Systematic Implementation of Quality by Design (QbD): A Perspective from Generic Pharmaceutical Industries

Objective: The objective of this study was to develop a polymeric composite of the poorly soluble antidepressant drug felodipine with help of PVP K-30 and PEG 6000, using a Quality by Design (QbD) approach to enhance its solubility and, consequently, its bioavailability. Methods: In this work, the quality target product profile (QTTP) was defined and Critical Quality Attributes (CQAs) were identified. Additionally, risk assessment analyses were carried out using the Ishikawa fishbone diagram to identify the Critical Material Attributes (CMAs) and/or Critical Process Parameters (CPPs) associated with the development of polymeric composite that could influence the Critical Quality Attributes (CQAs) of the drug product. The solubility of felodipine hydrochloride was improved by creating various polymeric composites with various concentrations of Poly Vinyl Pyrrolidone K30 (PVP-K 30) and Poly Ethylene Glycol 600 (PEG 600) by solvent evaporation method as Critical material attribute (CMA) as identified by risk assessment study and the and CQAs viz drug solubility, drug content and drug release. These composites were designed using a 32 Face Central composite Design (FCCD) with a face-centered approach implemented in Design Expert software. Results: After defining QTTP and CQA, risk assessment analysis was successfully used to identify CMA as well as CPPs. A total of thirteen PVP-PEG polymeric composites were developed and evaluated for FTIR spectra, Differential Scanning Colorimetry (DSC), X-Ray diffraction (XRD), and Scanning electron Microscopy (SEM). Data optimization was performed using response surface methodology, including contour and overlay plots. Solubility, drug content, and drug release of the optimized batch were found to be 21.55 mg/ml, 100%, and 78.314%, respectively. Three Validation Check batches (VC1-VC3) were developed and validated. Percent error for solubility ranges between-0.0019 to 0.0061, drug content ranges between 0.0005 to 0.0031 and solubility ranges between 0.0005 to 0.0011 that were very close to the predicted value, hence verifying the optimized data. Thus, by carefully using the QbD technique, the solubility of felodipine was enhanced by the effective development of a PVP-PEG polymeric composite. Conclusion: The QbD approach was to be an effective tool to develop an optimized polymeric composite of PVP 30K and PEG 6000 of felodipine with improved solubility without exhaustive research.

Background: Nowadays, many small-volume injection products are circulating on the market. Small-volume parenteral (SVP) products are usually designed for treatment purposes that provide systemic effects. If it is not produced strictly, the product will be hazardous and even life-threatening. Quality assurance is one of the primary tools used to ensure the acceptable performance of SVP products. Quality by design (QbD) represents a systematic strategy for product development that starts with setting a target product quality and emphasizes product process control based on a scientific approach and quality risk assessment. The purpose is to ensure SVP product quality from design to production process. Objective: This review will determine generally Critical Quality Attributes (CQA), Critical Material Attributes (CMA), and Critical Process Parameters (CPP) in terms of explaining the quality assurance of SVP products with a quality-by-design approach. Methods: All articles were obtained by electronic search using ICH guidelines, Science Direct, and Google Scholar. Results: From the literature review, it was found that using a quality-by-design approach through integrated CQA, CMA, and CPP can produce SVP products that comply with QTPP (Quality Target Product Profile) and regulatory requirements. Conclusion: QbD has been established as a valuable scientific approach for ensuring quality assurance within the pharmaceutical industry. Pharmaceutical companies prioritize obtaining regulatory approval before introducing any product to the market. Keywords: Critical Process Parameter; Critical Quality Attributes; Quality by Design; Parenteral; Small Volume Parenteral.

Pharmaceutical has vast areas of formulation and development which design different formulations for different disease conditions and their treatment. Each product developed in the pharmaceutical has to pass the standard prescribed in the monographs. QbD plays an important role in drug product development that is very important because it ensures the stability, safety, and quality of the product. The product quality should be best so that it has per patient compliance. QbD ensures all the safety procedures in the industries that make the stable and good quality and validate the procedure. It also helps in the design of the product and its procedures. It controls all the manufacturing processes and understanding that develops the best quality product. Its modern approach in the pharmaceuticals which aims to develop and design a quality product using its manufacturing process that is intended to deliver constantly and shows good performance. Quality by Design (QbD) is a methodical approach to drug development that emphasizes comprehending and managing the production process to guarantee constant product quality. Critical Quality Attributes (CQAs), Critical Material Attributes (CMAs), and Critical Process Parameters (CPPs) are all identified in this examination, which offers a thorough summary of QbD concepts. It talks about how to optimize pharmaceutical formulations and manufacturing processes by using risk assessment tools, Design of Experiments (DoE), and multivariate analysis. It is emphasized how important regulatory guidelines—like those provided by the International Council for Harmonization (ICH) Q8–Q11—are to maintaining compliance and improving product lifecycle management. Additionally, the study examines how QbD might enhance product effectiveness, lower variability, and speed up regulatory approvals. The difficulties in putting QbD into practice, such as the lack of resources and the complexity of data processing, are also discussed. Insights into the strategic application of QbD to improve pharmaceutical product development and production are the goal of this research.

Flutamide which isused to treat prostate cancer and other diseases induces liver damage during and after the therapy. The aim of this study was to develop a flutamide/piperineco-loaded self-emulsifying drug delivery system (FPSEDDS) to inhibit flutamide-induced liver injury by utilizing piperine as a metabolic inhibitor. The development of SEDDS was carried out following a quality by design (QbD) approach. The risk assessment study was performed to identify critical quality attributes (CQAs) and critical material attributes (CMAs)/critical process parameters (CPPs). I-optimal mixture design was executed with three CMAs as the independent variables and CQAs as the dependable variables. The effectiveness of optimized SEDDS to circumvent flutamide-induced hepatotoxicity was assessed in mice. The numerical optimization suggested an optimal formulation with a desirability value of 0.621, using CQAs targets as optimization goals with 95% prediction intervals (α = 0.05). The optimal formulation exhibited the grade A SEDDS characteristics with the guarantee of high payloads in self-formed oily droplets. The design space was also obtained from the same optimization goals. All CQA responses of verification points were found within the 95% prediction intervals of the polynomial models, indicating a good agreement between actual versus predicted responses within the design space. These obtained responses also passed CQAs acceptance criteria. Finally, hematoxylin-eosin staining revealed the minimal flutamide-induced hepatotoxicity from the optimal SEDDS formulation as compared to the control and flutamide/piperine normal suspension. We demonstrate that the piperine containing optimized SEDDS formulation developed by QbD significantly reduces the flutamide-induced liver injury in mice.

The aim of our research work was to develop dermally applicable, semisolid film-forming systems (FFSs) containing silicones, which form a film on the skin in situ, with suitable mechanical properties for skin application. FFSs were developed and investigated by means of the Quality by Design (QbD) methodology. With this QbD approach, the initial risk assessment defines the critical quality attributes (CQAs), the critical material attributes (CMAs) and the critical process parameters (CPPs) to ensure the required quality. Different semisolid systems were formed with or without silicones. During the initial risk assessment, three CQAs, namely skin adhesion, film flexibility and burst strength, were found to be critical attributes, while film appearance, film integrity and the drying time of the semisolid system, were found to be medium attributes. These parameters were investigated. The initial risk assessment also showed that there are three high CMAs: the type of silicones, film-forming excipients, drying excipients, and that there was one medium CMA: viscosity-enhancing excipients. Based on our results, the silicone content had a great effect on the film-forming systems. Different silicones affected the mechanical properties of the films in varying ways, decreased the drying time and showed promising results regarding the drying mechanism.

Background: Polymeric nanoparticles (PNPs) have emerged as promising drug delivery systems to overcome the limitations of conventional chemotherapeutics. Capecitabine, a prodrug of 5-fluorouracil (5-FU), is widely used in cancer therapy but suffers from poor bioavailability and systemic toxicity. The appli-cation of the Quality by Design (QbD) framework in PNP development provides a structured approach to address these challenges. Objective: This review examines the QbD principles in the formulation and optimization of capecitabine-loaded PNPs, focusing on strategies to enhance therapeutic efficacy and minimize adverse effects. Methods: The QbD approach encompasses defining a Quality Target Product Profile (QTPP), identifying Critical Quality Attributes (CQAs), and conducting risk assessments to pinpoint Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs). Techniques such as Design of Experiments (DoE) facilitate systematic optimization. Results: Incorporating QbD principles ensures the development of robust PNP formulations with improved encapsulation efficiency, controlled drug release, and targeted delivery. Studies highlight the use of biodegradable polymers like PLGA, chitosan, and PEG for superior biocompatibility and stability. Analytical methods validate the consistency and quality of the nanoparticles. Conclusion: The QbD framework enables the rational design of capecitabine-loaded PNPs with enhanced bioavailability and reduced toxicity, contributing to safer and more effective cancer treatments. Future research should explore novel polymeric systems and advanced manufacturing technologies to expand the therapeutic potential of PNPs in oncology.

Objective Over the last few decades, there have been advancements in our comprehension of the design and development of topical semisolid formulations; however, they still follow an empirical development. Our study focuses on building a framework for designing and developing topical semisolid products using ‘Quality by Design’ (QbD) approach. Methods A literature review was conducted to identify and list the factors related to the design and development of topical semi-solid dosage forms using Quality by Design approach. The information extracted from the relevant articles was used to build a QbD framework based on four main pillars: Define the Quality Target Product Profile (QTPP); identify Critical Quality Attributes (CQAs); identify Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs); understand how CMAs and CPPs affect CQAs and establish a control strategy. Results Some typical elements of the QTPP for topical products include dosage form, route of administration, shelf life, critical quality attributes of the final formulation. Critical material attributes such as characteristics of API (molecular weight, lipophilicity, solubility, metamorphosis events, and polymorphism), characteristics of excipients, and critical process parameters (temperature, heating and cooling rates, mixing speed, pumping speed, order of addition) are identified and explained for their impact on CQAs. Conclusions Proper characterization of the API and drug delivery system will increase the likelihood of developing a stable, pleasing, and tolerable topical formulation and minimize the risk of failure.

Quality by design (QbD) optimization of diazepam-loaded nanostructured lipid carriers (NLC) for nose-to-brain delivery: Toxicological effect of surface charge on human neuronal cells

Quality by Design (QbD) is an approach encouraged by regulatory bodies and applied by pharmaceutical industries to improve the quality of the final product. The objective of this paper is to describe via a QbD approach the available knowledge on the formulation and manufacturing of solid lipid nanoparticles (SLN) for ocular applications using hot high pressure homogeniser (HPH). The formulation of SLN for the ocular delivery of a hydrophilic peptide is discussed based on a QbD perspective, where the knowledge is gathered from literature references. The Quality Target Product Profile (QTPP) is defined, followed by a description of the Critical Quality Attributes (CQA) and Critical Material Attributes (CMA). After having described the manufacturing process via hot HPH, the Critical Process Parameters (CPP) are discussed along with the possible control strategies. The QbD approach for the development of a SLN for ocular application described in this review paper can be used as starting point for similar applications.

Development of nanostructured lipid carriers containing salicyclic acid for dermal use based on the Quality by Design method

Oral administration is the most preferred route for drug delivery due to its convenience, non-invasiveness, and patient compliance. However, it is challenged by gastrointestinal barriers, enzymatic degradation, and first-pass metabolism, which reduce drug bioavailability. Lipid nanoparticles (LNPs), including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), offer a promising strategy to overcome these limitations by enhancing drug stability, permeability, and absorption. The Quality by Design (QbD) framework provides a systematic approach for LNP development to ensure consistent product quality. By promoting process understanding and control, QbD not only supports scientific formulation development but also enhances industrial scalability by reducing the experimental workload, shortening the development time, and lowering the production costs. This review highlights key QbD elements such as the quality target product profile (QTPP), critical quality attributes (CQAs), critical material attributes (CMAs), critical process parameters (CPPs), and design of experiments (DoE) and their roles in guiding formulation and process optimization. The effects of various CMAs and CPPs on the CQAs such as particle size, polydispersity index, encapsulation efficiency, zeta potential, and drug release are discussed. Furthermore, the in vitro, in vivo, and ex vivo performances of optimized LNPs were explored in detail. Overall, QbD offers a robust platform for the rational design and scalable production of high-quality lipid-based drug delivery systems for oral administration.

Implementation of quality by design principles in the development of microsponges as drug delivery carriers: Identification and optimization of critical factors using multivariate statistical analyses and design of experiments studies

Quality by design (QbD) is an essential part of the modern advance to pharmaceutical quality. Quality has been given an importance by all regulatory body for pharmaceutical products. Quality means customer satisfaction in terms of service, products, and process. QbD is best key to build a quality in all pharmaceutical products. This paper gives idea about the Pharmaceutical Quality by Design (QbD) and describes use of Quality by Design to ensure quality of Pharmaceutical Analysis. Under this concepts of be throughout design and growth of product, it is important to identify desire product performance report Target product profile (TPP), Quality Target product profile (QTPP) and identify critical quality attributes (CQA). To recognize the impact of raw material critical material attributes (CAM), critical process parameters (CPP) on the CQAs and identification and control sources of changeability. USFDA launched a pilot programme in 2005 to permit participating firms a prospect to submit chemistry, manufacturing, and controls (CMC) of NDA information representing application of QbD. QbD has its perspectives to contribute the drug design, development, and manufacture of high-quality drug products. In the present review basic consideration of the QbD approach, its historical background, and regulatory needs are discussed. In detail explanation of elements of QbD i.e. method intent, design of experiment, and risk assessment is given. The foundation of Quality by Design is ICH Guidelines. It is based on the ICH Guidelines Q8 for pharmaceutical development, Q9 for quality risk management, Q10 for pharmaceutical quality systems. It also gives application of Quality by Design in pharmaceutical development and manufacturing of pharmaceuticals. Keywords: Quality by design, Critical Quality Attributes, Pharmaceutical Analysis, Design Of Experiment, Risk Assessment, Regulatory.

Pharmaceutical development is revolutionized by the Quality by Design (QbD) strategy, which replaces conventional trial-and-error procedures with a systematic, science-based approach that ensures product quality, safety, and efficacy. This article offers a comprehensive description of the key elements and instruments required to execute QbD, as specified by regulatory recommendations like ICH Q8 (R2) and ICH Q9. The construction of a Target Product Quality Profile (TPQP), which acts as a dynamic summary of the quality attributes required to achieve the intended product quality, safety, and efficacy, is the basic concept of quality-based development (QbD). Critical quality attributes, or CQAs that are, are important qualities that need to be maintained within specified limits in order to ensure the quality of the final product. These are connected to Critical Process Parameters (CPPs) and Critical Material Attributes (CMAs) via risk assessment techniques like Fault Tree Analysis (FTA) and Failure Mode Effects Analysis (FMEA). An essential component of Quality-Based Development (QbD) is Quality Risk Management (QRM), which offers a framework for evaluating and controlling risks over the course of a product's existence. To identify and reduce potential risks, a variety of tools are used, such as Hazard Analysis and Critical Control Points (HACCP), FMEA, and FTA. The foundation of Quality-Based Design (QbD) is the idea of Design Space, which is described as the multifaceted collection of variable inputs and process factors that ensures quality assurance. Another crucial element of QbD is Control Strategy, which consists of a series of planned controls based on knowledge about present products and processes. The concepts of lifecycle management and continuous improvement highlight the significance of implementing a pharmaceutical quality system at every stage of the product lifecycle in order to encourage innovation and continuous improvement while assuring regulatory compliance. The principles of Quality by Design (QbD) are applied with the use of several technologies, including Process Analysis Technologies (PAT) and Design of Experiments (DOE). These technologies allow for the real-time monitoring and management of critical process parameters, which reduce manufacturing unpredictability and increase product quality.

Quality by design (QbD) is a systematic, scientific, risk-based approach to product development and manufacturing process to consistently deliver the quality product. In this chapter, application, benefits, opportunities, regulatory requirements involved in quality by design of pharmaceutical products are discussed. In quality by design approach, during development, the developer defines quality target product profile (QTPP) and identifies critical quality attributes (CQA). Critical process parameters (CPP) of unit operations which impacts critical quality attributes need to be identified to understand the impact of critical material attributes (CMA) on quality attributes of the drug product. Quality by design approach is defined in ICH guidelines Q8 – Pharmaceutical Development, Q9 – Quality Risk Management, Q10 – Pharmaceutical Quality System. This chapter describes the implementation of new concepts in quality by design like design of experiments to achieve design space, control strategy to consistently manufacture quality product throughout the product lifecycle.