Examining the Impact of Excipient Material Property Variation on Drug Product Quality Attributes: A Quality-By-Design Study for a Roller Compacted, Immediate Release Tablet

2011 ◽  
Vol 100 (6) ◽  
pp. 2222-2239 ◽  
Author(s):  
Joseph Kushner ◽  
Beth A. Langdon ◽  
Jon I. Hiller ◽  
Glenn T. Carlson
Keyword(s):  
Product Quality ◽  
Material Property ◽  
Quality By Design ◽  
Drug Product ◽  
Immediate Release ◽  
Quality Attributes ◽  
Design Study ◽  
Property Variation ◽  
The Impact ◽  
Release Tablet

scholarly journals Application of the Gastrointestinal Simulator (GIS) Coupled with In Silico Modeling to Measure the Impact of Coca-Cola® on the Luminal and Systemic Behavior of Loratadine (BCS Class 2b)

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 566 ◽  
Author(s):  
Bart Hens ◽  
Marival Bermejo ◽  
Patrick Augustijns ◽  
Rodrigo Cristofoletti ◽  
Gregory Amidon ◽  
...  
Keyword(s):  
Intestinal Absorption ◽  
Buffer Capacity ◽  
Drug Product ◽  
Tap Water ◽  
Systemic Exposure ◽  
Immediate Release ◽  
Release Formulation ◽  
Gastric Emptying Rate ◽  
Physiological Variables ◽  
The Impact

In the present work, we explored if Coca-Cola® had a beneficial impact on the systemic outcome of the weakly basic drug loratadine (Wal-itin®, immediate-release formulation, 10 mg, generic drug product). To map the contribution of underlying physiological variables that may positively impact the intestinal absorption of loratadine, a multi-compartmental and dynamic dissolution device was built, namely the Gastrointestinal Simulator (GIS). The luminal behavior of one immediate-release (IR) tablet of 10 mg of loratadine was tested under four different fasted state test conditions in the GIS: (i) with 250 mL of water and applying a predetermined gastric half-life (t1/2,G) of 15 min; (ii) with 250 mL of water and applying a t1/2,G of 30 min; (iii) with 250 mL of Coca-Cola® and a t1/2,G of 15 min; (iv) with 250 mL of Coca-Cola® and a t1/2,G of 30 min. After initiating the experiments, solution concentrations and solubility were measured in the withdrawn samples, and pH was monitored. To address the impact of the present CO2 in Coca-Cola® on the disintegration time of the tablet, additional disintegration experiments were performed in a single-vessel applying tap water and sparkling water as dissolution media. These experiments demonstrated the faster disintegration of the tablet in the presence of sparkling water, as the present CO2 facilitates the release of the drug. The buffer capacity of Coca-Cola® in the presence of FaSSGF was 4-fold higher than the buffer capacity of tap water in the presence of FaSSGF. After performing the in vitro experiments, the obtained results were used as input for a two-compartmental pharmacokinetic (PK) modeling approach to predict the systemic concentrations. These simulations pointed out that (i) the present CO2 in Coca-Cola® is responsible for the enhancement in drug release and dissolution and that (ii) a delay in gastric emptying rate will sustain the supersaturated concentrations of loratadine in the intestinal regions of the GI tract, resulting in an enhanced driving force for intestinal absorption. Therefore, co-administration of loratadine with Coca-Cola® will highly likely result in an increased systemic exposure compared to co-administration of loratadine with tap water. The mechanistic insights that were obtained from this work will serve as a scientific basis to evaluate the impact of Coca-Cola® on the systemic exposure of weakly basic drugs for patients on acid-reducing agents in future work.

scholarly journals Optimized chronomodulated dual release bilayer tablets of fexofenadine and montelukast: quality by design, development, and in vitro evaluation

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Bhupendra Singh ◽  
Geetanjali Saini ◽  
Manish Vyas ◽  
Surajpal Verma ◽  
Sourav Thakur
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Quality By Design ◽  
Immediate Release ◽  
Oral Dosage ◽  
Nocturnal Asthma ◽  
Sustained Release Tablet ◽  
Bilayer Tablets ◽  
Dual Release ◽  
Release Tablet

Abstract Background The conventional oral dosage forms are not effective in dealing with chronopathological conditions, such as nocturnal asthma. Therefore, there is an unmet need to develop a delivery system that can deliver drug as per the chronopharmacology of the diseases. The purpose of the study is to use quality by design (QbD) technique and pulsatile principles for the development of Eudragit-coated dual release bilayer tablets. The dual layer consists of immediate release layer of fexofenadine HCl and sustained release layer of montelukast sodium. Results The quality target product profile of the formulation was developed, and the critical quality attributes were identified. Three-level, three-factor Box-Behnken design was used for the optimization of the bilayer tablets. Based on the design, a total of 13 formulation combinations (F1–F13 and M1–M13) were made having acceptable micromeritic properties. The developed immediate and sustained release layers were evaluated for physicochemical properties. Depending upon the value of the diffusion exponent, the Fickian diffusion mechanism is dominant among immediate and sustained release tablet layers. Response curve for immediate release layer showed that concentrations of sodium starch glycolate and sodium bicarbonate had a negative effect on disintegration time and a positive effect on drug release. For sustained release tablet layer, concentrations of HPMC E 5 LV and magnesium stearate had a significant effect on drug release. The ANOVA and diagnostic plots confirmed the significance and goodness of fit of the used model. Based on desirability plot values, optimized formulation was developed and coated with Eudragit coat. The coated bilayer tablet showed met the requirement of providing an immediate release during the first hour and a sustained release action for a period of more than 8 h after passing the gastric region. Conclusions The formulation can be fruitful in curbing the menace of nocturnal asthma and providing a high degree of patient compliance as the patient will not have to wake up at night to take the medication.

Quality by Design in Pharmaceutical Formulation

2019 ◽  
pp. 221-239
Author(s):  
Sundaramurthy Vivekanandan
Keyword(s):  
Quality By Design ◽  
Drug Product ◽  
Quality Attributes ◽  
Pharmaceutical Products ◽  
Design Approach ◽  
Critical Quality Attributes ◽  
Quality Product ◽  
Product Profile ◽  
Critical Material Attributes ◽  
Quality By Design Approach

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.

scholarly journals QUALITY BY DESIGN APPROACH: REGULATORY NEED, CURRENT, AND FUTURE PERSPECTIVE

2021 ◽  
pp. 29-35
Author(s):  
AAYUSHI RAJORA ◽  
GURMEET CHHABRA
Keyword(s):  
Quality By Design ◽  
Raw Materials ◽  
Drug Product ◽  
Active Pharmaceutical Ingredient ◽  
Pharmaceutical Products ◽  
Future Perspective ◽  
Development Methodology ◽  
Unit Of Measurement ◽  
The Impact ◽  
Analytical Technology

Quality by design (QbD) is utilized in the event of pharmaceutical processes to create certain predefined product quality. QbD ideas unit of measurement explained in International Conference on Harmonization (ICH) pointers Q8 (R1) (Pharmaceutical development), Q9 (Quality risk management [QRM]), and Q10 (Pharmaceutical quality system). ICH Q8 (R1) guideline defines QbD as “a systematic approach to develop that begins with predefined objectives and emphasizes product and methodology, understanding, and methodology management, supported sound science and QRM.” QbD approach studied the implications of various input variables (e.g. methodology parameters, and materials) of the merchandise development methodology, on the final word product (active pharmaceutical ingredient or drug product). The late QbD approach integrates the principles of QRM, and methodology analytical technology (PAT). QbD combined with methodology analytical technology (PAT) tools modify methodology management and increase assurance that the merchandise quality attributes unit of measurement achieved consistently. An integrated and risk-based approach for review of the merchandise development methodology is also a future need of the QbD plan. Although implementing the QbD approach is not a restrictive demand, restrictive agencies to supply flexibility in their pointers for producing that unit of measurement developed by the QbD approach. Rising trends embody the growing interest in quantifying and managing the impact of raw materials’ attributes variability of methodology and product, what is more, as a result of the event of retrospective QbD approaches in complement to simple QbD. Thus, the QbD approach is also a tool for developing worth effective and quality pharmaceutical products.

Sign in / Sign up

Export Citation Format

Share Document