The development of enhanced drug formulations requires an in-depth, data-driven understanding of Active Pharmaceutical Ingredients’ (APIs) physicochemical properties and their behavior in vivo. At BioDuro, formulation challenges such as poor solubility, stability, and bioavailability are addressed by systematically analyzing key characteristics of the API and the target patient population, explains Dr. Yuan Yang, Senior Scientist III, Formulation Development, BioDuro. A scientific approach that balances the inherent risk of formulation complexity with the practical needs of the drug product is critical for success.
For APIs with poor solubility, several formulation strategies are employed, each with specific advantages and challenges depending on the solubility profile and therapeutic window. Nanoparticles, nanocrystals, lipid-based formulations, cyclodextrin incorporation, and Amorphous Solid Dispersions (ASD) have proven to be essential tools for solubility enhancement. “BioDuro specializes in employing these strategies, selecting the most suitable formulation based on factors such as API stability, solubility, partition coefficient, and the required dose strength,” he says.
By transforming the API into an amorphous state and dispersing it in a polymer matrix, ASDs improve dissolution rates while maintaining stability. This strategy is particularly beneficial for drugs with poor solubility, as it enhances dissolution rates and improves the drug’s absorption, leading to more consistent and predictable bioavailability. By leveraging precise modeling and predictive tools, formulation scientists can mitigate risks while maximizing therapeutic performance.
The core of formulation enhancement often lies in the ability to manipulate the physical form of the API. Spray drying and hot melt extrusion (HME) are widely used, proven techniques that provide effective solutions for API solubility challenges. Conventional spray drying has been the standard for producing amorphous dispersions and enhancing the bioavailability of poorly soluble drugs. Dr. Yang says: “With a success rate of over 90% in scale-up from lab to commercial manufacturing, spray drying is a reliable method for formulating high-quality solid dispersions.” HME, similarly, is recognized for its capacity to produce stable, uniform formulations and is integral to the development of immediate-release and controlled-release dosage forms, with more than 50% of commercial products utilizing this technique. However, the increasing complexity of drug candidates has led to the exploration of newer technologies to address evolving challenges. “Electrospray, a cutting-edge technique, has gained significant attention in producing ASDs,” he says. “Electrospray offers several advantages, such as highly repeatable and reproducible processes and the ability to produce fine, uniform particles with a narrow size distribution. Studies show that electrospray-generated formulations exhibit improved stability and dissolution rates compared to conventional methods, making them particularly beneficial for high-potency, low-dose drugs.”
In addition to electrospray, other emerging technologies are being explored to enhance solubility and bioavailability. Techniques, such as formulating with solubility-enhancing excipient, amorphous dispersion granulation and coating fluid bed, co-precipitation, and electrospinning are being evaluated for their potential to improve the solubility of challenging APIs. These approaches, alongside spray drying, HME, and electrospray demonstrate the pharmaceutical industry’s ongoing commitment to innovation. “BioDuro continues to explore and implement these cutting-edge techniques to develop more efficient and reliable drug formulations,” says Dr. Yang.
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