Antidiabetic tablet from Cinnamon bark and Aonla fruit

Abstract

Diabetes mellitus is a chronic metabolic disorder marked by persistent hyperglycemia due to insulin resistance, impaired secretion, or both. Affecting nearly 25% of the global population, it poses a significant burden in developing countries like India. Conventional therapies like oral hypoglycaemics and insulin are effective but often cause adverse effects such as gastrointestinal discomfort, hypoglycaemia, weight gain, and hepatic complications. Their high cost and limited accessibility in low-resource settings also hinder long-term adherence. In response to these limitations, plant-based interventions have gained attention due to their affordability, safety, and cultural acceptance. Notably, Cinnamomum verum (cinnamon bark) and Emblica officinalis Gaertn. (aonla) have been recognized for their antidiabetic potential. Cinnamon contains cinnamaldehyde, which improves insulin sensitivity and glucose uptake, while aonla fruit contains polyphenols and ascorbic acid that support antioxidant defence and metabolic regulation. The present study aimed to develop and evaluate a novel antidiabetic tablet using standardized extracts of both plants, offering a safer alternative. Research was conducted through systematic experiments at institutions in the Department of Postharvest Management, College of Agriculture, Vellanikkara, Kerala Agricultural University, Thrissur, the Department of Pharmacology, Hanagal Shri Kumareshwar College of Pharmacy, Bagalkot, Karnataka, and the Department of Postharvest Management, University of Horticultural Sciences, Bagalkot, Karnataka. In the first experiment, the study focused on the extraction procedures for cinnamon bark and aonla fruits to isolate and preserve the bioactive compounds using maceration with ethanol and water as separate extraction techniques. Preliminary phytochemical screening revealed that ethanol extracts contained a broader spectrum of bioactive compounds such as phenols, tannins, flavonoids, saponins, alkaloids, carbohydrates, proteins, steroids, ascorbic acid, and terpenoids, compared to aqueous extracts. A combination of ethanolic extracts of cinnamon bark and aonla fruit led to a synergistic interaction between their phytochemicals, resulting in enhanced yield and potency compared to individual extracts. Quantitative analysis revealed that total phenol content was 352.80 mg gallic acid equivalents (GAE) per gram, total flavonoid

content was 12.70 mg quercetin equivalents (QE) per gram, total tannin content was 175.00 mg tannic acid equivalents (TAE), and the antioxidant activity was 397.02 mg ascorbic acid equivalents (AAE) per gram. The extract had a pH of 4.70, moisture content of 5.99%, and water activity of 0.34, suggesting an additive effect due to the combination of extracts. These results were further substantiated by High-Resolution Liquid Chromatography-Mass Spectrometry (HR-LCMS), which identified major constituents such as cinnamaldehyde, eugenol, and coumarin in cinnamon bark, and gallic acid, ellagic acid, and ascorbic acid in aonla fruit. These compounds are widely recognized for their antioxidant, anti-inflammatory, and hypoglycaemic effects, making them ideal plant materials for antidiabetic formulations. In the second experiment, antidiabetic tablets were developed using ethanolic extracts of cinnamon bark and aonla fruit (1:1 ratio), combined with excipients like microcrystalline cellulose, stevia, talcum powder, and methyl paraben. Pre- and post- compression evaluations of the tablets ensured pharmaceutical quality and consumer acceptability. Pre-compression parameters such as bulk density, tapped density, Carr’s index, Hausner ratio, and angle of repose were evaluated to assess powder flowability and compressibility. The result indicated that the treatment F1A3 (150 mg with 15 mg stevia) recorded better flow properties with bulk density of 0.443 g/cm³, tapped density of 0.511 g/cm³, Carr’s index of 13.723%, Hausner ratio of 1.154, and angle of repose of 34.548° than the tablet formulation of F2B3 (300 mg with 15 mg stevia) and F3C4 treatment (600 mg with 25 mg stevia). Post-compression parameters of the tablets, such as hardness, compactibility, thickness, diameter, uniformity of weight, friability, and disintegration time, were evaluated. Among all the tablet formulations, F1A3, F2B3, and F3C4 treatments exhibited the most appropriate in line with Indian Pharmacopeia standards. The F1A3 treatment (150 mg with 15 mg stevia) recorded hardness of 4.305 kg/cm², compactibility of 42.173 N, thickness of 4.152 mm, diameter of 6.057 mm, uniformity of weight at 147.384 mg, friability of 0.332%, and disintegration time of 16.093 minutes which was superior compared to F2B3 treatment (300 mg with 15 mg stevia) and F3C4 treatment (600 mg with 25 mg stevia). Fourier Transform Infrared Spectroscopy (FTIR) confirmed chemical stability of key bioactive compounds with

no signs of degradation or interaction with excipients. Sensory evaluation by semi- trained panellists identified formulations of F1A3 (150 mg with 15 mg stevia), F2B3 (300 mg with 15 mg stevia), and F3C4 (600 mg with 25 mg stevia) as the most acceptable formulations in terms of appearance, colour, taste, texture, flavour, and overall acceptability. In the third experiment using a diabetic animal model, the treatment F1A3 (150 mg/kg body weight) had superior therapeutic effects. Body weight of rats increased by 3.54%, indicating metabolic recovery, while food intake decreased by 24.84%, suggesting restored appetite regulation. Glycaemic control improved significantly with a 16.71% reduction in serum glucose levels, total cholesterol decreased by 52.42%, triglycerides by 45.58%, low-density lipoprotein (LDL) by 59.91%, and very low-density lipoprotein (VLDL) by 0.45%, while high-density lipoprotein (HDL) increased by 11.34%, reflecting a healthier lipid profile and reduced cardiovascular risk. Protein metabolism improved, evidenced by a 5.16% increase in serum total protein and a 6.25% decrease in alkaline phosphatase activity. Antioxidant potential of the tablet formulations was confirmed by reduced lipid peroxidation and enhanced activity of superoxide dismutase and glutathione, indicating mitigation of oxidative stress. Histopathological analysis revealed restoration of pancreatic islet architecture and reduced inflammation, confirming that the tablet formulation of 150 mg/kg body weight had protective and regenerative effects on β-cell morphology and function. In the fourth experiment, the stability of the optimized antidiabetic tablet formulation (F1A3; 150 mg with 15 mg stevia) was assessed for three months under ambient (28-30 °C) and cold (5-7 °C) storage conditions. Structural integrity, biochemical composition, and sensory quality of the tablets were better under cold storage conditions. Physicochemical parameters remained stable, with a pH of 4.705, water activity of 0.304, and moisture content of 4.985%. Retention of bioactive compounds such as total phenolics (337.925 mg GAE/g), total flavonoids (12.133 mg QE/g), antioxidant activity (389.132 mg AAE/g), total tannins (163.224 mg TAE/g), total ash (5.679%), and total sugar content (0.213%) was also better under cold storage conditions.

Post-compression parameters revealed hardness of 4.193 kg/cm², compactibility of 41.109 N, thickness of 4.198 mm, diameter of 6.053 mm, and weight uniformity of 146.208 mg, friability of 0.341%, and disintegration time of 15.903 minutes, which were within acceptable limits. Microbial safety was consistently maintained throughout the storage period. Tablets stored under cold conditions showed lower microbial counts even three months after storage, with a bacterial count of 25.23×10³ CFU/g, yeast count of 18.05×10¹ CFU/g, and fungal count of 19.32×10¹ CFU/g, which were within FSSAI safety limits. Sensory evaluation further emphasized the advantages of cold storage. The mean total scores of the tablets under ambient and cold conditions were 47.8 and 53.3, respectively. This underscores the importance of controlled storage environments in maintaining the long-term efficacy and consumer acceptability of herbal formulations. In conclusion, the optimized tablet formulation of F1A3 treatment (150 mg/kg body weight) demonstrated remarkable therapeutic efficacy, robust pharmaceutical quality, and excellent storage stability, positioning it as a promising natural intervention for diabetes management. The formulation significantly improved glycemic control, lipid metabolism, liver function, and antioxidant defence, while also promoting pancreatic tissue regeneration, as evidenced by histopathological examination. These multifaceted benefits highlight the potential of the tablet as a safe and effective antidiabetic agent. Furthermore, stability studies revealed that cold storage conditions (5-7 °C) effectively preserved the tablet’s biochemical integrity, physical properties, and sensory evaluation during storage.