Formaldehyde, glutaraldehyde, and ketones are preferably used
in the preparation of chemically-cross linked PVOH Hydrogels [16].
However, these are toxic, and the amount of residual cross linker
left in the final polymer, and ways to reach to an acceptable and safe
concentration can be quite challenging. Apparently, the molecular
weight between the two crosslink points or crosslink density determines
the final polymer properties such as the capacity of swelling, mechanical
strength, rate of drug release, and its stability. However, such desirable
properties are compromised by increased level of hydrogel toxicity
and complicated purification at higher crosslinker concentration.
Residual crosslinkers due to their functionality and reactivity have
a strong potential to react with bioactive or drugs, and can alter the
therapeutic properties of the final dosage form. Several studies have
been conducted to evaluate the effect of crosslinking agents on drug
diffusion, drug release and general properties of Hydrogels [17,18]