There is somewhat of a consensus in life sciences that there have been significant advancements in improving bioavailability. Solubility, however, continues to elude formulators. Excipients are often lauded as a solution to tackling these challenges, but still do fall short. In a 2020 US Pharmacopeia (USP) survey of drug formulators, 84% said that the current roster of excipients present in approved drug products has imposed limitations on drug development, and as many as 28% experienced a discontinuation of drug development as a result of excipient limitations.

Novel excipients may be the answer. In September 2023, the Office of New Drugs and the Center for Drug Evaluation and Research (CDER) launched a voluntary Pilot Program for the Review of Innovation and Modernization of Excipients (PRIME). This program is intended to allow biopharmaceutical manufacturers to obtain FDA review of novel excipients. The development of novel excipients is gaining momentum as pharmaceutical companies seek improved performance and versatility in drug formulations. Novel substances support nanoparticle drug delivery for oncological medications to provide better stability and adoption of medicines.

“The invention of novel excipients bearing the amphiphilic and solubilization characteristics in the recent past has helped excipient and drug manufacturers alike to overcome the regulatory barriers for expediting the new drug candidates to market,” says Shaukat Ali, PhD, Senior Director of Scientific Affairs and Technical Marketing at Ascendia Pharmaceutical Solutions.

According to a May 2024 USP white paper: “While the FDA PRIME program represents a step in a new regulatory direction for excipients, drug developers are currently reluctant to use novel excipients as there is no independent FDA regulatory pathway outside of its drug application and approval process to review and evaluate the safety and toxicity of an excipient for introduction into a new drug, abbreviated new drug, or non-prescription drug. FDA may determine that novel excipients are not fully supported by the submitted safety data such as for the proposed level of exposure, route of administration, duration of exposure, and patient population. An entire drug application using a novel excipient could be rejected due to uncertainty surrounding acceptance of the excipient by FDA. Considering the barriers to using novel excipients that exist in the normal application process for drug products, USP supports the development of a transparent, independent approval pathway for novel excipients.”

This exclusive Drug Development & Delivery annual report explores the use of novel excipients as well as other methods and technologies for tackling bioavailability and solubility once and for all.

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Hovione: Early-Stage ASDs by Spray Drying Result in Viable Oral Dosage Form

Amorphous solids dispersions (ASDs) remain the most used enabling platform for solubility enhancement. There are a variety of molecule structures in the pipeline that require tailored bioenhance­ment, including the common greaseballs as well as chameleonic and brick-dust APIs. “ASDs by spray drying are a versatile platform to formulate across the board,” says Inês Ramos, R&D Manager (Formula­tion Development, Oral Drug Product) at Hovione.

For BCS II and IV compounds, bioavailability enhancement is driven by absorption enhancement needs, target product profile, and drug molecular fea­tures. “To maintain a strong focus on man­ufacturability since early-stage, the delivery of a viable ASD oral dosage form follows an integrated approach involving ASD for­mulation screening, particle engineering, drug product formulation and process de­velopment using data-driven tools to ex­pedite development,” says Dr. Ramos.

Hovione’s approach relies on a streamlined workflow supported by com­putational tools that starts with a “technol­ogy fitting” to assess the suitability of using ASDs by spray drying. ASD development includes a comprehensive high-through­put formulation screening (ASD-HIPROS™ proprietary platform that includes com­mon polymers and alternative excipients such as the Dispersome® technology), de­signed to fast-track first-in-human (FiH) formulations that are scalable and provide adequate performance. The ASD-HIPROS platform requires a few grams of API and less than eight weeks to narrow down thousands of possible formulations to the most viable candidates. The drug product intermediate is then formulated into a tablet, capsule, or pellets/granules for oral delivery. “This methodology was designed to expedite the delivery of an enabling for­mulation and an industrially viable manu­facturing process,” says Dr. Ramos. “The goal is to maintain performance and en­sure patience compliance.”

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