Proprietary Technologies For Drug Products
The CDMO Division of LLS Health employs a wide range of non-proprietary technologies to tackle clients’ bioavailability and formulation challenges. At times, clients may be looking to utilize a patented technology as part of their intellectual property strategy or they may face a problem that needs a specialized technique. In these cases, LLS Health offers several proprietary technologies that may meet clients’ commercial and technical needs.
LLS Health’s proprietary SteriMill™ nanomilling technology employs high energy media milling (AKA nanomilling) to reduce particle size and increase the dissolution rate of poorly water-soluble APIs. The technology uses custom miilling equipment that enables aseptic production of nanosuspensions from R&D through commercial scale—a benefit that cannot be achieved with traditional mills.
Nanomilling is a nearly-universal, top-down approach to solubility enhancement with several benefits, including:
- NO harsh organic solvents or pH extremes: Most nanomilled suspensions are aqueous-based
- High API concentrations: 5-40+% API (w/w)
- Easy Scale-Up: Nanomilling utilizes a recirculation process that allows batch sizes to increase without changing process variables
- Reproducibility: Once a nanomilling process is optimized, there is minimal variation in particle size from batch-to-batch
The technology behind nanomilling was developed in the 1980s and the first FDA-approved nanocrystal drug came to market in 2000. Since then, numerous BCS class II and IV APIs have benefitted from nanomilling and gained FDA approval. Nanomilling has been used to increase bioavailability and minimize fed/fasted variability in both liquid and solid dosage forms.
The Apisolex polymer is an injectable-grade poly(amino acid) based co-polymer that has been shown to increase the solubility of hydrophobic APIs by up to 50,000 times where other commonly-used excipients fail.
Robustly patented, safe, efficient, and scalable, Apisolex formulations can achieve drug loading up to 40%, dramatically increase the achievable concentration of API in water, and reconstitute in saline in less than 30 seconds.
Lubrizol’s Apinovex polymers are GMP-validated, high molecular weight polyacrylic acid excipients designed to provide both processing and formulation benefits for spray-dried amorphous solid dispersions (ASDs).
Apinovex polymers enable formulators to achieve stable, high drug loading (up to 80%) and up to 10x improvement in drug release for crystalline APIs. With Apinovex, formulators can develop efficient, IP-protected oral solid dosage forms for a range of poorly soluble APIs.
Our Surface Arrayed Therapeutics (SATx™) technology offers a simpler, more versatile approach to “linking” a biological molecule with an API compared to more traditional methods such as antibody-drug conjugates (ADCs). ADCs involve covalently attaching an antibody to a drug molecule, which alters the molecule. The new molecular entity (NME) created requires extensive characterization, accompanied by increased regulatory challenges that are associated with a NME. With SATx technology, a drug is encapsulated in a lipid nano- or micro-particle using a straightforward process. When an antibody or other biological molecule is attached to the particle, it is done so electrostatically, so no conjugation chemistry is involved, and the drug is unaltered.
While both SATx technology and ADCs offer the ability to target tissue in the body with high specificity, only SATx technology can handle dramatically higher drug loading. This technology can deliver a broader range of pharmaceuticals than typical ADCs, allowing for greater formulation flexibility, and the minute particle size evades rapid clearance from the body.
PEGPLUS™ (PLL-g-PEG) technology is a multifunctional excipient technology offered by the CDMO Division of LLS Health. This hydrophilic graft copolymer is comprised of a poly(L-lysine)-backbone with poly(ethylene glycol) side chains, resulting in an overall positively charged molecule at neutral pH. The positive charge allows it to bind to negatively charged surfaces1-3, such as those found on mucous membranes like the cornea,3-4 and nucleic acids like DNA and RNA. The adhesive functionality of PEGPLUS technology is highly desired in drug delivery as it can:
- Prolong drug exposure to a biological surface, therefore increasing bioavailability3,4
- Coat surfaces to prevent unwanted adhesion of cells and bacteria1-3
- Protect and stabilize therapeutic agents in the human body5
PEGPLUS technology has many applications in vitro and in vivo and has proven to be safe and effective in multiple formulations3-5. This technology has received particular attention in ophthalmic applications, as it has been shown to successfully bind to the cornea for extended drug and moisture retention3-4.
- Pasche, S., et al. Poly(l-lysine)-graft-poly(ethylene glycol) assembled monolayers on niobium oxide surfaces: a quantitative study of the inﬂuence of polymer interfacial architecture on resistance to protein absorption by ToF-SIMS and in situ OWLS. Langmuir. 19:9216–9225, 2003.
- Huang, N.-P., et al. Poly(l-lysine)-g-poly(ethylene glycol) layers on metal oxide surfaces: surface-analytical characterization and resistance to serum and ﬁbrinogen adsorption. Langmuir. 17:489–498, 2001.
- Gensheimer, W. G., et al. Novel formulation of glycerin 1% Artificial Tears extends tear film break-up time compared with Systane Lubricant Eye Drops. Journal of Ocular Pharmacology and Therapeutics, 28(5), 473–478, 2012.
- Kleinman, D., et al. Dry eye syndrome: A review & novel formulation approach. Drug Development and Delivery. 12(8), 86-92, 2012.
- Sato, A., et al. Polymer brush-stabilized polyplex for a siRNA carrier with long circulatory half-life. Journal of controlled release : official journal of the Controlled Release Society. 122. 209-16, 2007.