Accelerating Drug Development Timelines with Innovative Formulation Strategies

By Richard Johnson, Chief Scientific Officer, Upperton

In the pharmaceutical industry, targeting and delivering a drug to the correct site and enhancing the bioavailability of drug compounds are two critical challenges that can delay successful development programmes and require different technical capabilities to achieve a successful product. Low bioavailability can lead to reduced efficacy, necessitating higher doses and potentially causing adverse effects. Delivering drugs into the nasal cavity presents different challenges, including the need to develop suitable formulations, device selection and subsequent testing of drug/device combinations. To address these differing challenges, innovative formulation strategies are essential to speed up drug development timelines.

Two platforms developed by Upperton to address these different challenges include UpperSolv and UpperNose.

UpperSolv™: Tackling Poor Solubility

UpperSolv™ is designed to address the challenges associated with poorly soluble drugs, which often exhibit low bioavailability. The platform employs a rapid, data-driven formulation strategy to identify the most suitable approach for enhancing solubility and, consequently, bioavailability. This strategy not only optimises therapeutic efficacy but also streamlines the development process, saving both time and resources.

UpperSolv™ offers several key features that enhance drug formulation efficiency. The platform requires as little as 5 grams of the active pharmaceutical ingredient (API) to evaluate up to six different formulations, reducing material costs and enabling early-stage development even with limited API availability. It also ensures a rapid turnaround, with the entire study, including pharmacokinetic (PK) data generation, typically completed within eight weeks.

This accelerates decision-making and helps advance formulations quickly. UpperSolv™ employs an adaptive approach, tailoring its methodology based on the specific characteristics of the molecule and the client’s objectives to optimize formulation strategies. Additionally, it integrates formulation and biopharmaceutical assessments to select the most appropriate strategy, providing a comprehensive understanding of the formulation’s performance and increasing the likelihood of clinical success.

UpperSolv™ Process Overview:

• Solubility Screening: The API is dissolved using a range of solvents, co-solvents, and solubilizing excipients to determine its solubility profile.

• Application of Enabling Technologies: Formulated intermediates or prototype products are developed using techniques such as lipid-based formulations, amorphous formulations via co-milling, and amorphous solid dispersions created by spray drying.

• In Vitro Characterization and Stability Testing: The prototypes undergo rigorous testing to assess their performance and stability under various conditions.

• Comparative Pharmacokinetic Assessment: Selected formulations are evaluated in small animal models to gather PK data, informing decisions on the most promising formulation strategy.

Implementing the UpperSolv™ platform and approach helps to make informed, data-driven decisions early in the development process, reducing the risk of late-stage failures and accelerating the timeline to clinical trials.

UpperNose™: Enhancing Nasal Drug Delivery

UpperNose™ focuses on the development of nasal drug delivery systems, an alternative route of administration that can offer an alternative delivery route for injectable or orally administered drugs

Nasal drug delivery offers several advantages that make it an effective alternative to these traditional administration routes. The nasal mucosa provides a rich vascular network, allowing for rapid absorption into the systemic circulation, which is especially beneficial for drugs requiring a fast onset of action and drugs that are usually administered via an injection.

It is also a non-invasive method, offering a patient-friendly alternative to injections, which can improve compliance and ease of use. Additionally, nasal delivery bypasses first-pass metabolism, avoiding degradation by liver enzymes and enhancing bioavailability for certain drugs, making it a valuable option for improving drug efficacy and patient outcomes.

UpperNose™ Capabilities:

• Formulation Development: Expertise in creating both liquid and dry powder nasal formulations, tailored to the physicochemical properties of the API.

• Particle Engineering: Utilizes advanced techniques to optimize particle size and morphology, ensuring efficient deposition in the nasal cavity.

• Device Selection: Collaborates with device manufacturers to select and test appropriate delivery devices, ensuring compatibility and optimal performance.

By leveraging the UpperNose™ platform, Upperton Pharma Solutions provides a comprehensive approach to nasal drug delivery, addressing formulation challenges and facilitating the development of effective nasal therapeutics.

Impact on Drug Development Timelines

The integration of UpperSolv™ and UpperNose™ into the drug development process offers significant advantages for clients in terms of efficiency and speed.

UpperSolv™ enables rapid identification of viable formulation strategies, allowing for quicker progression to preclinical studies. The streamlined process reduces the time required to optimize formulations, which is crucial in the early stages of drug development.

With robust data from UpperSolv™ studies, companies can confidently move into Phase I clinical trials with formulations that have demonstrated improved bioavailability. This reduces the likelihood of unexpected issues arising during clinical development, thereby shortening timelines and conserving resources.

UpperNose™ facilitates the development of nasal delivery systems that offer rapid onset of action and improved patient compliance. This established development platform enables customers to rapidly transition their molecule into the nasal drug delivery arena, using tried and tested formulation and device combinations and the latest analytical methods to ensure rapid development and progression into the clinic.