Ouch! That’s a big needle.
For drug formulations that are viscous in nature the solution often employed to enable injections is a large bore needle, as the needle size is the dominant single part of a syringe defining how hard you need to push on a plunger rod to get the drug out. But it needn’t be.
But how viscous is viscous? Conversations with our clients highlight that what is regarded as viscous is extremely subjective and varies enormously from person to person and company to company, often influenced by prior experiences and misconceptions. At the recent Controlled Release Society Conference in Valencia I was surprised to hear that in some quarters a formulation is still regarded as viscous when it is as low as 20cP. The reason for this is that when an auto-injector is required to facilitate the injection process some auto-injectors, that use spring based technologies, can struggle to deliver formulations of this viscosity. At Bespak, we apply our VapourSoft® technology in various device formats so we are able to deliver formulations through relatively fine needles up to 1000s of cP, and that really is viscous!
What makes a formulation highly viscous?
Some liquids flow more easily than others do. For example, honey is very “thick” and flows very slowly. Water is very “thin” and flows very quickly. One is more viscous than the other. A liquid with a high internal resistance to flow is described as having a high viscosity and a liquid with a low internal resistance to flow is described as having a low viscosity. The internal resistance is related to the ability of molecules to rearrange and move past each other which is necessary for flow. Liquids made up of small molecules tend to have a low viscosity and liquids with long chain molecules have a much higher viscosity. This is because the molecular chains get tangled up in each other like spaghetti and in order for the liquid to flow, the molecules must first unravel. Viscosity is also governed by the strength of intermolecular forces and especially by the shapes of the molecules of a liquid. Liquids whose molecules can form bonds with each other are usually more viscous. Honey, mostly glucose and fructose, is a good example of a liquid which owes its viscosity to internal bonding.
What types of pharmaceutical formulations are highly viscous?
There are a number of formulation types that are viscous and these are described below:
- Formulations containing high concentrations of large molecules
The growth in biologics, including monoclonal antibodies (MAbs), has driven the need for therapies to be administered by injection. In many cases there is also a desire for patients to be able to receive their medication away from the physician’s office and due to the impracticalities of intravenous administration this really means utilisation of the subcutaneous route. Since the volume that can be delivered with a syringe or auto-injector as a single injection into the subcutaneous tissue is limited (generally regarded as 2ml or less) higher doses drive the need for high concentrations of the drug (MAb). This generally leads to formulations with viscosities in the range of 20-100cP because biologics, that are large molecules, do tend to form bonds and get tangled up with each other.
- Formulations designed to provide sustained/controlled release
For many therapeutics that are rapidly cleared from the body it is desirable to reduce the frequency of injection by controlling the rate of release of the active agent from the site of injection. Many of these controlled release formulations include high molecular weight polymers and that also renders the formulations highly viscous. Viscosity of these formulations can be 100s or even 1000s of cP.
- Non-aqueous formulations
For some formulations the solvent itself is highly viscous. Oil based formulations may be needed to generate controlled release characteristics or alternatively as solvents for poorly water soluble drugs. The viscosity of these formulations is similar to the viscosity of the oil, for example the viscosity of castor oil is in excess of 2000cP.
How to overcome the challenge of injecting highly viscous drugs
At Bespak, we have identified the need for solutions that enable these viscous formulations to be delivered with relative ease and limited pain to users. Many device manufacturers claim to be able to deliver viscous formulations but a great deal of care needs to be taken because they may be achieving this simply by using a rather large needle which can contribute to pain and a poor user experience. The Hagen–Poiseuille equation is the physical law that gives the pressure drop in an incompressible and Newtonian fluid in laminar flow flowing through a long cylindrical pipe of constant cross section. Since the pipe is actually the needle small increases in the radius of the needle can significantly reduce the pressure required to deliver the drug and is therefore often the solution utilised by device suppliers for the drug to be delivered.
However, our VapourSoft technology takes a different approach as it allows a much higher pressure to be used to power drug delivery through a fine needle whilst reducing the risks of syringe breakage and prevent stalling of the device. Use of a liquefied gas as the “power source” rather than a spring used by most other auto-injectors provides these advantages. More details of the available devices using VapourSoft can be found here.
Recent years have seen a trend towards more viscous formulations but the number of available solutions that allow these to be administered by people other than the healthcare professional remain limited. Bespak’s VapourSoft driven devices offer an alternative to spring based auto-injectors and bring with them advantages that allow extremely high viscosity formulations to be injected through fine needles. This improves the user experience, for both the patient and the person administering the dose.