Optimization of wet granulation process for manufacturing Rivaroxban generic immediate-release tablets using PBPK
Jailani Shiekmydeen1,2, Tanisha3, Sonam Sharma3
1Department of Pharmacy, Faculty of Engineering and Technology (FEAT), Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu India.
In Silico Pharmacology
|August 26, 2024
Summary
Optimizing the wet granulation process for rivaroxaban (RXB) tablets using PBPK modeling is crucial for generic drug development. This approach ensures successful bioequivalence for poorly soluble drugs, overcoming formulation challenges.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery
- Pharmacokinetics
Background:
- Granulation is key for poorly water-soluble drugs, impacting dissolution and bioequivalence.
- Rivaroxaban (RXB), a 20 mg high-strength drug, exhibits 66% fasting bioavailability and poses formulation challenges.
- Failed bioequivalence in previous batches highlights issues with improper granulation.
Purpose of the Study:
- To optimize the wet granulation process for manufacturing rivaroxaban (RXB) generic immediate-release tablets.
- To demonstrate the utility of physiologically based pharmacokinetic (PBPK) modeling in process optimization.
- To ensure successful bioequivalence for high-strength generic drug products.
Main Methods:
- Physiologically based pharmacokinetic (PBPK) modeling and simulations were employed.
- The study focused on optimizing the wet granulation process parameters.
- Virtual bioequivalence assessments were conducted.
Main Results:
- PBPK modeling provided insights into optimizing the wet granulation process for RXB tablets.
- Optimized granulation is essential for achieving desired dissolution profiles and bioequivalence.
- The study successfully identified a path for developing generic RXB tablets.
Conclusions:
- PBPK modeling is a valuable tool for both formulation and process optimization in pharmaceutical development.
- Successful optimization of the wet granulation process is critical for rivaroxaban generic product development.
- This study aids in overcoming bioequivalence challenges for high-strength, poorly soluble drugs.
Related Concept Videos
01:28Factors Influencing Drug Absorption: Pharmaceutical Parameters
123
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
123
01:19One-Compartment Open Model for IV Bolus Administration: General Considerations
173
The one-compartment model is a pharmacokinetic tool that models the body as a single, uniform compartment, facilitating the understanding of drug distribution and elimination. This model is particularly beneficial for intravenous (IV) bolus administration, where the drug rapidly circulates throughout the body.
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...
173
01:09One-Compartment Open Model for IV Bolus Administration: Estimation of Elimination Rate Constant, Half-Life and Volume of Distribution
228
The one-compartment open model is a simplified approach used in pharmacokinetics to understand the distribution and elimination of a drug administered through an intravenous bolus. This model assumes rapid drug dispersal throughout the body and elimination using a first-order process. Key pharmacokinetic parameters, such as the elimination rate constant (k), half-life (t1/2), and the apparent volume of distribution (Vd), can be estimated from this model. The elimination rate is calculated...
228
01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
34
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
34
01:23Factors Affecting Dissolution: Particle Size and Effective Surface Area
766
Dissolution kinetics, an essential aspect of oral drug delivery, is significantly influenced by the drug's particle size. According to the Noyes-Whitney dissolution model, the dissolution rate correlates directly with the drug's surface area. The larger the surface area, the higher the drug's solubility in water, leading to a faster drug dissolution rate. Reducing particle size increases the effective surface area, enhancing the dissolution process. Micronization and nanosizing are...
766
01:18Two-Compartment Open Model: IV Bolus Administration
429
The two-compartment model for intravenous (IV) bolus administration illustrates drug distribution in the body, subdividing it into central and peripheral compartments. This model operates on the concept of two-compartment kinetics. The drug's plasma concentration shows a bi-exponential decline following IV bolus administration, signaling the presence of two disposition processes: distribution and elimination.
The disparity between drug input and the sum of drug transfer rates between...
The disparity between drug input and the sum of drug transfer rates between...
429