Design Approach For Development Research Articles

Development and validation of a method for the simultaneous estimation of terpinene-4-ol and 1,8-cineole in Melaleuca alternifolia (Maiden & Betche) Cheel and Rosmarinus officinalis L. oil using HPTLC coupled with a QbD approach

This paper comprehends a Quality by design (QbD) approach for development of a simple and precise HPTLC (High performance thin layer chromatography) method for simultaneous estimation of the phytoconstituents terpinen-4-ol and 1,8-cineole found in Melaleuca alternifolia (tea tree oil) and Rosmarinus officinalis (rosemary oil) respectively. The method was optimized by Design expert software using response surface methodology. The chromatographic condition optimized by using software was, mobile phase as hexane: ethyl acetate: glacial acetic acid in the ratio of 8.5:1.5:0.47 % v/v, stationary phase as TLC plates precoated with silica gel 60 F254 at ambient temperature conditions and saturation time 20 min at 366 nm. Optimized conditions were verified and validated as per ICH Q2 (R1) (International council for harmonization of technical requirements of pharmaceuticals for human use) guidelines. The method developed was validated for the parameters such as specificity, linearity, DL, QL, accuracy and precision. This method was then applied for simultaneous estimation of terpinen-4-ol and 1,8-cineole in Melaleuca alternifolia (tea Tree oil) and Rosmarinus officinalis (rosemary oil) respectively.

Development of an Intranasal In Situ System for Ribavirin Delivery: In Vitro and In Vivo Evaluation.

Recently, ribavirin has demonstrated effectiveness in treating glioblastoma through intranasal administration utilizing the nose-to-brain delivery route. Enhancing ribavirin's bioavailability can be achieved by utilizing intranasal stimuli-responsive systems that create a gel on the nasal mucosa. The research examined thermosensitive, pH-sensitive, and ion-selective polymers in various combinations and concentrations, chosen in line with the current Quality by Design (QbD) approach in pharmaceutical development. Following a thorough assessment of key parameters, the optimal composition of gellan gum at 0.5%, Poloxamer 124 at 2%, and purified water with ribavirin concentration at 100 mg/mL was formulated and subjected to in vivo testing. Through experiments on male rats, the nose-to-brain penetration mechanism of the active pharmaceutical ingredient (API) was elucidated, showcasing drug accumulation in the olfactory bulbs and brain.

Implementation of green-assessed nanotechnology and quality by design approach for development of optical sensor for determination of tobramycin in ophthalmic formulations and spiked human plasma

A fast eco-friendly colorimetric method was developed for the determination of Tobramycin in drug substance, ophthalmic formulations, and spiked human plasma using silver nanoparticles optical sensor. Even though tobramycin is non-UV–visible absorbing, the developed method is based on measuring the absorbance quenching of silver nanoparticles resulting from the interaction with tobramycin. Different factors affecting the absorbance intensity were studied as; silver nanoparticle concentration, pH, buffer type, and reaction time using quality by design approach. Validation of the proposed method was performed according to ICH guidelines and was found to be accurate, precise, and sensitive. The linearity range of tobramycin was 0.35–4.0 μg/mL. The optical sensor was successfully applied for the determination of Tobramycin in ophthalmic formulations and spiked human plasma without pre-treatment. Additionally, the binding between Tobramycin and PVP- capped silver nanoparticles was studied using molecular docking software. The method was assessed and compared to colorimetric reported methods for the green character using Green Analytical Procedure Index (GAPI) and Analytical GREEnness calculator (AGREE) tools and found to be greener.

Investigation the effects of operational parameters and multi-factor optimization of butene metathesis process via statistical approach

In this study, the production of propylene from 2-butene and 1-butene via the metathesis process was investigated and simulated. The effects of operational parameters, including reactor temperature, residence time, and 1-butene/2-butene molar ratio, on reactor performance were examined, and statistical models were developed. The design of experiment (DoE) was performed using the response surface methodology (RSM)-central composite design (CCD) approach for efficient experimentation and model development as well as optimization. The study's findings indicate a high conversion rate for 2-butene. By statistically analyzing the obtained data and performing analysis of variance (ANOVA), the influential parameters and their degree of importance were determined. Sensitivity analysis was conducted based on the developed models. Finally, using these models and desirability function as a powerful optimization algorithm, optimal conditions for the process were obtained. The results of the optimization showed that the maximum propylene molar fraction (32.5 %) was obtained at a temperature of 508.4 °C, a residence time of 20.7 s, and a 1-butene/2-butene molar ratio of 0.1.

Recursive Filtering Under Probabilistic Encoding-Decoding Schemes: Handling Randomly Occurring Measurement Outliers.

This article focuses on the recursive filtering problem for networked time-varying systems with randomly occurring measurement outliers (ROMOs), where the so-called ROMOs denote a set of large-amplitude perturbations on measurements. A new model is presented to describe the dynamical behaviors of ROMOs by using a set of independent and identically distributed stochastic scalars. A probabilistic encoding-decoding scheme is exploited to convert the measurement signal into the digital format. For the purpose of preserving the filtering process from the performance degradation induced by measurement outliers, a novel recursive filtering algorithm is developed by using the active detection-based method where the "problematic" measurements (i.e., the measurements contaminated by outliers) are removed from the filtering process. A recursive calculation approach is proposed to derive the time-varying filter parameter via minimizing such the upper bound on the filtering error covariance. The uniform boundedness of the resultant time-varying upper bound is analyzed for the filtering error covariance by using the stochastic analysis technique. Two numerical examples are presented to verify the effectiveness and correctness of our developed filter design approach.

Biomimetic cascade intelligent paper chip sensor based on bimetallic porphyrin-based covalent organic framework with triple-enzyme mimetic activities

Enzyme-induced biological cascade catalysis can achieve selective and efficient transformations of substrates in vivo. Thus, the biomimetic cascade systems have attracted much attention in biological detection on account of their ingenious strategies for signal conduction and amplification. In this study, a porphyrin-based covalent organic framework (COFFe/CoP-Ph) with bimetal-nitrogen-coordinate centers (M − N4) were constructed via Schiff base reaction. The synergistic effect of the highly exposed M − N4 bimetallic active sites and the unique topology overcame the self-limitation of nanozyme, resulting in a significant enhancement of the triple-enzyme mimetic activities of COFFe/CoP-Ph, namely oxidase (OXD)-, peroxidase (POD)-, and catalase (CAT)-like activities. Simultaneously, a multiple enzyme-driven cascade catalysis strategy for signal amplification was proposed utilizing the OXD- and POD-like mimetic mechanisms of COFFe/CoP-Ph, enabling the colorimetric determination of malathion without the addition exogenous H2O2. The established colorimetric sensor exhibited an exceptional linear relationship within the range of 1–18 μM and a low detection limit of 11 nM. Subsequently, a portable smartphone platform was developed by integrating paper chip, facilitating successful malathion point-of-care testing (POCT) in real samples. This work not only creates a bimetallic COF nanozyme and establishes an efficient cascade amplification strategy, but also introduces a novel design approach for development of a low-cost and user-friendly POCT method.

The Quality by design Approach for Analytical Method Development and Validation of the RP-HPLC Method for Estimation of Quercetin in Pure, Marketed, and Cream Formulation

ABSTRACT: A simple, precise reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for the flavonoid quercetin, isolated from Tridax procumbens L. The method was validated by using Phenomenex C18 (250 x 4.6mm i.d) Column. A simple, cost effective mobile phase consisting of (ACN and 10 m/moL Phosphate buffer as mobile phase in proportion of 50:50 v/v ) pH 3, 1.0 ml/min Flow rate at 370nm by using UV Visible detector. The retention time of Quercetin was found to be 3.392 minutes. The Quercetin linearity range was found to be 05 to 25 μg/mL. The accuracy and precision of commercially available preparations and in-house cream formulations were investigated using a one-way ANNOVA test. The Percentage recovery of both formulations was found to be 99.83%, 99.88%, 99.82% and 98.92%, 98.18%, 98.86%. Robustness of analytical method was studied by using 2/3 full factorial design by using Design expert software. The Percentage assay and % RSD of marketed capsule and in house cream was found to be 98.38 %, 97.40% and 0.05273, 0.02053 respectively. The Limit of Quantitation and Limit of detection were found to be 0.9053μg/mL and 2.5435μg/mL respectively. The development method of quercetin is simple, accurate, precise, sensitive, and robust

Implementation of Quality by Design approach for Development of Optimized Drug Delivery System of Antidepressant Drug

The work presented aimed to implement of “Quality by Design” (QbD) approach to develop optimized fast dissolving tablet (FDT) of Fluoxentine. A face centered Central composite design was employed to develop optimized dosage form. FDTs were prepared by direct compression followed using sublimation technique with additive effect of super disintegrants. Impact of independent variables such as concentration of super-disintegrant and sublimating agent was determined on dependent variables i.e. wetting time, disintegration time and drug release. Data optimization was done by developing validation check batches as well as overlay plot developed by statistical software. Optimized formulation shows 18.08 s wetting time (WT), 19.84 s disintegration time (DT) and the drug release was found to be 85.82 % in 5 m. The accelerated stability studies for optimized FDTs shows no significant changes during one month stability studies. In conclusion, the optimized fast dissolving tablets for Fluoxentine was successfully developed employing by QbD approach with least utilization of man, money and efforts.

Characterization of mechanical properties, efficiency, and design considerations for the additive manufacturing of hybrid composites with continuous fibers

The integration of continuous fibers into additively manufactured plastic components greatly enhances their mechanical properties. Nonetheless, a challenge lies in the limited adaptability of these properties to specific loading scenarios. To address this issue, present research aims to exploit the hybridization of additively manufactured composites, combining diverse fiber materials within a single component. Specifically, fabricating continuous fiber-reinforced hybrid composites through material extrusion enables high flexibility in adapting local fiber materials. To further the understanding of the effects of hybrid fiber reinforcement in additively manufactured plastic parts, this study investigates how distinct stacking sequences in hybrid and non-hybrid PA6-based composite components, reinforced with carbon and glass fibers, affect deformation and failure behavior. Mechanical properties are assessed using tensile, flexural, and impact tests, in conjunction with an analysis of cost and weight efficiency. The results unveil a distinct correlation between stacking sequences and the mechanical properties of additively manufactured composites. While the hybrid samples predominantly exhibit slight negative hybrid effects, a positive hybrid effect of 96.4 % is achieved in terms of impact toughness with an optimized stacking sequence. With the exception of impact strength, specimens reinforced solely with carbon fibers frequently demonstrate a remarkable ratio between mechanical properties, weight, and cost, whereas hybrid composites exhibit a balanced compromise across all tested mechanical properties. Building upon the obtained results, three comprehensive design approaches are introduced and applied, demonstrating the new design possibilities arising from the combination of hybrid composites and additive manufacturing. The developed design approaches and material combinations can be used for a wide range of lightweight construction applications.

Quality by design approach for development and characterization of gabapentin-loaded solid lipid nanoparticles for intranasal delivery: In vitro, ex vivo, and histopathological evaluation.

"Quality by Design" (QbD) is a novel approach to product development that involves understanding the product and process, as well as the relationship between critical quality attributes (CQA) and critical process parameters (CPP). This study aimed to optimize the gabapentin-loaded solid lipid nanoparticle formulation (GP-SLN) using a QbD approach and evaluate in vitro and ex vivo performance. The GP-SLN formulation was created using the microemulsion method by combining Gelucire 48/16, Tween 80, and Plurol Oleique CC 497. The Box-Behnken experimental design was adopted to investigate the effects of independent factors on dependent factors. The GP-SLN formulation was assessed based on particle size and distribution, zeta potential, morphology, entrapment efficiency, release kinetics, permeation parameters, stability, and nasal toxicity. The nanoparticles had a cubical shape with a particle size of 185.3±45.6 nm, a zeta potential of -24±3.53 mV, and an entrapment efficiency of 82.57±4.02%. The particle size and zeta potential of the GP-SLNs remained consistent for 3 months and followed Weibull kinetics with a significantly higher ex vivo permeability (1.7 fold) than a gabapentin solution (GP-SOL). Histopathology studies showed that intranasal administration of the GP-SLN formulation had no harmful effects. The current study reports the successful development of a GP-SLN formulation using QbD. A sustained release of GP was achieved and its nasal permeability was increased. Solid lipid nanoparticles with optimum particle size and high entrapment efficiency may offer a promising approach for the intranasal delivery of drugs.

Quality by design approach for development and optimization of rifampicin loaded nanoparticles and characterization

Background: Rifampicin is an effective in the treatment of sensitive, non-resistant strains of mycobacterium tuberculosis. Thus there is need to develop a rifampicin loaded nanoparticles. Aim: This study is focused on development of RFM loaded nanoparticles, characterization to achieve lung targeting using quality by design approach. Objectives: The main objective of this study is optimizing particle size and entrapment efficiency of rifampicin-loaded nanoparticles and making them suitable for nebulizer application using QbD approach. Methods: Quality target product profile was defined along with critical quality attributes for the formulation. Preparation of nanoparticle dry powder inhaler formulation were numerous methods such as microemulsion solvent evaporation, ionic gelation and modified ionic gelation followed by probe sonication were employed for the preparation of nanoparticles and the final method of preparation was selected based on particle size, zeta potential, entrapment efficiency and drug loading. Results: The optimized RFM-loaded nanoparticles were characterized by UV spectroscopy, FTIR, DSC techniques. The observed nanoparticles were spherical in shape. The TPP concentration, stirring speed and concentration of acetic acid were playing a crucial role in the successful formation of nanoparticles and were selected for optimization. In vitro release study showed 100% release of pure RFM within 12 hrs and the optimized chitosan nanoparticle formulation loaded with RFM showed nearly 90% release of RFM within 24 hr. Conclusion: Rifampicin loaded nanoparticle DPI formulations achieve lung targeting and the delivery of drug into the lungs will also prevent the first pass metabolism, thus, leading to reduction in the dose of the drug as well as related side effects. These drug targeting approaches may serve as a boon in the effective treatment of tuberculosis.

Implementation of Quality by Design Approaches for Development and Validation of Reverse-Phase High-Performance Liquid Chromatography Assay Method for Determination of Glycyrrhizin in Nanoformulation.

Glycyrrhizin (GL) is the principal constituent of Glycyrrhiza glabra, having antiallergic, anticancer, anti-inflammatory, and antimicrobial action. The reverse-phase high-performance liquid chromatography (RP-HPLC) analytical method was used to quantitatively estimate GL in a nanoformulation and validated as per International Conference on Harmonization Q2 (R1) standards. A stationary phase of the C18-HL reversed-phase column and a mobile phase of acetonitrile and water were used for effective elution. The chromatographic conditions of RP-HPLC were optimized utilizing a quality-by-design approach to accomplish the required chromatographic separation of GL from its nanoformulation with minimal experimental runs. Optimized RP-HPLC conditions for the assay method consist of acetonitrile (41%) and water, pH 1.8, balanced with phosphoric acid (0.1%) as a mobile phase with a flow rate of 1 mL/min. The retention time was found at 7.25 min, and method validation confirmed its sensitivity, preciseness, accuracy, and robustness.

Community‐informed design: Blending community engagement and museum design approaches for sustainable experience development

AbstractThe museum field currently and historically has centered on the needs of White, educated, privileged, and affluent people, and changing that reality requires new ways of conceptualizing, organizing, and assessing our core practices. Practice‐based models—including specific stories of how museums and communities work together—are still needed in our field, both as guidance for structuring future projects and as inspiration for what is possible. We share a case study of a 10‐year makerspace design process and identify key features for sustaining community–museum relationships over an extended period of work, which we call community‐informed design. We describe five key aspects that promote sustainability in terms of community–museum relationships and the creation of high‐quality experiences: naming values and assumptions, emergent planning, flexible and distributed staffing, organization‐to‐organization relationships, and layered data.

Enhancing analytical development in the pharmaceutical industry: A DoE-QSRR model for virtual Method Operable Design Region assessment

Recently, the pharmaceutical industry has increasingly adopted the Analytical Quality by Design (AQbD) approach for analytical development. To facilitate AQbD approach implementation in the development of chromatographic methods for determining cephalosporin antibiotics, an in silico tool capable of performing virtual DoEs was developed enabling to obtain virtual operable regions of method. To this end, the drugs cephalexin, cefazolin, cefotaxime and ceftriaxone were analyzed using four experimental designs, deriving a DoE-QSRR model and employing Monte Carlo method. The DoE-QSRR model and virtual DoEs were validated using data not used in model's construction, obtaining coefficients of determination of 84.72 % for DoE-QSRR model and over 77 % for virtual DoEs. Virtual MODRs were constructed using data from the virtual DoEs. The virtual MODRs were validated by comparing them with experimental MODRs under various scenarios, with overlap areas reaching values exceeding 84 %. Therefore, the in silico tool was considered suitable for indicating analyte trends under different analytical conditions, being capable of performing virtual DoEs for cephalosporin drugs with sufficient assertiveness to guide analytical development and allow obtaining a MODR capable of providing results of adequate quality.

Experimental design approach for development of carboplatin loaded chitosan modified liposomal formulation with improved topical vaginal therapeutic potential

One of the most prevalent cancers affecting women globally is cervical cancer. Cervical cancer is thought to cause 570 000 new cases annually, and standard treatments can have serious side effects. In this work, the main aim is to design, fabrication, and evaluation of carboplatin loaded chitosan coated liposomal formulation (CCLF-I) for vaginal delivery in the treatment of cervical cancer. The particle size and polydispersity index of the CCLF-1 were observed at 269.33 ± 1.15 and 0.40 ± 0.002 nm, respectively. The in vitro mucin binding studies showed good adhesiveness of CCLF-I as compared to plain liposomes (CPLF-I), which was found at 23.49 and 10.80%, respectively. The ex-vivo percent drug permeation from plain liposomal formulation (CPLF-I) was found to be higher in comparison to chitosan coated liposomal formulation which was 56.33% while in CCLF-I it was observed 47.32% this is due to, higher retainability of delivery system (CCLF-I) on targeted site attained by coating of mucoadhesive polymer on liposomes. Ex vivo tissue retention studies exhibited 24.2% of CCLF-I in comparison to 10.34% from plain drug formulation (CPLF-I). The in vivo vaginal retention studies exhibited 14% of drug retention after 24 h from the novel formulation in comparison to 6% from the plain formulation. The developed CCLF-I formulation would open a new avenue in the cervical treatment.

Quality by Design Approach for Development and Characterization of Granisetron Hydrochloride-Loaded Orodispersible Films

AbstractGranisetron hydrochloride can be used to prevent and treat nausea and vomiting induced by chemotherapy. Its prolonged half-life and reduced dose requirement improve patient acceptance. However, patients undergoing chemotherapy often suffer from dysphagia and drug spitting due to emesis. Hence, the development of a patient-centered formulation of granisetron hydrochloride with simple medication and high compliance is crucial. The current study employed a polymer combination of polyvinylpyrrolidone/polyvinyl alcohol (PVP/PVA) as film-forming materials and Lycoat® RS 780 as a disintegrant to formulate orodispersible films (ODFs) loaded with granisetron hydrochloride. Guided by the concept of quality by design, the quality target product profile and critical quality attributes (CQAs) for the ODF were defined. Through the quality risk assessment, essential factors that have a significant impact on CQAs were identified. The formulation was screened using the Box–Behnken statistical design with three factors and three levels. Our data suggested that all ODF formulations exhibited a disintegration time of less than 60 seconds and complete dissolution within 5 minutes. Furthermore, the formulation displayed appropriate mechanical properties, water residue, and pH values. Thus, the granisetron hydrochloride-loaded ODF is regarded as a patient-friendly formulation that enhances compliance and consequently aids in therapeutic effectiveness.

Molecular Dynamics Simulations of HDAC-Ligand Complexes Towards the Design of New Anticancer Compounds±.

Quantitative Structure-Activity Relationship (QSAR) studies gained a foothold in the mid-1960s to rationalise the biological activity of medicinally important compounds. Since then, the advancements in computer hardware and software added many new techniques and areas to this field of study. Molecular dynamics (MD) simulations are one such technique in direct drug design approaches. MD simulations have a special place in drug design studies because they decode the dynamics of intermolecular interactions between a biological target and its potential ligands/inhibitors. The trajectories from MD simulations provide different non-bonding interaction parameters to assess the compatibility of the protein-ligand complex and thereby facilitate the design of prospective compounds prior to their wet-lab exploration. Histone deacetylases (HDACs) play a key role in epigenetics and they are promising drug targets for cancer and various other diseases. This review attempts to shed some light on the modelling studies of HDAC inhibitors as anticancer agents. In view of the advantages of MD simulations in direct drug design, this review also discusses the fragment-based approach in designing new inhibitors of HDAC8 and HDAC2, starting from the interaction energies of ligand fragments obtained from the MD simulations of respective protein-ligand complexes. Here, the design of new anticancer compounds from largazole thiol, trichostatin A, vorinostat, and several other prototype compounds are reviewed. These studies may stimulate the interest of medicinal chemists in MD simulations as a direct drug design approach for new drug development.

Analytical Quality by Design (QbD) Approach for Development and Validation of HPLC Method for Acyclovir: Application Degradation Kinetics

Investigations on chemical behaviour of Acyclovir (ACY) are essential for determining stability properties during processing and storage conditions. The present work describes the stability and decomposition kinetics of ACY by using a stability indicating HPLC method. The experiments were designed with quality by design (QbD) approach to facilitate method development and optimization. Different stress conditions including hydrolytic (acid, base, neutral), oxidative, thermal and photolytic degradation were applied. Stability analysis reveals that relevant degradation occurs in all applied conditions. The proposed method was linear with precision and robustness values within acceptable limits.Under employed experimental conditions, the degradation of ACY followed (pseudo) first-order kinetics. The kinetic parameters (rate constant, t1/2, and t90) of the degradation of ACY were calculated.

An Experimental Design Approach for Development of Crocin-Loaded Microparticles Embedded in Gelatin/Oxidized Alginate-Based Hydrogel

An Experimental Design Approach for Development of Crocin-Loaded Microparticles Embedded in Gelatin/Oxidized Alginate-Based Hydrogel

Application of Principal Component Analysis and DoE-Driven Green Analytical Chemistry Concept to Liquid Chromatographic Method for Estimation of Co-formulated Anti-Hypertensive Drugs.

The fixed-dose combination (FDC) of metoprolol succinate (MTS), cilnidipine (CDN), and telmisartan (TST) is used for the management of hypertension. Numerous reversed phase (RP)-HPLC methods have been reported in the literature for chromatographic analysis of MTS, CDN, and TST. According to the concept of green analytical chemistry (GAC), toxic organic solvents should be avoided or minimized during chromatographic method development for the safety of analysts and the protection of the environment. The reported RP-HPLC methods have been developed using acetonitrile (ACN) or methanol as an organic component of the mobile phase and diluent for sample preparation. These organic solvents are considered toxic solvents as per the International Council for Harmonization (ICH) Q3C (R6) guideline and Pfizer medicinal chemistry solvent selection (PMCSS) guide. We aimed to develop an environment-friendly and economical RP-HPLC-photo-diode array (PDA) method for the analysis of MTS, CDN, and TST using less toxic organic solvents to support the concept of GAC. The method development was carried out by the implementation of chemometrics and design of experiments (DoE) to avoid wastage of organic solvent. Principal component analysis (PCA) was applied as a chemometric tool for the identification of critical method risk variables (MRVs) and method performance attributes (MPAs). The identified critical MRVs and MPAs were further studied by DoE-based response surface modelling for optimization of the method. The chromatographic analysis of MTS, CDN, and TST was carried out using a Shim-pack ODS column as a stationary phase and ethanol as an organic modifier in the mobile phase. The developed method was applied to the assay of FDCs and results were found to be in compliance with the label claim. The greenness profiles of reported and present RP-HPLC methods were evaluated by national environmental method index (NEMI) and analytical greenness (AGREE) methods. The developed method was found to be green, robust, and economical as compared to published methods for the analysis. Development and validation of an RP-HPLC method for simultaneous estimation of MTS, CDN, and TST using safe organic solvents. Implementation of a analytical quality by design (AQbD) approach in method development using PCA and DoE. Application of the method for assay of FDCs of MTS, CDN, and TST.