Dose Justification for Nanoparticle Formulation | Chapter 2 | Pharmaceutical Science: New Insights and Developments Vol. 8

 

Dose justification refers to the scientific rationale behind selecting a specific dose of a drug for human use. With the emergence of nanotechnology in pharmaceuticals, particularly nanoparticle formulations, this concept has evolved significantly. This study aims to shed light on the different approaches to justifying the dose of nanoparticles, using ibrutinib nanoparticles as an example. It also examines the relation between the dose and bioavailability, alongside considering relevant pharmacokinetic (PK) and pharmacodynamic (PD) parameters. The biopharmaceutical factors like Cmax, Tmax, and AUC are also considered for dose justification. The comparison of the radiation dose and nanoparticle dose taken internally or externally, and their relation, is highlighted. The NOAEL (No Observed Adverse Effect Level) and its limitations are discussed. The human equivalent dose and inhumane studies were listed along with the equivalent dose of nanoparticles. The Equivalent Dose Model, used in nanotoxicology, is presented as it calculates dose based on nanoparticle surface area rather than mass alone. Comprehensive data support the approval of the 50 mg nanoparticle dose, providing patients with a more effective and safer treatment option. Project Optimus by the FDA, which aims to refine and simplify oncology dose selection, is also considered. Key nanoparticle-specific factors like surface area and zeta potential are explained with the regulatory approvals. Nano drug formulations offer significant improvements in solubility and bioavailability. Incorporating PK/PD data, toxicity thresholds, nanoparticle-specific models, and regulatory guidelines ensures that the new dose maintains safety and efficacy. Finally, the integration of in silico modelling, Quantitative Structure-Activity Relationship model, and machine learning is proposed to enhance dose predictions, with standardised weighting factors suggested to improve risk assessment.

 

Author(s) Details

AVS Rajeswari
Department of Pharmaceutics, Arya College of Pharmacy, Kandi, Hyderabad, India.

 

B. Navya
Arya College of Pharmacy, Kandi, Hyderabad, India.

 

N. Sowmya
Arya College of Pharmacy, Kandi, Hyderabad, India.

 

P. Sailaja
Andhra University College of Pharmaceutical Sciences, Visakhapatnam, AP, India.

 

Please see the book here:- https://doi.org/10.9734/bpi/psnid/v8/6145