A Review on Various Analytical Methodologies for Etoricoxib

Etoricoxib belongs to the class of highly selective COX-2 inhibitor NSAIDs. It is mostly used for the treatment of pain, arthritic conditions including rheumatoid arthritis and osteoarthritis. The current study focuses primarily on analytical and bioanalytical method development methodologies, as well as numerous methods established for the estimation of etoricoxib, whether in pharmaceutical dose form or in bulk. Analytical procedures are critical for determining compositions, as they allow us to obtain both qualitative and quantitative results utilising advanced analytical tools. The analytical method for Etoricoxib may be chromatographic, electrochemical, spectral or hyphenated. These methods aid in the comprehension of critical process parameters as well as the minimization of their impact on precision and accuracy. Analytical method development is required to sustain high commercial product quality standards and to meet regulatory requirements. Following the reference, regulatory organisations in several nations have established standards and procedures for providing approval, authentication, and registration. Bioanalytical methods are designed to quantify the concentration of drug, metabolite, or typical biomarkers from various biological fluids including serum, urine, saliva and tissue extracts.

A Data-Driven Framework to Predict Fused Filament Fabrication Part Properties Using Surrogate Models and Multi-Objective Optimisation

In additive manufacturing (AM), due to large number of process parameters and multiple responses of interest, it is hard for AM designers to attain optimal part performance without a systematic approach. In this research, a data-driven framework is proposed to achieve the desired AM part performance and quality by predicting part properties and optimizing AM process parameters effectively and efficiently. The proposed framework encompasses efficient sampling of design space and establishing the initial experiment points. Based on established empirical data, surrogate models, are used to characterise influence of critical process parameters on responses on interest. Further, process maps can be generated for enhancing understanding on the influence of process parameters on responses of interests and AM process characteristics. Subsequently, multi-objective optimisation coupled with a multi criteria decision making technique is applied to determine an optimal design point, which maximises the identified responses of interest to meet the part functional requirements. A case study is used to validate the proposed framework for optimising an ULTEM™ 9085 fused filament fabrication part to meet its functional requirements of surface roughness and mechanical strength. From the case study, results indicate that the proposed approach is able to achieve good predictive results for responses of interest with a relatively small dataset. Further, process maps generated from the surrogate model provide a visual representation of the influence between responses of interest and critical process parameters for FFF process, which traditionally requires multiple investigations to arrive at similar conclusions.

PRELIMINARY STUDY OF INSULIN DRY POWDER FORMULATION: CRITICAL PROCESS PARAMETERS ON SPRAY-FREEZE-DRYING AND CRITICAL MATERIAL ATTRIBUTE OF TREHALOSE AND INULIN AS STABILIZER

Objective: The aim of this study was to obtain recommendations about critical process parameters (CPP) and optimal ratio of trehalose and inulin as critical material attribute (CMA) on insulin dry powder formulation with spray-freeze-drying (SFD) method. Methods: Inulin dry powder was formulated with the SFD method, which consisted of an atomization process and freeze-drying (FD). SFD processes were optimized in order to obtain dry powder and CPP was analyzed. All seven variations of formulas proceeded with physicochemical characterization to obtain the optimal formula. Results: In the early optimization, there was a slight time lag between the atomization process and FD; as a result, some of the powder coagulated and crystallized. Another critical parameter was that the FD process should not be interrupted for at least 50 h of FD. Dry powder proceeded with physicochemical characterization, a formula without inulin showed semicrystalline properties, while six formulas had amorphous properties due to its combination. All formulas had a spherulite shape and rough surface. Five formulas with the combination of trehalose and inulin obtained dry powders with a diameter range of 30-43 μm, moisture content below 3.5% and high encapsulation efficiency (EE). Formula with the ratio of 1:1 (F4) showed optimal properties with moisture content and EE of 2.62% and 99.68%, respectively. Conclusion: This study concluded that there were two critical process parameters in the SFD method. There should be no time lag in SFD process and FD time which should not be interrupted. The optimal ratio for trehalose and inulin was shown by F4 with ratio of 1:1.

Gene Therapy: Development, Design of Studies, and Approval Process

Genome editing can be applied to various areas of medical diagnosis and treatments. Gene therapy pre-market applications comprise of systematically assessing a product’s design controls, manufacturing process controls, and proposed protocols for post-marketing surveillance. Quality risk management principles have been described in various FDA regulatory guidances for several aspects of good manufacturing practices (GMPs) such as several stages of process validation and verification in the genome product’s life cycle including critical quality attributes (CQAs) and monitoring critical process parameters (CPPs). A CPP is defined as a process parameter whose variability has an impact on a CQA of genome product and, therefore, should be monitored or controlled to ensure that the manufacturing process produces an end product of the desired quality. FDA’s mission is to facilitate the premarket review and evaluation of new genomic products for clinical use. The FDA guidances emphasize a quality management approach to the design of studies by providing oversight and objective review based on risk-benefit analysis of new genomic products. FDA reviews, evaluates, verifies and validates the implementation of the regulatory design-control requirements which are applied to the control genomic product’s quality throughout the total product life cycle (TPLC) [1-5].

Optimization of Spiral-Wound Microfiltration Process Parameters for the Production of Micellar Casein Concentrate

A systematic selection of different transmembrane pressures (TMP) and levels of diafiltration (DF) was studied to optimize these critical process parameters during the manufacturing of micellar casein concentrate (MCC) using spiral-wound polymeric membrane filtration. Three TMPs (34.5, 62.1, and 103.4 kPa) and four DF levels (0, 70, 100, and 150%) were applied in the study. The effect of the TMP and DF level on flux rates, serum protein (SP) removal, the casein-to-total-protein ratio, the casein-to-true-protein ratio, and the rejection of casein and SP were evaluated. At all transmembrane pressures, the overall flux increased with increases in the DF level. The impact of DF on the overall flux was more pronounced at lower pressures than at higher pressures. With controlled DF, the instantaneous flux was maintained within 80% of the initial flux for the entire process run. The combination of 34.5 kPa and a DF level of 150% resulted in 81.45% SP removal, and a casein-to-true-protein ratio of 0.96. SP removal data from the lab-scale experiments were fitted into a mathematical model using DF levels and the square of TMPs as factors. The model developed in this study could predict SP removal within 90–95% of actual SP removal achieved from the pilot plant experiments.

An Updated Risk Assessment as Part of the QbD-Based Liposome Design and Development

Liposomal formulation development is a challenging process. Certain factors have a critical influence on the characteristics of the liposomes, and even the relevant properties can vary based on the predefined interests of the research. In this paper, a Quality by Design-guided and Risk Assessment (RA)-based study was performed to determine the Critical Material Attributes and the Critical Process Parameters of an “intermediate” active pharmaceutical ingredient-free liposome formulation prepared via the thin-film hydration method, collect the Critical Quality Attributes of the future carrier system and show the process of narrowing a general initial RA for a specific case. The theoretical liposome design was proved through experimental models. The investigated critical factors covered the working temperature, the ratio between the wall-forming agents (phosphatidylcholine and cholesterol), the PEGylated phospholipid content (DPPE-PEG2000), the type of the hydration media (saline or phosphate-buffered saline solutions) and the cryoprotectants (glucose, sorbitol or trehalose). The characterisation results (size, surface charge, thermodynamic behaviours, formed structure and bonds) of the prepared liposomes supported the outcomes of the updated RA. The findings can be used as a basis for a particular study with specified circumstances.