-Design (QbD) step-by-step methodology to formulate anti-ulcer and gastro-protective oral suspensions.
UNASSIGNED: Sucralfate was used as a drug model. The Quality Target Product Profile was established early during preformulation. Viscosity, resuspendability, pH, and density were assessed through the screening of several suspension platforms based on different prototype compositions. A compatibility study between the active pharmaceutical ingredient and the excipients was performed by thermal analysis and infrared spectroscopy. An Ishikawa fishbone diagram and Failure Mode and Effect Analysis were employed to identify the Critical Material Attributes (CMAs), Critical Process Parameters (CPPs), and Critical Quality Attributes (CQAs). CMAs\' and CPPs\' impact on identified CQAs was further assessed through a 22 full factorial experimental design at normal conditions after manufacture and one month at super-accelerated stress conditions. Results: The lead prototype exhibited no physicochemical incompatibilities. The risk assessment tools revealed that the concentration of the wetting agent and the total concentration of thickening agents represented critical factors for the quality profile of the preparation in terms of viscosity. The optimized formulation comprising 1.125 w/v% total concentration of Natrosol 250 HX and Avicel RC 591 exhibited an enhanced performance according to the established profile.
UNASSIGNED: The analytical and physicochemical tests showed the robustness and compliance of the final preparation with the quality profile. The proposed step-by-step methodology based on QbD, Design of Experiments, and Quality Risk Management presented in our research holds practical implications for local industries and formulation scientists involved in the development of oral suspensions.

This study focuses on the design, characterization, and optimization of nanostructured lipid carriers (NLCs) loaded with docetaxel for the treatment of skin cancer. Employing a systematic formulation development process guided by Design of Experiments (DoE) principles, key parameters such as particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency were optimized to ensure the stability and drug-loading efficacy of the NLCs. Combined XRD and cryo-TEM analysis were employed for NLC nanostructure evaluation, confirming the formation of well-defined nanostructures. In vitro kinetics studies demonstrated controlled and sustained docetaxel release over 48 h, emphasizing the potential for prolonged therapeutic effects. Cytotoxicity assays on human umbilical vein endothelial cells (HUVEC) and SK-MEL-24 melanoma cell line revealed enhanced efficacy against cancer cells, with significant selective cytotoxicity and minimal impact on normal cells. This multidimensional approach, encompassing formulation optimization and comprehensive characterization, positions the docetaxel-loaded NLCs as promising candidates for advanced skin cancer therapy. The findings underscore the potential translational impact of these nanocarriers, paving the way for future preclinical investigations and clinical applications in skin cancer treatment.

The Heck reaction is widely employed to build a variety of biologically relevant scaffolds and has been successfully implemented in the production of active pharmaceutical ingredients (APIs). Typically, the reaction with terminal alkenes gives high yields and stereoselectivity toward the trans-substituted alkenes product, and many green variants of the original protocol have been developed for such substrates. However, these methodologies may not be applied with the same efficiency to reactions with challenging substrates, such as internal olefins, providing trisubstituted alkenes. In the present work, we have implemented a Heck reaction protocol under green conditions to access trisubstituted alkenes as final products or key intermediates of pharmaceutical interest. A set of preliminary experiments performed on a model reaction led to selecting a simple and green setup based on a design of experiments (DoE) study. In such a way, the best experimental conditions (catalyst loading, equivalents of alkene, base and tetraalkylammonium salt, composition, and amount of solvent) have been identified. Then, a second set of experiments were performed, bringing the reaction to completion and considering additional factors. The protocol thus defined involves using EtOH as the solvent, microwave (mw) irradiation to achieve short reaction times, and the supported catalyst Pd EnCat®40, which affords an easier recovery and reuse. These conditions were tested on different aryl bromides and internal olefines to evaluate the substrate scope. Furthermore, with the aim to limit as much as possible the production of waste, a simple isomerization procedure was developed to convert the isomeric byproducts into the desired conjugated E alkene, which is also the thermodynamically favoured product. The approach herein disclosed represents a green, efficient, and easy-to-use handle towards different trisubstituted alkenes via the Heck reaction.