Development and Optimization of a Green Co-Processed Orange Peel Pectin–Flaxseed Mucilage Carrier for Solubility and Dissolution Enhancement of Candesartan Cilexetil

Background

Candesartan cilexetil (CC) is a BCS Class II drug with low aqueous solubility, which is a large problem for dissolution and oral bioavailability. Sustainable plant-derived excipients commercially derived from agro-waste can be considered as an environmentally friendly alternative to the conventional synthetic solubility-enhancing systems.

Aim

To formulate and optimize orange peel pectin–flaxseed mucilage as a carrier for improvement of solubility and dissolution of CC.

Methods

Extraction of pectin and flaxseed mucilage was done using aqueous process and co-processing was carried out at 25:75, 50:50 and 75:25 ratio. The drug:carrier ratios were 1:1, 1:2 and 1:3 and the CC solid dispersions were prepared by the 3² factorial design. The practical yield, the drug content and the saturation solubility and in-vitro dissolution were tested. FTIR was used for the characterization of the optimized system.

Results

Pure CC was soluble in pH 7.4 phosphate buffer (0.48 mg/mL) and 0.1 N HCl (0.34 mg/mL). The solubility of F8 (1:3 drug:carrier; 50:50 pectin:mucilage) was the highest (0.86 and 1.24 mg/mL, respectively) which is about 2.53 and 2.58 fold increase with drug content of 99.0%, practical yield of 91.2% and drug release of 94% at 120 min.

Conclusion

The proposed approach involves agro-waste utilization, natural polymer engineering and factorial optimization, for developing a sustainable carrier for poorly soluble drugs. The optimized system is expected to offer an interesting green alternative to enhance the dissolution of CC.