Lipids and inclusion-complexes can have complementary roles. And while they fulfill similar functions, it is their structural differences that make them suitable for achieving distinct tasks. In pharmaceutical technology, lipids and inclusion-based complexes are considered pillar excipients for the fabrication of most dosage forms, irrespective of the administration route. They play various roles ranging from support vehicles to release rate modifiers, stabilizers, solubilizers, permeation enhancers,1 and bioavailability enhancement.
The Importance of Lipid-Based Formulations
Lipid-based drug carriers can influence bioavailability through enhanced solubilization in the GI tract and reducing variability of systemic exposure. Understanding the digestion and absorption process of lipids is of great importance for interpretation of the biopharmaceutical properties of lipid-based formulations proposed for oral administration.3 Various lipid-based formulation approaches used to enhance oral drug bioavailability include 2:
- Excipients: This method involves the use of dietary oils composed of medium and long chain triglycerides, solvents and surfactants. For highly lipophilic drugs, these lipid-based excipients have been shown to be capable of increasing the fraction of absorbed drug that enters into the lymphatic system, where hepatic metabolic pathways are avoided.
- Mixed micelles: A well-designed lipid formulation presents the drug as a molecular dispersion in which the drug may be transferred to the mixed micellesystem as the formulation is diluted into aqueous phase. The surfactant components would be expected to interact with mixed bile salt micelles with the result of changing their structure and solubilization capacity.3
- Self-Emulsifying Drug Delivery System (SEDDS): Among the lipid-based formulations, self-emulsifying formulations enable drug release from the lipid phase into a solubilized phase form from the components of bile and lipolytic products.3
- Solid-Lipid Nanoparticles (SLNPs): These aqueous dispersions of solid lipid molecules have some advantages of polymeric nanoparticles, fat emulsions, and liposomes.3 Solid-lipid nanoparticles (SLN) were developed to combine the advantages of polymer nanocarriers, such as strong drug loading capacity, controllable drug delivery, good biocompatibility of lipid emulsions, and improved drug bioavailability. SLN can be prepared by a variety of technologies including heat or cold homogenization, has consistent process repeatability and does not require toxic organic solvents in the preparation process. The main feature of SLN is that it contains lipids that remain solid at room temperature. 4
The Magic of Inclusion Complex Delivery Systems
Industry insiders claim that inclusion complex delivery systems make the magic possible for drug delivery by improving the safety and efficacy through control of rate, time, and place of drug release within the body. 5
A common natural inclusion complex delivery system are cyclodextrin derivatives. Extensive studies have been performed on cyclodextrins and their complexes in the last 30 years. These starch derivatives have lipophilic inner cavities and a hydrophilic outer surface. Cyclodextrins create water-soluble inclusion complexes with hydrophobic drugs that exhibit low aqueous solubility.6 They have been shown to interact with a variety of molecules to form non-covalent inclusion complexes, resulting in decreased side effects and increased bioavailability.2
There are three types of cyclodextrins: α, β, and γ-cyclodextrins. β-Cyclodextrin is ideal for drug delivery due to the cavity size, efficient drug complexation and loading, availability, and relatively low cost.5
As presented in the examples above, your CDMO partner requires extensive knowledge and experience in oral solid dose development to help bring your drug to market. Pii’s experienced R&D team can assist in solving your formulation challenges, getting you quickly into the clinic, on time and on budget.
- Lipids and polymers in pharmaceutical technology: Lifelong companions, Juergen Siepmann, et. al., ScienceDirect, March 10, 2019.
- Bioavailability Enhancement Technologies and Services, 2022-2035, Roots Analysis.
- Design of Lipid-Based Formulations for Oral Administration of Poorly Water-Soluble Drug Fenofibrate: Effects of Digestion, Kazi Mohsin, PubMed Central, AAPS PharmSciTech, June 2012.
- A Review of Polymer and Lipid-Based Nanocarriers and Its Application to Nano-Pharmaceutical and Food-Based Systems, Hongyun Lu, et. al., National Library of Medicine, Frontiers in Nutrition, Dec. 1, 2021.
- Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics, Dixit V. Bhalani, et. al., Biomedicines 2022.
- Recent advances in polymeric drug delivery systems, Yong Kiel Sung and Sung Wan Kim, Biomaterials Research, June 6, 2020.
Pharmaceutics International, Inc. (Pii) is a US-based contract development and manufacturing organization (CDMO) located in Hunt Valley, Maryland. The experienced scientists, engineers, and staff at Pii pride themselves on adroitly employing a phase appropriate method of drug development for the prudent use of their customer’s resources as they solve challenging problems. In addition to offering end-to-end development services, Pii manufactures a variety of dosage forms to include complex parenteral drugs and has a wealth of analytical testing capabilities. Its Hunt Valley campus has four aseptic suites with lyophilization capabilities. Our talented professionals stand ready to help!