Zero-order drug delivery: State of the art and future prospects

Pharmaceutical drugs are an important part of the global healthcare system, with some estimates suggesting over 50% of the world’s population takes at least one medication per day. Most drugs are delivered as immediate-release formulations that lead to a rapid increase in systemic drug concentration.

Highlights

• A critical review of translational zero-order drug delivery systems.

• Summary of the current state of common drug delivery devices.

• Discussion of the techniques being employed to advance towards zero-order release.

• Insight on the future of zero-order drug release.

Although these formulations have historically played an important role, they can be limited by poor patient compliance, adverse side effects, low bioavailability, or undesirable pharmacokinetics. Drug delivery systems featuring first-order release kinetics have been able to improve pharmacokinetics but are not ideal for drugs with short biological half-lives or small therapeutic windows. Zero-order drug delivery systems have the potential to overcome the issues facing immediate-release and first-order systems by releasing drug at a constant rate, thereby maintaining drug concentrations within the therapeutic window for an extended period of time. This release profile can be used to limit adverse side effects, reduce dosing frequency, and potentially improve patient compliance. This review covers strategies being employed to attain zero-order release or alter traditionally first-order release kinetics to achieve more consistent release before discussing opportunities for improving device performance based on emerging materials and fabrication methods. Continue on zero-order drug delivery

Source:

Mei-Li Laracuente, Marina H. Yu, Kevin J. McHugh, Zero-order drug delivery: State of the art and future prospects,
Journal of Controlled Release, Volume 327, 2020, Pages 834-856, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2020.09.020.

Zero order kinetics of drug release
Zero order release kinetics refers to the process of constant drug release from a drug delivery device such as oral osmotic tablet, transdermal system, matrix tablet with low soluble drugs and other delivery system. Constant release is defined in this context as the same amount of drug release per unit time. In its simplest form, zero order drug release can be represented as in equation 3:

C= C0+k0t

Where C is the amount of drug released, C0 is the initial amount of drug in solution and k0 is the zero-order constant.  

First order kinetics equation of drug release
The release of drug which follows first order kinetics can be represented by the equation 4

DC/dt=-K1C

K1 is the first order rate constant, expressed in time-1 or per hour. Hence it can be defined as that first order process is the one whose rate is directly proportional to the concentration of drug undergoing reaction i.e., greater the concentration faster the reaction. Hence, it follows linear kinetics. After integrating and rearranging the equation becomes as shown in equation 5.

log C=log C0-K1t/2.303

C0 is the initial concentration of the drug, C0 is the percent of drug remaining at time t. The correlation coefficient of the above equation will give the information whether the drug release follows first order kinetics or not.