How would you define lipid based drug delivery?
Lipid Based Drug Delivery (LBDD) is a multi-disciplinary approach, a congregation of organic chemistry, physics, bio pharmaceutics, and formulation technologies surrounding the function of fatty acids, fatty acid esters, and their assemblies—with the aim of improving drug release and absorption.
What are the applications for lipid-formulations?
The traditional forms of LBDD may be found in nutritional supplements, sustained release tablets, ointments, suppositories and creams, among others. The contemporary use of LBDD however, encompasses a host of systems including liposomes, lipid nanoparticles, self-emulsifying lipid formulations (SELF), solid dispersions, dry emulsions, solid-liquid compacts, and drug-lipid conjugates.
A most prominent application for lipids is in oral bioavailability enhancement where the aim may be increased solubility, targeting lymphatic transport, and or modulation of enterocytes-based drug transport and disposition.
What factors drive interest in lipid-based formulations?
The drug development tool kit continuously expands to meet the growing specificity of new drugs. The need for flexibility of formulation choices, patentability of new dosage forms, and most importantly the emergence of complex new drug entities are the important factors driving the interest in the field.
How does lipid-based drug delivery address oral bioavailability challenges?
Lipid formulations have the potential to improve drug solubility, permeability and absorption. Bioavailability enhancement is achieved by the solubilisation of the drug in the gut milieu, facilitated by the micellization of the lipids. This protects the drug from falling out of solution; improves the drug affinity for the protective aqueous monolayer lining the lumen; and ameliorates the conditions for the drug to cross the intestinal wall due to enhanced membrane fluidity.
Additionally, lipids can improve drug permeability by inhibiting/ saturating the enterocyte based transporters; or significantly increase bioavailability by promoting lymphatic absorption of highly lipophilic drugs that would otherwise be eliminated pre-systemically.
What are the key recent developments in lipid-based drug delivery?
The understanding of the physico-chemical and biopharmaceutical role of lipids in drug delivery has significantly improved. Evolving capsule shell technologies have largely addressed the manufacturing viability/stability of liquid and semi-solid formulations. The horizon for supersaturating lipid systems and lipid solid oral dosage forms development is expanding. Further, novel investigational tools for predicting drug absorption and guiding formulation development have emerged.
Why has full commercial adoption of lipid-based formulations for oral bioavailability been an uphill battle?
Among the top challenges has been the lack of investigational tools to correctly classify, characterize, and predict the in vivo performance of the lipid formulations.
Nevertheless, lipid based formulations have done well compared to other approaches, accounting for ~50% of new drug approvals involving solubilisation. This suggests that the prevalence or absence of lipids on the market is not a reflection of their efficacy but rather indicative of a widespread systemic “resistance to change” permeating all aspects of drug development.
What are your thoughts on the future of lipidbased drug delivery?
As solubilizers, bioavailability enhancers, or drug release modifiers, lipids have a promising future. They offer versatility of formulation choices beyond the conventional techniques, among them: melt granulation/pelletization, spray cooling, hot melt coating, melt extrusion, and preparation of solid lipid nanoparticles using high pressure homogenization. There is also a large potential for lipids in multi-particulates and multi-layered dosage forms.
Describe the work you do with regard to this field.
We are a global provider of excipients and formulation solutions, specializing in lipid-based drug delivery for all routes of administration. Our aim is to succeed by staying current with the market needs. For example, we provide extensive safety and regulatory support by creating new product monographs. We are the first—if not the only— excipient manufacturer that has created guidelines for preclinical studies involving lipids. Our R&D and application laboratories continue to publish in peer reviewed scientific journals. We also collaborate with industry and academia to improve the protocols for classification, design, and evaluation of lipid formulations. Gattefossé is the founder and sponsor of the St-Remy conferences for 48 years and remains an active participant in professional association affairs for programming and scientific achievement awards.