Issue link: https://www.e-digitaleditions.com/i/626800
28 January 2016 Tablets & Capsules weeks when it should typically have a shelf life of 2 years. Given the pressure to innovate and get to market quickly, identifying the causes of degradation and the best approaches to slow them can be a challenge. That's where sorbent technologies can help. They slow the mechanisms of degradation in drug products and signif- icantly improve stability, enabling you to obtain the shelf life required. Supported by Quality-by-Design simulations, sorbents are an inexpensive and fast way to stabilize drug products. In fact, the predictive ability of simulations can eliminate costly sorbent ranging studies and shorten the time to market. To see how sorbent technology can help, it's important to understand the mechanisms of degradation and how they affect drug product stability. Degradation pathways Pharmaceuticals are subject to a variety of degradation pathways that can shorten shelf life and raise safety issues. Hydrolysis is the most common degradation pathway, accounting for 60 to 80 percent of all reactions, followed by oxidation at 20 to 30 percent (most of them moisture- mediated) [1]. Other pathways include isomerization, photo-degradation, and elimination. Determining the mechanisms of degradation solely for the active pharma- ceutical ingredient (API) requires studying its solution kinetics (sensitivity to temperature and pH). But when the API is formulated into a tablet or capsule, solid-state degra- dation comes into play, and that is more complex and diffi- cult to predict. Critical factors involved in solid-state degradation include: moisture level, excipient incompatibilities, nucle- ation, and auto-catalysis from degradants that have high entropy and reactivity. Other possible factors include the drug product's formulation, the processes used to manufac- ture it, how it is packaged, and the type of environments to which it's exposed during storage and transportation. Impact of formulation. In addition to the API, tablets and capsules typically include a variety of excipients, including binders, disintegrants, lubricants, and coatings. All contain some free moisture and, depending on how the product is made, moisture levels can increase, such as dur- ing the wet granulation process. Very few tablets have an optimal free-moisture level when they leave the press. Plus, when molecular mobility is sufficient to allow solid-state reactions, any additional free moisture will increase molecular mobility and thereby accelerate degra- dation. In fact, molecular mobility is directly related to the formulation's moisture content: The higher the moisture content, the faster the reaction rate and the greater the like- lihood of auto-catalysis. Impact of packaging. How a product is packaged also affects its moisture level, and imperfect seals are typically the largest-single contributor to the ingress of moisture. But moisture can also pass through the plastic packaging itself, typically expressed as the moisture vapor transmission rate (MVTR) and denoted in grams per square meter per day. Other sources of moisture include the internal packaging material (dunnage) and the air within a bottle's initial head- space (Figure 1). Although high-barrier packaging materi- als—primarily films for blister packs—reduce the ingress of moisture and oxygen, they are also more expensive than high-density polyethylene bottles that incorporate sorbents. The value of sorbent simulations Sorbents reduce moisture and therefore molecular mobility, slowing the rate of degradation and improving drug product stability. (The greater the stability, the longer the shelf life.) Whatever the pathways of degradation hap- Figure 1 Sources of moisture in packaging The seal. The primary route of most moisture ingress is via imperfections in the seal. Products packaged in an HDPE bottle that doesn't have a foil-laminate induction seal are up to eight times more vulnerable to moisture. Transmission through the plastic resin Initial package headspace The product Internal packaging material (dunnage)