Development of Topical Nanocarriers for Skin Cancer Treatment Using Quality by Design Approach

2019 ◽  
Vol 26 (35) ◽  
pp. 6440-6458 ◽  
Author(s):  
Erzsébet Csányi ◽  
Mónika Bakonyi ◽  
Anita Kovács ◽  
Mária Budai-Szűcs ◽  
Ildikó Csóka ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Topical Treatment ◽  
Quality By Design ◽  
Drug Carrier ◽  
Treatment Options ◽  
Pharmaceutical Formulations ◽  
Quality Attributes ◽  
Formulation Development ◽  
Quality By Design Approach ◽  
Dermal Administration

Background: One of the most compelling medical challenges of this century is the treatment of cancer and among them, skin cancer is the most common type. Thus, current treatments need to be renewed continuously to handle this challenge. Objective: This review presents considerations which can be employed during the development of nanosized formulations dedicated to the topical treatment of skin cancer. We aimed to collect and organize literature data on the treatment options for skin cancer in order to determine the required quality attributes of an effective dermal anticancer formulation. Method: With the consideration of the Quality by Design (QbD) approach related to the development of new pharmaceutical formulations, a cost-saving process ensuring a high-quality product taking into account patient expectations, industrial and regulatory aspects can be achieved. Furthermore, this concept is highly recommended by regulatory agencies. Results: Our work discusses the current therapies, active agents, drug carrier systems, and evaluation methods in connection with the treatment of skin cancer and outlines Critical Quality Attributes which need to be considered during the development of a nanosized dermal anticancer formulation. Conclusion: The first part of this review summarizes the most important topical treatment therapies for skin cancer and highlights the future therapeutic perspectives, focusing on the benefits of nanotechnology and dermal administration. The second part outlines the critical points of nanosized dermal anticancer formulation development in the view of QbD approach. Our research emphasizes the application of QbD method for a rationalized and more effective anticancer formulation development process.

scholarly journals Development and Validation of a Ultra Flow Liquid Chromatography Method for the Assay of Boceprevir Using a Quality-by-Design Approach

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 3023-3032
Author(s):  
Manish Majumder ◽  
Ramesh B ◽  
Minaketan Tripathy
Keyword(s):  
Risk Assessment ◽  
Flow Rate ◽  
Mobile Phase ◽  
Quality By Design ◽  
Quality Attributes ◽  
Assay Method ◽  
Chromatography Method ◽  
Critical Quality Attributes ◽  
Critical Method ◽  
Quality By Design Approach

Quality by design guided. The assay method of Boceprevir is developed in accordance with ICH Q8(R2) guideline with due validation. .In this process, the Target analytical profile (TAP) of the drug was set and critical method parameters (CMP) were investigated by systematic risk assessment experimentation to control critical Quality Attributes (CQA). In this, A Cause Effect Risk Assessment Matrix with Control-Noise-Experiment (CNX) is used for identifying the high-risk variables i.e Percentage of Organic Modifier (% methanol), pH of the Buffer and flow rate of the mobile phase. The surface response methodology was applied to optimize the critical method parameters (CMP) as well as Critical Quality Attributes (CQA) to find out the Design space of the method. The Optimum assay method condition was mobile phase Acetate Buffer (50mM) pH 5.4: Methanol (11:89), Flow rate: 0.9 ml/min, Lambda Max: 207. The separation was achieved in the Eclip Plus C-18 column (250 × 4.6 mm, 5μm) at ambient temperature. The retention time of Boceprevir was found to be 4.2 min. The method evaluation was performed according to the (Q2R1) ICH guideline.

scholarly journals Analytical Quality by Design Approach to Test Method Development and Validation in Drug Substance Manufacturing

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
N. V. V. S. S. Raman ◽  
Useni Reddy Mallu ◽  
Hanimi Reddy Bapatu
Keyword(s):  
Method Development ◽  
Quality By Design ◽  
Process Analytical Technology ◽  
Assessment Method ◽  
Test Method ◽  
Formulation Development ◽  
Analytical Quality ◽  
Synthetic Process ◽  
Analytical Development ◽  
Quality By Design Approach

Pharmaceutical industry has been emerging rapidly for the last decade by focusing on product Quality, Safety, and Efficacy. Pharmaceutical firms increased the number of product development by using scientific tools such as QbD (Quality by Design) and PAT (Process Analytical Technology). ICH guidelines Q8 to Q11 have discussed QbD implementation in API synthetic process and formulation development. ICH Q11 guidelines clearly discussed QbD approach for API synthesis with examples. Generic companies are implementing QbD approach in formulation development and even it is mandatory for USFDA perspective. As of now there is no specific requirements for AQbD (Analytical Quality by Design) and PAT in analytical development from all regulatory agencies. In this review, authors have discussed the implementation of QbD and AQbD simultaneously for API synthetic process and analytical methods development. AQbD key tools are identification of ATP (Analytical Target Profile), CQA (Critical Quality Attributes) with risk assessment, Method Optimization and Development with DoE, MODR (method operable design region), Control Strategy, AQbD Method Validation, and Continuous Method Monitoring (CMM). Simultaneous implementation of QbD activities in synthetic and analytical development will provide the highest quality product by minimizing the risks and even it is very good input for PAT approach.

Quality by Design Approach for Understanding the Critical Quality Attributes of Cyclosporine Ophthalmic Emulsion

2014 ◽  
Vol 11 (3) ◽  
pp. 787-799 ◽  
Author(s):  
Ziyaur Rahman ◽  
Xiaoming Xu ◽  
Usha Katragadda ◽  
Yellela S. R. Krishnaiah ◽  
Lawrence Yu ◽  
...  
Keyword(s):  
Quality By Design ◽  
Quality Attributes ◽  
Design Approach ◽  
Critical Quality Attributes ◽  
Quality By Design Approach

Formulation Development and Characterization of Darunavir and Ritonavir Sustained Release Tablets using Quality by Design Approach

2021 ◽  
Vol 23 (08) ◽  
pp. 906-930
Author(s):  
Dhaval Patel ◽  
◽  
Hitesh Patel ◽  
Hiren Chaudhary ◽  
◽  
...  
Keyword(s):  
Quality By Design ◽  
Plasma Concentrations ◽  
Matrix Tablets ◽  
Tween 20 ◽  
Cytochrome P450 3A ◽  
Formulation Development ◽  
Sodium Phosphate Buffer ◽  
Sustained Release Tablets ◽  
Quality By Design Approach

Darunavir is a nonpeptidic inhibitor of protease and is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes. It is usually coadministered with low-dose ritonavir (Darunavir/r). Ritonavir is an inhibitor of CYP3A isoenzymes and pharmacologically enhances Darunavir which leads to increased plasma concentrations of darunavir and allows for daily lower dose. Here, we have developed combination SR formulation of Darunavir and Ritonavir and evaluated. In vitro drug release of all formulations was carried out in dissolution medium 900ml of pH 3.0, 0.05 M Sodium Phosphate Buffer + 2% Tween 20 for 75 RPM USP II apparatus (paddle). The results shown that, all the formulations of matrix tablets shown the good release of drug from trialed formulations however all formulations were not releasing the drug in enough amount. In matrix tablets F6, the release of drug shows NLT 80%. So, the formulation F6 have been considered as suitable for the SR tablet of Darunavir and Ritonavir. Tablets were also evaluated though Quality by Design (QbD) method.

scholarly journals Zolmitriptan Intranasal Spanlastics for Enhanced Migraine Treatment; Formulation Parameters Optimized via Quality by Design Approach

2021 ◽  
Vol 89 (2) ◽  
pp. 24
Author(s):  
Asmaa Saleh ◽  
Maha Khalifa ◽  
Seham Shawky ◽  
Amjaad Bani-Ali ◽  
Heba Eassa
Keyword(s):  
Particle Size ◽  
Quality By Design ◽  
Drug Carrier ◽  
Design Approach ◽  
Brain Delivery ◽  
Ethanol Injection ◽  
Potential Measurement ◽  
First Pass ◽  
Quality By Design Approach ◽  
Formulation Parameters

Zolmitriptan is a potent second-generation triptan prescribed for migraine attacks. It suffers low bioavailability (40%) after oral administration due to the hepatic first-pass metabolism. Spanlastics are surfactant-based elastic vesicular drug carrier systems. This study aimed to design and optimize intranasal spanlastic formulations as an alternative approach that directly targets brain delivery, enhancing its bioavailability and avoiding the first-pass effect. The quality by design approach was applied to correlate the formulation parameters (Span 60 and Tween 80 concentrations) and critical quality attributes (entrapment efficiency (EE%) and particle size). Spanlastic formulations were designed based on response surface central composite design and prepared via an ethanol injection method. Designed formulations were characterized by EE% and particle size measurements to select the optimized formula (with a combination of small particle size and high EE%). The optimized formula was further subjected to transmission electron microscopy, zeta potential measurement and ex vivo permeation study. The optimized formulation showed a particle size of 117.5 nm and EE% of 45.65%, with a low percentage of error between the observed and predicted values. Seventy percent of zolmitriptan was permeated through the nasal membrane within 30 min, and it completely permeated within 2 h with a significantly higher steady-state flux compared to plain gel. This study introduced a successful and promising intranasal formulation suitable for further brain delivery analysis.

scholarly journals Validated Modernized Assay for Foscarnet in Pharmaceutical Formulations Using Suppressed Ion Chromatography Developed through a Quality by Design Approach

Separations ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 209
Author(s):  
Ngoc Phuoc Dinh ◽  
Adel Shamshir ◽  
Gjani Hulaj ◽  
Tobias Jonsson
Keyword(s):  
Ion Chromatography ◽  
Quality By Design ◽  
Drug Product ◽  
Pharmaceutical Formulations ◽  
The United States ◽  
Intermediate Precision ◽  
Precision Data ◽  
Relative Standard ◽  
Suppressed Conductivity Detection ◽  
Quality By Design Approach

Inspired by the United States Pharmacopoeia (USP) “monograph modernization” initiative, we developed and validated an assay for foscarnet sodium injection solution (“foscavir”), following quality by design (QbD) principles, incorporating design of experiments (DoE) and multivariate data analysis to establish the design space and robust setpoint of the method. The resulting analytical procedure was based on ion chromatography (IC) with suppressed conductivity detection, employing an isocratic carbonate–bicarbonate eluent system. The assay was successfully validated at the robust setpoint conditions, according to the guidelines established by the International Council for Harmonization (ICH). The linear range stretched at least from 5 to 100 mg/L with high repeatability (relative standard deviation, RSD ≤ 0.3%) both at the target concentration (60 mg/L) and at 50% and 150% from this level. Special attention was given to establish a rugged assay that would be easily transferable between laboratories, and the recorded recoveries of 98.2–100.5% for both the formulated drug product and the drug substance during intermediate precision evaluation at different analysis situations indicated that this mission was accomplished. A multivariate assessment of intermediate precision data acquired using an experimental design scheme revealed that the assay was not adversely affected by any of the situation variables, including the use of different liquid chromatography instrument types, regardless of if they were constructed from inert materials or stainless steel that had been passivated, even though such problems have been reported in several previous methods for analysis of foscarnet.

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