Preparation, characterization, and pre-clinical evaluation of acarbose-guar gum solid dispersions in diabetic rats

Acarbose, a clinically approved α-glucosidase inhibitor for type 2 diabetes, has limited efficacy due to gastrointestinal side effects, highlighting the need for delivery systems that modulate release and improve tolerability. This study aimed to develop and characterize acarbose-guar gum solid dispersions (AGSDs) and evaluate their physicochemical, in vitro, and in vivo properties. Solid-state characterization confirmed amorphous molecular dispersion with spherical particles and drug-polymer interactions. Among the developed solid dispersions, AGSD-3 showed the highest drug entrapment efficiency (84.24 ± 0.48%) and controlled release (86.19 ± 1.66% over 24 h), compared to free acarbose. It exhibited strong enzyme inhibition with IC₅₀ values of 6.97 ± 0.21 μg/mL (α-glucosidase) and 12.86 ± 0.18 μg/mL (α-amylase), along with favourable cytocompatibility and hemocompatibility. In high-fat diet (HFD)-fed, streptozotocin (STZ)-induced diabetic rat model, AGSD-3 at 50 mg/kg significantly reduced body weight and blood glucose (p < 0.001), while gastrointestinal side effects, such as diarrhoea, were limited to a single day (score 1), indicating improved tolerability compared to acarbose alone. Treatment also restored pancreatic weight (p < 0.001) and histology, and attenuated oxidative stress, and inflammation (p < 0.001), indicating protective effects against diabetes-induced tissue damage. Overall, these findings suggest that guar gum-based solid dispersion represents a promising strategy to enhance the therapeutic efficacy and tolerability of acarbose for diabetes management.