Hygroscopicity
Classification:
Hygroscopicity is classified into various types based on the extent of moisture uptake under specific conditions of temperature and relative humidity (RH).
On the basis of the European Pharmacopoeia (Ph. Eur.), categorizes materials after being stored at 25°C and 80% RH for 24 hours:
Non-hygroscopic: Increase in mass is less than or equal to 0.2% w/w.
Slightly hygroscopic: Increase in mass is greater than 0.2% w/w and less than 2.0% w/w.
Hygroscopic: Increase in mass is greater than or equal to 2.0% w/w and less than 15.0% w/w.
Very hygroscopic: Increase in mass is greater than 15.0% w/w.
Another classification system by Callahan et al. categorizes hygroscopicity based on the percentage weight gain after one week at different relative humidity levels:
Non-hygroscopic: No increase in weight at RH < 90% and < 20% increase at RH > 90%.
Slightly hygroscopic: Detectable increase at RH < 90% and 20-50% increase at RH > 90%.
Hygroscopic: Significant increase at RH < 90% and 50-100% increase at RH > 90%.
Deliquescent (Very Hygroscopic): Absorbs enough moisture to form a liquid solution.
Effect of Hygroscopicity on Product Quality:
Hygroscopicity can significantly impact the quality of pharmaceutical products in various ways:
Physical Stability:
Caking and Clumping: Moisture absorption can lead to the formation of solid bridges between particles, causing powders and granules to cake or clump. This affects flowability, making processing (e.g., tablet manufacturing, capsule filling) difficult and can lead to weight variations in dosage units.
Changes in Solid State: Hygroscopic materials can undergo changes in their crystalline form (polymorphic transitions), form hydrates (if water is incorporated into the crystal lattice), or even become amorphous. These changes can alter solubility, dissolution rate, and stability.
Increased Volume: Water uptake can cause swelling of materials & volume increase.
Chemical Stability:
Hydrolysis: Absorbed moisture can act as a reactant or a catalyst for hydrolytic degradation of drugs and excipients, leading to the formation of impurities and a reduction in the active drug content, thus affecting the efficacy and safety of the product.
Microbial Contamination: Increased moisture content can create a favorable environment for the growth of microorganisms, leading to product spoilage and potential health hazards.
Dissolution and Bioavailability: Changes in the
solid state or the formation of hydrates due to hygroscopicity can alter the
drug's solubility and dissolution rate, which are critical factors for its
absorption and bioavailability.