Application Note

Developing Oral Dosage Forms: An Approach For Faster Path To Market

Source: Catalent

Challenges in Oral Drug Development
Oral solid dosage form is the most preferred route because of ease of administration and patient compliance. With the emphasis on developing treatments for complex diseases, the nature of the molecules in the global pharmaceutical pipeline is changing and formulating an oral dose has become more challenging - currently, 90% of NMEs are poorly water soluble, poorly permeable, or both. Innovations in drug development have provided a wide variety of techniques and tools to address the bioavailability, stability and manufacturability challenges (table 1). Bioavailability enhancing technologies have brought more than 100 drug products to the market (table 2). However, each drug molecule has unique physicochemical and biopharmaceutical properties and scientists have to weigh multiple factors including the drug development cost, development cycles, and amount of API available before identifying a suitable delivery technology. An agnostic and data-driven approach early on enables formulation scientists to screen formulations and find a technology with optimal bioavailability suitable for animal studies and to enable further development of clinical trial materials.

OptiForm® Solution Suite Offers Fast Path to Phase I
Catalent Pharma Solutions, a global leader in development solutions and drug delivery technologies has designed an agnostic and data-driven approach to make your molecule’s path to the clinic fast, flexible and easy in the form of OptiForm® Solution Suite. OptiForm® Solution Suite is an award winning, integrated formulation screening and development service aimed to help developers find the most suitable formulations during early phase and advance the molecule to animal PK study with minimal amount of API, through a multiple steps approach.

The first stage is meant to understand the complexity of the molecule and evaluate its development potential and risks. The new molecule is fully characterized by high throughput screening tools and the physicochemical properties are thoroughly studied. The salt, crystal-form and co-crystal screening is also applied. Complete pre-formulation data is collected for formulation ranking and risk assessment modeling. Using the Solubility Limited Absorbable Dose (SLAD) model at early stage is vital for early formulation screening. It can assist in reaching the necessary drug exposure and the ability to escalate the dose. The molecule is then ranked according to the Developability Classification System (3) (DCS), which is an effective way of differentiating new molecules based on their developability characteristics such as solubility to dose relationship, permeability and stability risks, and processing risks with selected dose form.

Equipped with an understanding of the molecule and its potential risks that may limit drug exposure; the second stage considers more specific formulations and solutions through the parallel screening of several delivery technologies. If the molecule belongs to DCS IIa and is dissolution rate limited, particle size engineering including micronization and comicronization and salt form approaches are examined closely; if the molecule is DCS IIb with intrinsic solubility issues, amorphous dispersion techniques (spray drying and hot melt extrusion) and lipid formulation are considered. Feasibility studies and rapid prototyping of all available technologies are used to check for effects on drug exposure and the potential for dose escalation. Preliminary stability studies are conducted to assess viability of the selected formulations for further development.

The third stage provides animal PK study materials, a risk ranking of formulation approaches, and a recommended path to first-in-human studies to reach exposure and dose escalation. On completion of this integrated formulation screening and development program, the outcome reflects the true potential of the new molecule in terms of developability. Once animal studies are complete, Catalent offers comprehensive dosage form development, GMP manufacturing, and clinical supply for quick entry into Phase I trials.

This agnostic and data-driven approach is essential for selecting suitable formulations and decreasing the risks associated with new molecules at the early phase. Such an approach can optimize the development pathway to bring the molecule to the market faster.