Biopharmaceutics to optimize formulations

In today's pharmaceutical development pipeline increasing numbers of molecules present sub-optimal pharmacokinetic (PK) data, such as poor exposure, large variability, short half-life, or Cmax-related adverse events (AEs). 

To embark on formulation optimization, it is key to understand the biopharmaceutic properties of the compound, as that will guide the formulation strategy and technology selection. 

Biopharmaceutics examines the relationship between the physicochemical properties of the drug. This includes the dosage form and route of administration on the rate and extent of systemic drug absorption.

To deliver the right amount of drug at the right time, with the correct concentration to achieve a therapeutic effect, our formulators must understand systemic exposure of the drug. 

For an orally-administered drug, examining biopharmaceutics gives us the information we need to adjust formulations so that more of the drug is absorbed, improving its effectiveness.

Quotient Sciences use the DCS to help drive formulation strategies

Poorly soluble molecules are increasingly prevalent in early development, requiring enhanced formulation technologies to achieve therapeutic outcomes. 

The DCS, developed by Dressman and Butler, is a system used to classify the developability potential of compounds based on solubility and permeability. It classifies compounds into four categories: 

• Class I (high solubility, high permeability)
• Class II (low solubility, high permeability)
• Class III (high solubility, low permeability)
• Class IV (low solubility, low permeability)

Most new molecules fall into Class II, which is sub-divided into Class IIa (dissolution limited) and Class IIb (solubility limited):

• For Class IIb compounds, solubility-enhancement strategies such as spray-dried dispersions (SDDs) and lipids may be used
• For Class IIa compounds, formulation strategies to improve exposure focus on particle size reduction, such as nanomillling and micronization

We can either take your existing data and assign a DCS classification or measure solubility and calculate a predicted human effective permeability (Peff) using GastroPlus® ADMET predictor, performed by our modeling and simulation team based on the compound structure.

Understanding the biopharmaceutic properties of your compound, we can identify a formulation strategy that overcomes the challenges of your molecule and increases the potential of meeting a target product profile (TPP). 

During clinical studies, we are able to rapidly select and optimize formulations in real-time based on emerging clinical data. This is made possible through the application of Translational Pharmaceutics®. 

Translational Pharmaceutics® is an innovative approach to drug development that significantly reduces risks, increases the likelihood of clinical success, and delivers substantial time and cost savings for our customers. It has been used by pharma and biotech companies for nearly two decades and more than 500 programs completed.