Abstract:
Objective: Directly incorporating aqueous solutions into hard gelatin capsules (HGCs) without dispersing them in an
oily medium is considered a challenge for most researchers and manufacturers. The aim of the study is to evaluate the
effect of gamma radiation (ɣ-radiation) on the adaptation of HGCs for aqueous solution delivery. Methods: Empty HGC
shells were exposed to four of ɣ-radiation doses (1, 3, 5, 10 kGy). Then, the physicochemical properties of irradiated
capsules were evaluation and compared with those of non-irradiated capsules. Fourier-transform infrared spectroscopy
(FT-IR), capsule hardness, and water incorporation tests were performed. In-vitro disintegration/dissolution behavior
determined as (rupture time) in different dissolution media was evaluated. Results: The results showed direct
proportionality between the ɣ-radiation dose and HGC crosslinking degree up to 3 kGy, while at doses >3 kGy,
degradation rather than crosslinking occurred. The results were clearly demonstrated by FTIR as peptide linkages
between gelatin molecules. All the ɣ-irradiated HGCs submitted to hardness test were completely deformed without
rupture with increasing capsule deformation work (J) for γ-radiation doses up to 3 kGy; the deformation work declined at
doses >3 kGy. The water incorporation study revealed that capsules exposed to 3 kGy could hold up to 100 ml of
methylene blue solution without deformation or leakage for 45 minutes compared with non-irradiated HGCs, which
showed a significantly lower tolerance of only 2 minutes (p<0.001). The crosslinking of HGCs had a minor significant
effect on in-vitro rupture time, especially at gastric pH. Conclusion: The irradiation technique may be used not only for
sterilizing HGCs but also for adapting HGCs for aqueous solutions delivery, as it showed a significant positive effect,
which was optimal at a dose of 3 kGy. However, these results are not sufficient for scaled-up manufacturing; thus, further
investigations are strongly recommended.