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Rising to the Solubility Challenge: Collaborative Solutions in API Development
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In the continuously evolving world of pharmaceuticals, poor molecule solubility remains a significant challenge. Imagine this: researchers discover a promising drug with the potential to treat a life-threatening disease, but its poor water solubility threatens to halt its journey from lab to pharmacy shelf. This is not just a scientific puzzle—it’s a shared challenge that requires collaboration, technical expertise, and a flexible approach.
At Polpharma API, we recognize that solubility issues are a common hurdle in drug development. As a API producer and CDMO partner, we work closely with our partners to address these challenges together. Our role is to support, adapt, and provide a broad range of technical solutions tailored to the needs of our partners.
A Growing Problem in Drug Development
The statistics are compelling: nearly 90% of new chemical entities (NCEs) are classified as poorly water-soluble. The increasing complexity of drug discovery has led to a surge in lipophilic molecules—compounds designed to interact with complex biological targets but struggling to dissolve in the aqueous environment of the human body.
For API producers like Polpharma API, this trend presents both a challenge and an opportunity to support our partners in overcoming formulation barriers. Solubility is a critical factor in drug absorption and bioavailability. Poorly soluble drugs often face delayed absorption and limited therapeutic impact, making the need for effective solutions more urgent than ever.
A Broad Toolbox of Solubility Enhancement Techniques
Industry offers a wide array of techniques to help address solubility challenges. These methods are selected and applied based on the specific properties of the API and the formulation goals of our collaborators.
1. Process Design Optimization
By optimizing particle size distribution (PSD) and refining manufacturing processes, we help ensure consistent API performance and improved dissolution characteristics.
2. Solubilizers
Solubilizers such as surfactants are incorporated into formulations to increase solubility. These agents reduce interfacial tension, allowing APIs to disperse more uniformly in aqueous environments.
3. Bypassing Strategies: Prodrugs, Lipids, Encapsulation, Complexation, and Drug Carriers
- Prodrugs involve chemically modifying APIs into derivatives with improved solubility or permeability, which are then converted into the active drug in the body.
- Complexation, such as with cyclodextrins, traps APIs within soluble host molecules, enhancing solubility and protecting them from degradation.
- Lipid-based delivery systems (e.g., emulsions, liposomes) encapsulate APIs in absorbable carriers, improving bioavailability.
- Carrier systems like micelles, dendrimers, and nanoparticles stabilize APIs in suspension and promote targeted delivery.
4. Micronisation and Nanoparticles
Reducing APIs to microscopic or nanoscopic scales increases their surface area, enhancing dissolution rates. This is akin to turning boulders into grains of sand—easier to break down and absorb.
5. Co-Grinding and Physical Solutions
Co-grinding combines APIs with excipients to improve wettability and reduce particle size. This cost-effective method enhances dissolution by mechanically altering the API’s physical properties.
6. Amorphous Solid Dispersions
Transforming crystalline APIs into amorphous forms disrupts their crystal lattice, significantly enhancing solubility. This technique is a powerful tool in the formulation of poorly soluble drugs.
7. Co-Crystals
Co-crystallization involves combining APIs with co-formers to create new crystalline structures. This approach improves solubility while maintaining stability, leveraging the complementary properties of different materials.
8. Salt Formation
Converting APIs into ionizable salts is a well-established method for improving solubility and bioavailability. It remains a simple yet effective strategy in many development programs.
9. Solid Form Modifications
Modifying the solid form of APIs—such as transitioning between polymorphs or creating hydrates and solvates—can lead to substantial improvements in solubility and stability.
Collaboration as a Core Strategy
Solving solubility challenges is not just about applying the right technology—it’s about working together. At Polpharma API, we actively collaborate with universities, technology providers, and pharmaceutical companies to co-develop tailored solutions. Our role is to provide the technical foundation and manufacturing flexibility that our partners need to succeed.
We bring physico-chemical expertise across a wide range of solubility enhancement techniques, from micronisation to advanced solid-form modifications. Our goal is to integrate these capabilities into the broader development strategies of our partners, helping them bring effective therapies to market.
Turning Challenges into Opportunities
The race to overcome solubility barriers continues to inspire innovation and collaboration. For Polpharma API, addressing poor solubility is not just a technical task—it’s a shared mission to support our partners in delivering high-quality, accessible medicines to patients worldwide.
We are committed to working hand-in-hand with FDF producers and other stakeholders to meet specific formulation needs. Whether through early-stage development, scale-up, or commercial manufacturing, we are ready to support your goals with a flexible, collaborative approach.
Let’s tackle the solubility challenge—together.
Author
Head ofthe Solid State Chemistry Team
Technology Development Department
Polpharma API BU
Disclaimer
Products protected by patents (SPC) in Poland are developed solely for the purpose of Regulatory Submissions or R&D purposes intended to support Regulatory Submissions. These products are not offered for sale or made available in countries where such products are subject to patent (SPC) protection and where the offer for sale or any related activity constitutes patent infringement. It is within the buyer’s responsibility and liability to check the patent situation of the product in the import market(s).
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