Evaluation of focused ultrasound and ozonolysis as sample treatment for direct determination of mercury by FI-CV-AAS. Optimization of parameters by full factorial design

A novel, simple, validated stability indicating HPLC method was developed for determination of Koptrizon and Tinosorb S. Stability indicating power of the method was established by forced degradation study. The chromatographic separation was achieved with Waters X Bridge column, by using mobile phase consisting of a mixture of acetonitrile : tetrahydrofuran : water (38 : 38 : 24, v/v/v). The method fulfilled validation criteria and was shown to be sensitive, with limits of detection (LOD) and quantitation (LOQ) of 0.024 and 0.08 μg for Koptrizon and 0.048 and 0.16 μg for Tinosorb S, respectively. The developed method is validated for parameters like precision, accuracy, linearity, solution stability, specificity, and ruggedness as per ICH norms. Design expert with ANOVA software with linear model was applied and a 23 full factorial design was employed to estimate the model coefficients and also to check the robustness of the method. Results of the two-level full factorial design, 23 with 10 runs including two-centre-point analysis based on the variance analysis (ANOVA), demonstrated that all three factors, as well as the interactions between retention time of Koptrizon, Tinosorb S, and USP plate count for Koptrizon, are statistically significant.

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Development and validation of LC-MS and NMR methods for the qualitative and quantitative determination of carotenoids in food and byproducts

10.12681/eadd/46167 ◽

2019 ◽

Author(s):

Θάλεια Τσιάκα

Keyword(s):

Quantitative Determination ◽

Factorial Design ◽

2D Nmr ◽

Full Factorial Design ◽

Box Behnken Design ◽

Qualitative And Quantitative ◽

Nmr Methods ◽

Development And Validation ◽

Full Factorial

Τα τελευταία χρόνια, οι νέες καταναλωτικές συνήθειες έδωσαν ώθηση στην αγοράφυσικών προϊόντων με ευεργετικές ιδιότητες. Επιπρόσθετα, η αύξηση των φυσικώνπαραπροϊόντων καθιστά ως επιτακτική ανάγκη την αξιοποίησή τους μέσω τηςπαραλαβής βιοδραστικών ενώσεων από αυτά. Στην παρούσα διατριβή, μελετήθηκε ηανάκτηση καροτενοειδών από παραπροϊόντα φυτικής (βερίκοκα) ή ζωϊκής (κεφάλιγαρίδας) προέλευσης και από λιπιδικά τρόφιμα (κρόκος αυγών και σώμα γαρίδας)εφαρμόζοντας μια συνδυαστική αναλυτική προσέγγιση που περιλαμβάνει (α) εκχυλίσειςυψηλών ενεργειών με χρήση συμβατικών και καινοτόμων πράσινων διαλυτών (φυσικοίβαθιά ευτηκτικοί διαλύτες, NADES) και πειραματικού σχεδιασμού (DOΕ) (β)υγροχρωματογραφία συζευγμένη με φασματομετρία μάζας (LC-MS/MS) καιφασματοσκοπία πυρηνικού μαγνητικού συντονισμού (NMR) και (γ) μοντέλωνπολυμεταβλητής στατιστικής ανάλυσης. Πιο συγκεκριμένα, εφαρμόστηκε εκχύλιση μευπερήχους (UAE) και με μικροκύματα (ΜΑΕ) για την παραλάβη καροτενοειδών από ταμελετούμενα υποστρώματα. Οι συνθήκες εκχύλισης βελτιστοποιήθηκαν με δυοδιαφορετικά DOE μοντέλα (23 full factorial design, Box-Behnken design). Η LC-MS/MSποσοτικοποίηση των καροτενοειδών υπέδειξε την καταλληλότερη μεθόδο εκχύλισης γιακάθε υπόστρωμα. Τα φάσματα NMR (1D-, 2D-NMR) ανέδειξαν το μεταβολικόαποτύπωμα των εκχυλισμάτων παραπροϊόντων βερίκοκου συναρτήσει των τεχνικών καισυνθηκών εκχύλισης. Η ταυτοποίηση των συνεκχυλιζόμενων μεταβολιτών υπεύθυνωνγια την ταξινόμηση των εκχυλισμάτων και η αξιολόγηση της επίδραση των συνθηκώνεκχύλισης σε αυτούς πραγματοποιήθηκε μέσω μοντέλων πολυμεταβλητής στατιστικήςανάλυσης (PCA, OPLS-DA). Συνοψίζοντας, η μελλοντική πιλοτική εφαρμογή τηςπαρούσας αναλυτικής μεθοδολογίας μπορεί να οδηγήσει στην μετατροπή τωνπαραπροϊόντων σε προϊόντα υψηλής προστιθέμενης αξίας και στην εμπορικήαξιοποίησή τους σε διάφορους τομείς της βιομηχανίας (τρόφιμα, φάρμακα, καλλυντικά,τροφοφάρμακα)

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Application of 32 Full Factorial Design and Desirability Function for Optimizing The Manufacturing Process for Directly Compressible Multi-Functional Co-Processed Excipient

Current Drug Delivery ◽

10.2174/1567201817666200508094743 ◽

2020 ◽

Vol 17 (6) ◽

pp. 523-539

Author(s):

Jalpa Patel ◽

Dhaval Mori

Keyword(s):

Factorial Design ◽

Spray Drying ◽

Desirability Function ◽

Full Factorial Design ◽

Angle Of Repose ◽

P Value ◽

Independent Variables ◽

Full Factorial ◽

32 Full Factorial Design ◽

Response Variables

Background: Developing a new excipient and obtaining its market approval is an expensive, time-consuming and complex process. Compared to that, the co-processing of already approved excipients has emerged as a more attractive option for bringing better characteristic excipients to the market. The application of the Design of Experiments (DoE) approach for developing co-processed excipient can make the entire process cost-effective and rapid. Objective: The aim of the present investigation was to demonstrate the applicability of the DoE approach, especially 32 full factorial design, to develop a multi-functional co-processed excipient for the direct compression of model drug - cefixime trihydrate using spray drying technique. Methods: The preliminary studies proved the significant effect of atomization pressure (X1) and polymer ratio (microcrystalline cellulose: mannitol - X2) on critical product characteristics, so they were selected as independent variables. The angle of repose, Carr’s index, Hausner’s ratio, tensile strength and Kuno’s constant were selected as response variables. Result: The statistical analysis proved a significant effect of both independent variables on all response variables with a significant p-value < 0.05. The desirability function available in Design Expert 11® software was used to prepare and select the optimized batch. The prepared co-processed excipient had better compressibility than individual excipients and their physical mixture and was able to accommodate more than 40 percent drug without compromising the flow property and compressibility. Conclusion: The present investigation successfully proved the applicability of 32 full factorial design as an effective tool for optimizing the spray drying process to prepare a multi-functional co-processed excipient.

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Formulation of Extended-Release Beads of Lamotrigine Based on Alginate and Cassia fistula Seed Gum by QbD Approach

Current Drug Delivery ◽

10.2174/1567201817666200317124022 ◽

2020 ◽

Vol 17 (5) ◽

pp. 422-437

Author(s):

Dixita Jain ◽

Akshay Sodani ◽

Swapnanil Ray ◽

Pranab Ghosh ◽

Gouranga Nandi

Keyword(s):

Drug Release ◽

Factorial Design ◽

Extended Release ◽

Polymer Concentration ◽

Green Manufacturing ◽

Full Factorial Design ◽

Cassia Fistula ◽

Negative Environmental Impact ◽

Seed Gum ◽

Full Factorial

Aim: This study was focused on the formulation of the multi-unit extended-release peroral delivery device of lamotrigine for better management of epilepsy. Background: The single-unit extended-release peroral preparations often suffer from all-or-none effect. A significant number of multi-unit delivery systems have been reported as a solution to this problem. But most of them are found to be composed of synthetic, semi-synthetic or their combination having physiological toxicity as well as negative environmental impact. Therefore, fabrication and formulation of multi-unit extended-release peroral preparations with natural, non-toxic, biodegradable polymers employing green manufacturing processes are being appreciated worldwide. Objective: Lamotrigine-loaded extended-release multi-unit beads have been fabricated with the incorporation of a natural polysaccharide Cassia fistula seed gum in calcium-cross-linked alginate matrix employing a simple green process and 23 full factorial design. Methods: The total polymer concentration, polymer ratio and [CaCl2] were considered as independent formulation variables with two different levels of each for the experiment-design. The extended-release beads were then prepared by the ionotropic gelation method using calcium chloride as the crosslinkerions provider. The beads were then evaluated for drug encapsulation efficiency and drug release. ANOVA of all the dependent variables such as DEE, cumulative % drug release at 2h, 5h, 12h, rate constant and dissolution similarity factor (f2) was done by 23 full factorial design using Design-Expert software along with numerical optimization of the independent variables in order to meet USP-reference release profile. Results: The optimized batch showed excellent outcomes with DEE of 84.7 ± 2.7 (%), CPR2h of 8.41± 2.96 (%), CPR5h of 36.8± 4.7 (%), CPR12h of 87.3 ± 3.64 (%) and f2 of 65.9. Conclusion: This approach of the development of multi-unit oral devices utilizing natural polysaccharides might be inspiring towards the world-wide effort for green manufacturing of sustained-release drug products by the QbD route.

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