Lipid-Based Formulations:
When and Why to Use Them
for Poorly Soluble Drugs
Poor aqueous solubility is a known factor that limits bioavailability and therapeutic potential of many new drug candidates. To overcome this challenge, lipid-based formulations (LBFs) provide a solution to enhance solubility, improve absorption rates and offer greater flexibility across various dosage forms.
As a leading CDMO, at Aenova, we specialize in LBFs and other innovative formulation technologies to help our partners bring poorly soluble drugs to market. In this article, we discuss all the challenges related to LBFs and how and when you should consider them.
What Are Lipid-Based Formulations?
LBFs are drug delivery systems in which the active pharmaceutical ingredient (API) is either dissolved or dispersed in lipid excipients. Using surfactants and co-solvents to further enhance solubility, stability, and bioavailability, they mimic the body’s natural lipid absorption mechanisms to significantly improve the oral delivery of poorly water-soluble drugs.
Types of Lipid-Based Formulations
LBFs encompass several formulation types.
Simple oil-based solutions or suspensions involve dissolving or suspending the API in a single or blended lipid vehicle, with emulsion-based systems using a combination of oil, water, and surfactants to create thermodynamically or kinetically stable mixtures.
More advanced systems include self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS), and self-nanoemulsifying drug delivery systems (SNEDDS), which spontaneously form emulsions or nanoemulsions in the gastrointestinal tract (GI) upon contact with aqueous fluids.
Common Dosage Forms
LBFs can be delivered in a variety of oral dosage forms. These include soft gelatin capsules, which are well-suited for liquid formulations; hard gelatin capsules, which can be filled with semi-solid or self-emulsifying formulations; and tablets, which can be produced by converting LBFs into solid intermediates. Additionally, LBFs can be processed into granules, powders, or pellets for further formulation flexibility.
Key Advantages of Lipid-Based Formulations for Oral Drug Delivery
LBFs enhance oral bioavailability through several complementary mechanisms.
They maintain poorly soluble drugs in a solubilized state to effectively bypass the dissolution step that typically limits absorption in conventional formulations. By keeping the drug in solution throughout its transit in the GI tract, LBFs increase the likelihood of consistent and efficient uptake. The digestion of lipids in these formulations stimulates bile secretion and promotes the formation of mixed micelles, which act as carriers to transport the drug across the intestinal epithelium to further enhance absorption.
For highly lipophilic drugs, LBFs can also enable lymphatic transport through a route that bypasses hepatic first-pass metabolism to significantly increase systemic drug exposure and improve therapeutic outcomes. In addition, maintaining drug solubilization - regardless of food intake or inter-individual differences in GI physiology - LBFs can minimize food effects and inter-patient variability for more predictable pharmacokinetic profiles.
Beyond bioavailability enhancement, LBFs offer several other advantages. Encapsulation in lipid excipients and enteric coating of the capsule can also protect sensitive APIs from hydrolysis or enzymatic degradation in the GI tract, improving stability. In addition, modified biodistribution through lipid carriers can reduce systemic toxicity by limiting drug exposure to sensitive tissues. From a manufacturing perspective, LBFs are compatible with scalable, industry-standard processes and can be readily integrated into existing capsule and tablet production lines.
When Can You Use Lipid-Based Formulations?
LBFs are most suitable for APIs that present specific physicochemical challenges. These include compounds that are highly lipophilic - typically with a log P value greater than 4 - and those with poor water solubility, often classified as Biopharmaceutics Classification System (BCS) Class II or IV. Lipid-based formulations are also advantageous for thermolabile APIs, those unstable in aqueous environments, at risk of recrystallization, with low oral bioavailability, or requiring controlled release. In all these cases, traditional formulation strategies may be ineffective or impractical.From a development standpoint, lipid-based formulations are particularly valuable when conventional bioavailability enhancement techniques - such as granulation, salt formation, or particle size reduction - fail to produce sufficient improvements in drug absorption. They are also appropriate for APIs that exhibit significant food effects or high inter-subject variability.
LBFs offer an efficient path for early-stage drug development through their ability to improve solubility and bioavailability quickly, making them an ideal choice when rapid formulation is needed to support early clinical studies or when accelerated timelines are required for development and market entry.
Considerations for Lipid-Based Formulation Development
Although lipid-based drug delivery systems offer significant advantages for poorly soluble drugs, they come with specific challenges that must be addressed during development.
Not all APIs are compatible with lipid-based systems, and each API must be carefully screened to determine its solubility and stability within various lipid excipients. Formulation development can be complex; success requires specialized expertise in selecting appropriate lipid excipients, optimizing emulsification techniques, and assessing both physical and chemical stability over time.
Regulatory considerations play a critical role too. Developers must conduct thorough characterization and validation of the formulation to ensure it meets all regulatory requirements, including those related to safety, efficacy, and manufacturing consistency.
Aenova’s Expertise in Lipid-Based Formulations
LBFs are a powerful and flexible solution for overcoming the solubility and bioavailability limitations that often hinder drug development, with their ability to enhance absorption and therapeutic performance makes them an increasingly valuable tool for modern pharmaceutical pipelines.
At Aenova, we offer comprehensive support for lipid-based drug development through our integrated CDMO services. From API characterization to pre-formulation studies, our GMP-compliant manufacturing services are well suited to the challenges of lipid-based formulations, supported by our broad technology portfolio which covers a range of advanced formulation techniques for lipid-based systems that can be tailored for product performance.
We also offer the Aenovation® program - a proprietary platform designed to accelerate the development of poorly soluble drugs, providing rapid API profiling, formulation screening, and early clinical supply to help partners move quickly through early-stage development.
By combining advanced formulation technologies with integrated CDMO capabilities, Aenova offers a strategic advantage to developers. With end-to-end support, proven expertise, and a commitment to quality, we enable pharmaceutical companies to accelerate development timelines and deliver effective therapies to patients with greater confidence and consistency.
Managing multiple vendors adds complexity and risk. But choosing an integrated CDMO offers major advantages in terms of speed, communication, and quality continuity. A partner that combines all the essential functions under one umbrella minimizes project handovers, reduces timelines, and ensures that knowledge is retained throughout the lifecycle of the program.
A seamless handoff between development phases is particularly critical when facing tight deadlines or managing global supply chains, and it also enables more responsive decision-making by aligning all stakeholders within a single organization.
Aenova offers true end-to-end services under one umbrella. From early-stage development and clinical trial supply management to commercial production, our services are fully integrated and supported by global regulatory compliance. This streamlines project handovers and preserves institutional knowledge throughout the development journey.
Regulatory Experience and Global Compliance
Drug product development is as much about documentation and compliance as it is about scientific innovation.
A CDMO with global regulatory experience and a strong track record of successful filings with regulatory agencies (such as the FDA, EMA, and PMDA) will help you navigate the global regulatory landscape. It’s essential that your CDMO can demonstrate that they understand regional requirements, submission formats, and the expectations of different health authorities, with the ability to anticipate regulatory hurdles and proactively design development programs.
Aenova’s regulatory support experts are involved early in the development process to ensure that all activities align with current guidelines and future submission requirements. Our global network of GMP-certified facilities routinely undergoes inspections and support international regulatory submissions.
Flexible Capacity and Scalability
A strong development partner should be able to scale with you - not just in volume, but in complexity and geographic reach. Early-stage programs may require only small-scale GMP batches, but as a products advance through clinical phases and moves toward commercialization, the demands on manufacturing capacity, quality systems, and supply chain coordination grow substantially.
Identify a partner with a proven track record of supporting scale-up from clinical to commercial scale, with global infrastructure and regulatory approvals in place to ensure continuity and minimize the risks and delays associated with technology transfer or switching vendors mid-development.
With more than 15 manufacturing sites worldwide, Aenova offers flexibility at every stage of the product lifecycle. We can support small-scale pilot batches, clinical supply for Phases I–III, and full-scale commercial manufacturing – all with the same high quality and technical rigor.
Robust Project Management and Communication
Transparent communication and effective project management are critical for keeping development programs on track, particularly when working across multiple sites or regulatory jurisdictions. A capable CDMO should provide structured governance models, dedicated project managers, and clear communication channels to ensure alignment at every stage.
Proactive risk identification and contingency planning are especially important in complex drug development projects where unforeseen technical or regulatory challenges can emerge. Look for a partner that not only provides regular, data-driven updates but also demonstrates accountability and responsiveness in addressing issues as they arise.
Aenova assigns dedicated project managers to every client, serving as a single point of contact and ensuring cross-functional alignment. We use structured project plans, regular milestone reviews, and digital collaboration tools to ensure accountability and transparency.
Customization and Client-Centricity
No two drug development programs are alike - and your CDMO partner should recognize that from the outset. A client-centric CDMO goes beyond offering standard services; it collaborates closely with you to understand the unique scientific, regulatory, and commercial context of your molecule.
Whether it’s adapting formulation strategies for a challenging API, aligning manufacturing approaches with your target market, or navigating region-specific regulatory pathways, a tailored approach is essential to de-risk development and maximize success.
At Aenova, we don’t believe in the one-size-fits-all model. Our teams work closely with clients to understand the unique technical, commercial, and regulatory requirements of each program. Whether you need formulation optimization, alternative dosage forms, or accelerated development timelines, we tailor our approach to your goals.
A Culture of Quality and Continuous Improvement
A CDMO with a true culture of quality treats compliance as a baseline and strives for continuous improvement through robust quality systems, data integrity, and proactive deviation management. This includes regular internal audits, real-time analytics, digital quality management systems (QMS), and a commitment to ongoing training across all staff levels.
Look for a CDMO that demonstrates not only strong historical audit performance but also a forward-looking approach to foster a culture of accountability and innovation.
Aenova’s quality systems exceed global standards, and our culture of continuous improvement drives innovation and compliance. Our facilities are regularly audited by customers and authorities, with outstanding results.
Why Aenova?
With over 4,000 employees across 15 sites in Europe and the U.S., Aenova is one of the world’s leading CDMOs for drug product development and manufacturing. Our full-service model, global compliance network, and deep technical expertise enable us to support clients at every step of their development journey.
Ready to move your product forward? Contact us to learn how Aenova can help bring your drug to market – efficiently, reliably, and compliantly.
LinkedIn
Instagram
Facebook