Extrusion force dictated by manufacturing

August 1, 2007

The ease or difficulty with which one can push a hyaluronic acid dermal filler through a syringe depends largely on factors such as the substance's hardness and viscosity, both of which are determined by the manufacturing process, an expert says.

Irvine, Calif. - To understand the injection characteristics of a hyaluronic acid (HA)-based dermal filler and how the material performs clinically, one must understand how it was made, an expert says.

To help dermatologists understand the concept of gel hardness, Dr. Tezel explains that if one sandwiches an HA gel between two plates, the higher the gel's G value, the more force it will take to push the top plate a small distance horizontally while holding the bottom one stationary. More specifically, he says G denotes the ratio of shear stress (force per unit area of the plate) to the shear strain imposed (the ratio of the horizontal displacement to the vertical distance between plates).

Part of the solution to this problem involves incorporating some unmodified or uncross-linked HA, which flows much more easily than HA with molecules that are cross-linked, Dr. Tezel tells Dermatology Times.

However, he says, "The downside of using uncross-linked HA is that it doesn't provide persistence and is rapidly broken down in the skin. So in the ideal filler, one wants minimal amounts of uncross-linked HA."

Cross-linking limitations

Cross-linking refers to the process by which U.S. manufacturers bind HA polymer chains to each other, currently by using either 1,4-butanediol diglycidal ether (BDDE) or di-vinyl sulfone (DVS), Dr. Tezel explains.

Both react with hydroxyl sites on HA chains, thereby slowing down enzymatic, mechanical and free radical degradation of dermal fillers after they're injected into the skin, he adds.

"Besides adding uncross-linked HA," Dr. Tezel says, "another point of differentiation between manufacturers is how they size down the gel mass" that results from linking HA polymer chains together. If they don't do this, he notes, "It will just clog the needle."

One approach to breaking down HA gel mass involves pushing it through sieves or screens.

The screens have openings of a certain size and shape that create particles of roughly corresponding size and shape, Dr. Tezel says. "That specifically sized particle creates a gel with a granular consistency."

In contrast, he says Allergan does not use screens to specifically size its HA gel. Rather, Dr. Tezel says, "We create random sizes and shapes" through a proprietary homogenization process.

"By creating random sizes and shapes," he explains, "we create a uniform consistency or a smooth-looking gel. The only HA product in the United States that uses this type of formulation is Juvéderm."

If one looks at this product under a microscope, Dr. Tezel says, "One will not see it as a granular particle product. One will see a very smooth formulation."

Manufacturing influences

Manufacturing processes affect not only how an HA filler extrudes, but may also affect how the product feels to the patient inside his or her skin, Dr. Tezel says.

Products manufactured by sieving techniques have a narrow distribution of gel particle sizes and usually a higher viscosity unless they include additional uncross-linked HA, he says. However, Dr. Tezel adds, "The uncross-linked HA will be quickly metabolized and won't contribute to long-term clinical outcome."