Achieving Tablet Stability with Moisture Management
Moisture is one of the biggest challenges you face as a drug manufacturer. Some active pharmaceutical ingredients (APIs) possess an increased sensitivity to moisture. This – along with other environmental factors – poses significant risks to your product stability. Manufacturing processes, environmental considerations and product packaging are all key factors that impact moisture management.
Typically, the primary method used to combat environmental moisture is physical packaging containing low permeability moisture barrier materials and desiccants. While effective at reducing the impact of air, light or moisture, these barriers and moisture-absorbing materials are a packaging-based solution. Their effectiveness is subject to variability in shelf life and dependent on an API’s sensitivity to other environmental conditions. Overly complex physical barrier solutions also raise the total cost of manufacture.
Did you know, however, that during manufacturing you can now build in multiple layers of moisture protection without adding significant cost through appropriate design of the dosage form?
Understanding Good and Bad Moisture in Tablets
Many scientists believe that moisture content directly impacts moisture-induced degradation. Total moisture content (loss on drying or LOD) is often used to assess the potential stability of moisture-sensitive products. However, the total moisture content of pharmaceutical products typically includes both bound (i.e.: water of hydration, linked by hydrogen bonding or entrapped into an amorphous structure) and free water.
Free water is responsible for the degradation of moisture sensitive materials, which can result in poor drug stability profiles. Unlike its bound form, water in a free (or mobile form) is available for chemical reactions with other materials. So – when considering the stability of moisture sensitive drugs – free water content and the degree of water activity provide more valuable information than the total moisture content.
Managing Moisture - From Core to Coating
Before investing in costly packaging solutions, simple formulation improvements can often bring significant stability benefits for the drug product and reduce cost impact.
Lower Water Activity to Improve Core Stability
While Starch 1500 ®, partially pregelatinized starch has a relatively high moisture content, it has very low water activity – providing better stability for moisture sensitive actives. The moisture scavenging properties of Starch 1500 (by hydrogen bonding inside its amorphous structure) make it an excellent excipient to enhance stability. By inhibiting water activity within the formulation and retarding interaction with the moisture sensitive API, Starch 1500 helps to reduce or eliminate the detrimental effects of other excipients.
The Role of Film Coating in Moisture Protection
Development of film coating formulations that can be applied with minimal ingress of water and protection from humidity offer additional moisture defense and enhance stability.
A recent study discussed a comparison of uncoated and coated placebos for film coating moisture barrier properties, using on-tablet dynamic vapour sorption (DVS) models to measure water sorption. The study found that the uncoated tablets had the fastest rate of water sorption, while all coated tablets showed significantly lower WVTR (water vapor transmission rate) values. The big takeaway, however, was that coatings utilizing “polyvinyl alcohol (PVA) as the film-forming polymer showed vast improvements in moisture barrier properties over traditional HPMC-based coatings.”
Moisture Protection In-Use: A Case Study
The rate and level of moisture uptake is a solid indicator of moisture barrier film coating performance. Colorcon presented a study looking at the impact of film coatings as a factor in moisture protection for amoxicillin/clavulanic acid dosage forms.
The study evaluated the in-use stability of uncoated, HPMC-based coated, and Opadry® amb II (PVA) coated tablets. The performance of the three different tablet coatings was compared following removal from primary packaging, at daily intervals for 10 days.
At the end of the 10-day dosage regimen, the clavulanic acid in the uncoated and HPMC coated tablets was totally depleted, but the tablets coated with PVA based coating, Opadry amb II, maintained acceptable levels of both clavulanic acid and amoxicillin even outside of the primary packaging. Results confirm that Opadry amb II protects the integrity of moisture-sensitive compounds beyond the primary packaging.
The study also evaluated accelerated stability of HPMC-based coated, and Opadry® amb II (PVA) coated tablets on two blister packaging materials with different degrees of permeability to moisture vapor (alu-alu and Aclar blister). After 6 months, tablets coated with Opadry amb II showed passing assay results in both packaging methods.
Reduce Tablet Stability Challenges
Tablet stability is an ongoing challenge due to the growing class of moisture-sensitive APIs coming to market in which exposure can lead to degradation, stability issues, and poor efficacy. Knowing the moisture sensitivity of your drug formulation can help you determine the best methods to control it.
Choosing the right excipients and tablet coatings can help. Manufacturers should consider using a combination of a moisture scavenging excipient like Starch 1500, alongside a specialized tablet coating such as Opadry amb II as a cost-effective solution to protect the integrity of moisture-sensitive compounds.