This article is part of a special feature on packaging that was published in the May issue of PTE Digital, available at http://www.pharmtech.com/ptedigital0511.
The process for assuring that a packaged drug will remain stable throughout its expected shelf life is long and difficult. Sometimes a pharma company will have comprehensive knowledge of the mechanisms of degradation for the drug substance or drug product, and will be able to surmise whether a sorbent is required. However, forced degradation studies are often performed to determine whether or not a sorbent is required. Either way, the exact type and quantity of sorbent is often unknown by the company, which leads to the need for sorbent-ranging studies to optimise the sorbent type and quantity.If empirically-derived data on the drug product is readily available, modelling can be performed to assist with sorbent selection in a given packaging presentation, which can save time and money.
Sorbent selection is often an afterthought in the development process; however, it is beneficial to incorporate the correct sorbent in the early stages of the process. Pseudo-empirical modeling provides the means to accomplish this because it can provide an analytical model of the permeation and adsorption of moisture, which can be used to determine the proper sorbent type and capacity needed to achieve the targeted shelf life of a given drug product or drug–device combination product.
Formulation chemists and packaging engineers must work together in this effort because the drug product, container and sorbent function together as a system. The sorbent will reduce or otherwise manage the Equilibrium Relative Humidity (ERH) and/or oxygen in the packaging headspace, but it will also manage free-moisture in the drug product; thus, managing molecular mobility and chemical degradation. The sorbent must also compensate for the increased rate of ingress of moisture or oxygen through permeable packaging brought on by its use. Modeling simulates how all the interdependent variables will affect one another over time.
This Quality by Design approach allows manufacturers to quickly determine which sorbent solutions are required. This eliminates the need for sorbent ranging studies and, ultimately, expedites the commencement of registration stability testing and regulatory submission.
Traditionally, a desiccant packet placed in the drug product packaging would be sufficient to protect the product from moisture. But with today's new drug formulations and progressive packaging configurations companies need the sorbent to fill the role of an intelligent environmental manager. Multiple undesirable environmental conditions can present within the package headspace, such as free-moisture, oxygen and volatiles, which must all be successfully managed.
Intelligent sorbents are specifically formulated to achieve a desired outcome. Maintaining specific ERH within the packaging presentation is required for the stability of some drug products; for example, amorphous drug substances that undergo oxidation can improve their chemical stability upon hydration. Though aggressive management of moisture in solid state is suitable for moisture-mediated oxidation for most drug substances, doing so with amorphous substances would result in decreased stability. In such cases, the use of an intelligent sorbent formulation combining oxygen management with moisture regulation in the package headspace provides an optimised chemical and physical stability profile of the final drug product.
In another scenario, a pharmaceutical formulation may need a sorbent to remove volatilised hydrocarbons. All of these cases require an optimised sorbent formulation that can intelligently manage the packaging or device headspace by reacting to environmental changes.
Some drugs have multiple conditions that must be managed. For instance, moisture and oxygen may need to be removed while allowing a specific hydrocarbon to remain. Another example is a combination drug product where two drug substances are combined into a single dose. These formulations can require complex, multifunctional, intelligent sorbents.
In addition to sorbent chemistry, the sorbent device configuration must continually evolve with the demands of the changing market. In many applications, a drop-in solution such as a sachet or canister will work well. With some drug delivery systems, this is not a feasible approach and a fit-in solution is required where sorbent is compressed and shaped to fit into an available space in the packaging or drug device. A third option is a built-in solution where a desiccant-loaded polymer is used to make a component of the packaging or device.
The commercial success of a pharmaceutical is dependent upon protecting the drug from degradation. The important thing to remember is that sorbent selection is a complex process that involves many interdependent variables and nothing should be left to chance.