QbD

The focus of this paper is on queueing models with arrivals from several sources, where the number of waiting spaces for each arrival source is finite. The main distinction from prior studies is that in our models waiting spaces are separate. Within this context, we examine the benefit of pooling, regardless of whether arrival rates are equal or different. We present a Quasi-Birth-and-Death (QBD) model to address the general case, with simplified versions tailored to specific scenarios. One practical application of the proposed models can be found in the loading and unloading processes at container terminals...

This study explores a novel approach to address the challenges of delivering highly water-soluble drug molecules by employing hydrophobic ion-pairing (HIP) complexes within poly (lactic-co-glycolic acid) (PLGA) microspheres. The HIP complex, formed between doxycycline hyclate (DH) and docusate sodium (DS), renders the drug hydrophobic. The development of the microspheres was done using the QbD approach, namely, Box-Behnken Design (BBD). A comprehensive characterization of the HIP complex confirmed the successful conversion of DH...

Osteoporosis is a metabolic disorder that leads to deterioration of bones. The major challenges confronting osteoporosis therapy include early-stage detection and regular disease monitoring. The present studies employed D-aspartic acid octapeptide (-D-Asp-)8 as bone-targeting peptide for evaluating osteoporosis manifestation, and superparamagnetic iron oxide nanoparticles (SPIONs) as nanocarriers for MRI-aided diagnosis. Thermal decomposition technique was employed to synthesize SPIONs, followed by surface-functionalization with hydrophilic ligands...

Based on the concept of quality by design(QbD), this study optimized the processing technology of Ilicis Rotundae Cortex. According to the processing method and ingredient requirements of Ilicis Rotundae Cortex in the Chinese Pharmacopoeia, the content of syringin and pedunculoside, alcohol extract, fragmentation rate, and moisture content were taken as the critical quality attributes(CQAs). The soaking time, moistening time, and drying time were taken as critical process parameters(CPPs) by single factor tests...

Quality by design (QbD) serves as a systematic approach to pharmaceutical development, beginning with predefined objectives and emphasizing an understanding of the product based on sound science and risk management. The purpose of this study is to utilize the QbD concept to develop a stable peptide-loaded long-acting injection formulation. An in-depth comprehension of peptide degradation mechanisms was achieved through forced degradation investigations, elucidating (acid) hydrolysis and oxidation as the primary degradation pathways for the peptide ACTY116...

Carvedilol (CV), a β-blocker essential for treating cardiovascular diseases, faces bioavailability challenges due to poor water solubility and first-pass metabolism. This study developed and optimized chitosan (CS)-coated niosomes loaded with CV (CS/CV-NS) for intranasal (IN) delivery, aiming to enhance systemic bioavailability. Utilizing a Quality-by-Design (QbD) approach, the study investigated the effects of formulation variables, such as surfactant type, surfactant-to-cholesterol (CHOL) ratio, and CS concentration, on CS/CV-NS properties...

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M.tb) and is the second leading cause of death from an infectious disease globally. The disease mainly affects the lungs and forms granulomatous lesions that encapsulate the bacteria, making treating TB challenging. The current treatment includes oral administration of bedaquiline (BDQ) and pretomanid (PTD); however, patients suffer from severe systemic toxicities, low lung drug concentration, and non-adherence. In this study, we developed BDQ-PTD loaded nanoparticles as inhalable dry powders for pulmonary TB treatment using Quality-by-Design (QbD) approach...

Recently, nanobiomaterials have been explored for improved biological activities and value addition to the herbal extracts. Zein is a natural biopolymer with excellent pharmaceutical characteristics for topical applications. Moringa oleifera plant possesses large number of phytopharmaceuticals and its leaves are used in wound healing since ancient time. In this study, we studied first time, encapsulation of Moringa oleifera leaves aqueous extract into zein nanoparticles which are developed and optimized using quality by design approach...

Mono or dual chitosan oligosaccharide lactate (COL)-conjugated pluronic F127 polymers, FCOL1 and FCOL2 were prepared, self-assembled to form micelles, and loaded with gatifloxacin. The Gati@FCOL1/Gati@FCOL2 micelles preparation process was optimized by QbD analysis. Micelles were characterized thoroughly for size, CMC, drug compatibility, and viscosity by GPC, DLS, SEM, IR, DSC, and XRD. The micelles exhibited good cellular uptake in both monolayers and spheroids of HCEC. The antibacterial and anti-biofilm activities of the micelles were evaluated on P...

Antibody-drug conjugates (ADCs) comprise an antibody, linker, and drug, which direct their highly potent small molecule drugs to target tumor cells via specific binding between the antibody and surface antigens. The antibody, linker, and drug should be properly designed or selected to achieve the desired efficacy while minimizing off-target toxicity. With a unique and complex structure, there is inherent heterogeneity introduced by product-related variations and the manufacturing process. Here this review primarily covers recent key advances in ADC history, clinical development status, molecule design, manufacturing processes, and quality control...

Enabling real-time monitoring and control of the biomanufacturing processes through product quality insights continues to be an area of focus in the biopharmaceutical industry. The goal is to manufacture products with the desired quality attributes. To realize this rigorous attribute-focused Quality by Design approach, it is critical to support the development of processes that consistently deliver high-quality products and facilitate product commercialization. Time delays associated with offline analytical testing can limit the speed of process development...

The past years have sharpened the industry's understanding of a Quality by Design (QbD) approach toward clinical trials. Using QbD encourages designing quality into a trial during the planning phase. The identification of Critical to Quality (CtQs) factors and specifically Critical Data and Processes (CD&Ps) is key to such a risk-based monitoring approach. A variable that allows monitoring the evolution of risk regarding the CD&Ps is called a Quality Tolerance Limit (QTL) parameter. These parameters are linked to the scientific question(s) of a trial and may identify the issues that can jeopardize the integrity of trial endpoints...

BACKGROUND: Analytical quality by design (AQbD) affords a systematic scaffolding to triumph a continuously validated, robust assay as well as life cycle management. The resuscitative repurposed drug Favipiravir, an oral drug approved for reemerging pandemic influenza in Japan - 2014 used for the treatment of life threatening pathogens such as Ebola, Lassa virus and currently COVID-19. Favipiravir is gaining a great deal of medical importance due to its pharmaceutical applications. OBJECTIVE: To develop and validate a risk based stability indicating RP HPLC method employing AQbD approach using Central Composite Design (Design Expert Software 13...

The current research aims to develop a carrier system for the delivery of a matrix metalloproteinase (MMP) inhibitor along with a bioceramic agent to the periodontal pocket. It is proposed that the present system, if given along with a systemic antibiotic, would be a fruitful approach for periodontitis amelioration. To fulfill the aforementioned objective, a doxycycline hyclate- and hydroxyapatite-adsorbed composite was prepared by a physical adsorption method and successfully loaded inside sodium alginate-chitosan nanoparticles and optimized based on particle size and drug content...

Nanosized drug crystals have been reported with enhanced apparent solubility, bioavailability, and therapeutic efficacy compared to microcrystal materials, which are not suitable for parenteral administration. However, nanocrystal design and development by bottom-up approaches are challenging, especially considering the non-standardized process parameters in the injection step. This work aims to present a systematic step-by-step approach through Quality-by-Design (QbD) and Design of Experiments (DoE) for synthesizing drug nanocrystals by a semi-automated nanoprecipitation method...

Aceclofenac (ACE) is a drug that was precisely devised to circumvent the shortcomings associated with diclofenac. However, ACE too corresponds to nonsteroidal anti-inflammatory drug (NSAID)-related adverse effects, but with a lower amplitude. The present investigation seeks to develop liposomes loaded with ACE adopting a central composite design (CCD) and formulate a chitosan-based hydrogel for synergistic anti-inflammatory efficacy and improved ACE dermal administration. On the basis of preliminary vesicle size, Poly Dispersity Index (PDI), and drug entrapment, the composition of lipid, cholesterol, and vitamin E TPGS were chosen as independent variables...

Real-time in-line broad protein content monitoring in biomanufacturing downstream unit operations enables the ability to optimize and afford consistent protein recovery. Protein determination from 2 to 400 mg/mL is demonstrated herein via real-time dual-wavelength LED photometric sensor configured at 280 and 310 nm. The figures of merit of this approach include measurement accuracy within the common acceptance criteria of 100 % ± 5 with negligible bias across the linear dynamic ranges...

Electrospinning has become a widely used and efficient method for manufacturing nanofibers from diverse polymers. This study introduces an advanced electrospinning technique, Xspin - a multi-functional 3D printing platform coupled with electrospinning system, integrating a customised 3D printhead, MaGIC - Multi-channeled and Guided Inner Controlling printheads. The Xspin system represents a cutting-edge fusion of electrospinning and 3D printing technologies within the realm of pharmaceutical sciences and biomaterials...

Polycystic ovarian syndrome (PCOS) is a multi-factorial endocrine disorder affecting women of reproductive age. However, its high prevalence and the unsuccessful translation of conventional modalities have made PCOS a pharmaco-therapeutic challenge. In the present study, we explored bi-formulations (comprising metformin-loaded mucus-penetrating nanoparticles, MTF-MPPs, and myoinositol-loaded mucus-penetrating particles, MI-MPPs) incorporated in a carbomer gel tailored for intravaginal administration. For the development and optimization of the MPPs-gel, a QbD (quality by design) approach was employed, including the initial and final risk assessment, central composite design of experts, and method validation...

A systematic and novel quality by design-enabled, rapid, simple, and economic stability-indicating HPLC method for quantifying nirmatrelvir (NMT) was successfully developed and validated. An analytical target profile (ATP) was established, and critical analytical attributes (CAAs) were allocated to meet the ATP requirements. The method used chromatographic separation using a Purosphere column with a 4.6 mm inner diameter × 250 mm (2.5 μm). The analysis occurred at 50°C with a flow rate of 1...