Over 80% of new chemical entities (NCEs) suffer from poor aqueous solubility, posing major challenges in drug formulation and bioavailability. These poorly soluble active pharmaceutical ingredients (APIs) often exhibit high melting points and elevated logP values, leading to limited absorption and low systemic exposure. Selecting the right solubilization technology is critical to enable oral and parenteral delivery of such compounds. Fortunately, Ascendia Pharmaceutical Solutions has advanced nanotechnologies (LipidSol®) and state-of-the-art manufacturing suites to effectively address these challenges. It’s part of the Ascendia Difference.
Limitations of Conventional Solubilization Technologies
Traditional approaches, such as micronization, salt formation, and cyclodextrin complexation, offer limited utility for many modern drug candidates. High lipophilicity and hydrophobicity often result in incompatibility with conventional excipients or inadequate performance in vivo. As drug candidates become more complex, advanced technologies, such as LipidSol, are required to address solubility, absorption, and stability limitations.
Lipid-Based Drug Delivery Systems for Oral and Injectable Use
Lipid-based formulations, including self-emulsifying drug delivery systems (SEDDS), nanoemulsions, liposomes, and lipid nanoparticles (LNPs), have become key enabling technologies for poorly soluble compounds. These systems enhance drug solubilization, improve lymphatic uptake, bypass first-pass metabolism, and reduce food effects.
LNPs, in particular, are increasingly favored for their high drug-loading capacity, scalability, and versatility in both oral and injectable dosage forms.
Nanosizing and Its Impact on Bioavailability
Reducing API particle size to the nanoscale significantly increases surface area and dissolution rate, translating to higher in vivo bioavailability. For example, nanosuspensions of danazol and atovaquone have demonstrated 15-fold and 2.5-fold improvements in bioavailability, respectively. These results highlight the value of nanosizing technologies for overcoming solubility and absorption barriers.
Lipid Nanoparticle Systems: SLNs and NLCs
Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are advanced colloidal delivery systems that provide enhanced encapsulation efficiency, biocompatibility, and controlled drug release. SLNs consist of solid lipids and surfactants that entrap APIs within a crystalline matrix. NLCs incorporate both solid and liquid lipids, increasing payload capacity and stability for lipophilic drugs.
These lipid-based nanoparticles are applicable across delivery routes, including oral, IV, topical, and pulmonary, and can be tailored for immediate or sustained-release profiles.
Ascendia’s LipidSol® Technology for Poorly Soluble APIs
Ascendia Pharmaceutical Solutions’ proprietary LipidSol technology enables the formulation of water-insoluble compounds for oral and injectable delivery. LipidSol includes customizable lipid-based systems such as LNPs, nanoemulsions, and liposomes, designed to enhance API bioavailability while maintaining formulation stability and manufacturability.
LipidSol is composed of lipid-based assemblies that encapsulate small and large molecules, as well as biologics in nanoparticle structures. This makes it. especially effective for APIs with poor aqueous solubility, limited absorption, or challenging pharmacokinetics. It supports scalable manufacturing and offers formulation flexibility for preclinical through commercial development.
LipidSol is also beneficial in overcoming a key issue with injectables – injection site issues. Ascendia Pharmaceutical Solutions’ scientists leverage LipidSol’s nanoemulsions, as well as its Precision Nanosystems and GMP-grade NETZSCH DeltaVita® 600 Gamma Vita equipment to help develop injectable formulations that do not result in skin reactions on patients.
Case Study: Lipid Nanoparticles for Injectable Carvedilol
Carvedilol, a poorly soluble beta-blocker, was developed by Ascendia Pharmaceutical Solutions as an extended-release injectable using LNP technology. The prescription medication is marketed under the name Coreg®. The resulting formulations exhibited controlled drug release over 24 hours and increased systemic exposure. These outcomes demonstrate the value of LNP systems for delivering challenging APIs with enhanced therapeutic profiles.
Advantages of Lipid-based Formulations
Lipid-based drug delivery offers several benefits for low-solubility APIs:
- Enhanced solubility and dissolution rates
- Improved oral bioavailability
- Reduced variability from food effects
- Avoidance of harsh processing conditions
- Long-term stability and controlled release
- Scalable, cost-effective manufacturing
Compared to amorphous solid dispersions (ASDs), lipid-based formulations often offer simpler processing, fewer excipient compatibility issues, and improved patient outcomes.
Selecting the Optimal Drug Delivery Platform
Formulation selection depends on API properties, including thermal sensitivity, lipophilicity, and solubility profile. Lipid-based nanoparticle systems are especially valuable for APIs that are not amenable to spray drying, hot melt extrusion, or polymeric dispersions. Ascendia Pharmaceutical Solutions provides these services in its Class 10,000 (ISO 7) and Class 100 (ISO 5) pharmaceutical manufacturing facilities in its North Brunswick, New Jersey, Bioscience Center headquarters.
Ascendia Pharmaceutical Solutions uses predictive modeling, accelerated stability testing, and rapid screening of lipid excipients to optimize formulation selection and reduce development timelines.
Partner with Ascendia for Lipid Nanoparticle Formulations
Ascendia Pharmaceutical Solutions specializes in enabling formulations for poorly soluble compounds. With a robust portfolio of proprietary technologies, including LipidSol®, and deep expertise in lipid-based systems, Ascendia Pharmaceutical Solutions is a preferred CDMO partner of choice for oral and injectable drug delivery.
To accelerate the development of your challenging molecule and explore lipid nanoparticle solutions, schedule a meeting with Ascendia Pharmaceutical Solutions today. We can discuss how we can be Fast, Flexible, and complete your project seamlessly the First time.