Calling the Shots: Innovation in Controlled-Release Injectables - Pharmaceutical Technology

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Calling the Shots: Innovation in Controlled-Release Injectables
High demand could lead to innovation in controlled-release injectables.

Pharmaceutical Technology
Volume 35, Issue 7, pp. 36-41

The PRINT technique

The pharmaceutical industry has frequently benefited from technologies developed in other industries. The method called Particle Replication in Nonwetting Templates (PRINT), which is based on technologies used to make transistors for the computer industry, potentially could be applied to making controlled-release injectable drugs. A team led by Joseph DeSimone, a chemistry professor at the University of North Carolina at Chapel Hill, developed PRINT, which gives companies increased control of the size and shape of drug particles.

Particle replication in nonwetting templates can produce shapes that mimic (left) red blood cells and (right) metastatic cancer cells. (IMAGES ARE COURTESY OF JOSEPH DESIMONE AND TIMOTHY MERKEL OF THE UNIVERSITY OF NORTH CAROLINA)
In this technique, scientists pour a drug solution into a template that forms particles with the desired dimensions and form. The solution is sometimes formulated with surfactants or lipids, and the resulting particles are colloids that are either stabilized sterically (e.g., through the incorporation of polyethylene glycol) or electrostatically (i.e., though a charge), says DeSimone. Formulators disperse these particles in phosphate buffer.

When an emulsion is used to create PLGA microspheres, a fraction of the drug usually separates into the polymer, thus trapping it and preventing it from being released. The amount of drug loaded into PLGA microspheres is consequently limited because it is difficult to control partition coefficients. In contrast, the PRINT technique enables manufacturers to make PLGA particles that contain 40% drug. "That's three or four times higher than anyone in the literature has been able to achieve," says DeSimone.

One way that scientists can control drug release from a PRINT particle is by using degradable polymers, such as PLGA, as the particle matrix. The polymer's properties can be exploited or modified to achieve the desired release profile. The electrostatic interactions and the solubility characteristics between the particle matrix and the drug cargo that it contains can be adjusted. The more similar the polymer's characteristics are to those of the drug, the higher solubility the drug will have in the polymer. Another method would be to incorporate prodrugs into the PRINT particles. Formulators choose prodrug linkers with the appropriate rates of degradation to ensure that the drug is released from the carriers at the desired rate.

Particle size and shape also can affect a drug's release rate because different sizes and shapes have different surface-area-to-volume ratios. "Generally, if one has a set volume of particle, decreasing particle size will increase the available surface area for water contact, and thus increase the release rate," says DeSimone. Shapes, such as spheres, which minimize surface area to volume, have decreased drug-release rates, he adds. Through the PRINT technique, surface-area-to-volume ratios can be adjusted to achieve the required release rate for the product.


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