Everything You Wanted to Know About Polymer Synthesis But Were Afraid To Ask

4 Questions to Ask Your CDMO

Posted: September 28, 2020

API Manufacturing and Pharmaceutical Manufacturing

According to the Science History Institute, the first synthetic polymer was invented in 1869 by John Wesley Hyatt, when a New York firm offered $10,000 to anyone who could provide a substitute for ivory. Since then, polymers have become ubiquitous across all aspects of our lives – from household goods, such as electronic components, plastic storage containers or bottle caps; to medical devices, such as stents and implants; and even in space exploration, for space crafts, thermal control coatings, adhesives, tapes or thermal insulations.

Biomedical applications, in particular, are a huge growth area for polymer synthesis.  They’re playing a central role in the development and manufacture of medical devices, since their flexibility, light weight, non-ferrous properties and biocompatibility are enabling the next generation of implants, single-use devices, and packaging technologies.

In addition, Contract Development & Manufacturing Organizations (CDMOs) are developing polymers for sponsors to use as the deliverers of genetic therapies. Poly (amino acids) actually can act as Active Pharmaceutical Ingredients (APIs) in and of themselves.

Polymers are everywhere but what exactly are they?  The term, polymer, is derived from the Greek word for many (poly) and parts (mer). Polymer synthesis occurs when small molecules are linked together in order to create a larger structure (a macromolecule). In other words, the method for making macromolecules from smaller substituents (monomers) is polymer synthesis. Polymers not only have similar attributes to their parent monomer, but as a result of the new architecture from the polymerization process, unique physical properties can also appear.

Innovations in Polymer Technology

Polymer chemistry is relatively new compared to organic synthetic chemistry of small molecules. It’s partly been driven by the development of other techniques like nano-technology, since nano-particles (in the range of 20-200nm) are optimal for drug delivery applications. For example, an anti-cancer polymer-drug complex using nano-particles, benefits from their enhanced permeability and retention (EPR) effect. This helps the polymer-drug complex to accumulate in the tumor tissue avoiding renal clearance.     

Since the introduction of man-made polymers, many advances have taken place, particularly in biodegradable polymers. By being able to degrade, these types of polymers can be implanted into the body without requiring additional surgeries to remove them. For example, some polymer materials are woven into pouches and then put into a medical device that is put in the body. These pouches prevent infection, which is often caused by the biofilm that naturally occurs between the human tissue and the device.

In another example, polymers to deliver insulin, anti-cancer or anti-infection drugs are being administered directly into patients. These devices help in expanding the effectiveness of the drug being delivered by controlling time, measurement, and location of the drugs in the body. The devices can be conventional or implantable, such as infusion pumps or infusion catheters such as valves, IV sets, needles or cannulas.

In addition, biodegradable polymer materials are being woven into thread for sutures, which dissolve without requiring removal. These types of applications are eliminating follow-up surgery and reducing both healthcare costs and infection risk for patients.

What Tools Does it Take to Analyze a Polymer?

The introduction of macromolecules requires a unique set of tools and skill-sets in order to properly relate the properties of the monomer to tailor the resulting polymer to meet the target specifications and characteristics. In addition to the more common analysis for small molecule API development such as NMR (liquid and solid state), IR, HPLC, etc., polymers may require other physical analyses through key technologies, which would be targeted to the very specific end-use of the polymers.  These analytical technologies may include:

  • Polymer chain characterization through Size Exclusion Chromatography (SEC)
  • Particle size analysis through Dynamic Light Scattering (DLS) technology
  • Thermal stability through Thermogravimetric Analysis (TGA) or Differential Scanning Calorimetry (DSC) 
  • Intrinsic elasticity/viscosity through Dynamic Mechanical Analysis (DM),  Rheometry) or MI measured value techniques

The Intricacies and Challenges of Polymerization

In addition to the more common challenges found in small molecule API synthesis, polymer chemistry requires an intrinsic understanding of the interactions of the microscopic and macroscopic during the synthesis process. For example, it’s important to understand that the rate of addition and dispersion forces in a reaction during scaling will impact the size and the shape of particles formed during polymerization.

Here at Seqens NA, we have many years of experience in polymer development for biomedical applications in cGMP environments, including the synthesis, optimization and characterization of the parent monomers that are then carried through to the final polymer. Below are some of the polymerization projects we’ve completed:

  • Poly(oxazolines) up to 5 kg scale using controlled polymerization (CROP) for drug excipient and gene therapies
  • Poly(β-amino esters) up to 100g in bulk step polymerization for use in gene therapies while tailoring molecular weights
  • Poly(norbornenes) based polymers up to 1kg via controlled ring-opening metathesis polymerizations (ROMP) for targeted anti-cancer treatments
  • Poly(acetals) up to 500g for use as a drug excipient
  • Poly(ester amino ureas) up to 5kg for use as biodegradable medical supports and implants
  • Poly(acrylates/methacrylates) up to 5kg using both controlled (RAFT)) and uncontrolled free radical polymerizations in biomedical supports of as a backbone for unique anti-cancer polymers
  • Poly(urethanes) as biocompatible rapid-onset glues and gels for surgical and trauma treatment

What To Ask Your CDMO About Polymer Synthesis

Given its complexity, manufacturing advanced polymers for life-saving applications is no easy task.  Before selecting a CDMO to produce your polymers, it pays to ask the following four questions:

  1. What polymer processes have you completed and can you provide references?
  2. How well do you understand the structure-property relationships of monomers and polymers for efficient optimization?
  3. Do you have access to the analytical tools to appropriately evaluate polymers to achieve target applications?
  4. Do you have GMP-certified suites?

As polymers become among the most widely used materials in medicine, innovations and continued advances increasingly will shape new applications and uses.  CDMOs with the experience , analytical capabilities and expertise to perform complex polymer synthesis projects and help you stay abreast of whatever comes next will be the key to successful projects that keep pace with modern medicine.

Want to know more about polymer-based medical device capabilities at Seqens NA? You can find more background on our projects here, or contact us at 978-462-5555.

About the Author

Robert Doyle , Polymer Research Scientists, Seqens CDMO NA (formerly PCI Synthesis)