Abstract
Background: Albendazole (ABZ) is a broad-spectrum benzimidazole anthelmintic characterized by very low aqueous solubility, which can limit its dissolution and oral bioavailability. PAMAM dendrimers have the potential to improve the apparent solubility of poorly water-soluble drugs through their highly branched structure and multiple surface functional groups.
Aim: This study aimed to investigate the effects of PAMAM dendrimer surface group, generation, drug:dendrimer ratio, solvent pH, and methanol percentage on the solubility of albendazole using a Design of Experiments (DoE) approach.
Methods: A two-level factorial DoE comprising 16 experimental formulations was conducted. The investigated factors were dendrimer surface group (NH₂ or COONa), generation (G3 or G4), drug:dendrimer ratio (1:1 or 3:1), pH (2 or 7.5), and methanol percentage (0% or 10%). Formulations were prepared and maintained at 25°C with continuous stirring at 100 rpm for 24 h in the orbital shaker incubator. Following filtration of undissolved material, the concentration of dissolved ABZ was determined using UV–Vis spectrophotometry at 297.3 nm.Results: Albendazole solubility varied markedly among the experimental formulations, ranging from 9.02 to 403.00 μg/mL. The highest solubility (403.00 μg/mL) was obtained with COONa-G3 PAMAM, a 3:1 drug:dendrimer ratio, pH 2, and 10% methanol. ANOVA demonstrated that solvent pH was the most influential factor (F = 575.36, p < 0.0001), followed by drug:dendrimer ratio (F = 129.78, p < 0.0001) and methanol percentage (F = 9.91, p = 0.0093). In contrast, surface group (F = 1.42, p = 0.2681) and dendrimer generation (F = 1.19, p = 0.3065) were not statistically significant. The results showed substantially higher ABZ solubility at pH 2 compared with pH 7.5 across the tested formulations.
Conclusion: PAMAM dendrimer incorporation substantially enhanced the apparent solubility of albendazole under the investigated conditions. The DoE approach identified pH and drug:dendrimer ratio as the major formulation variables, while surface group and dendrimer generation showed no statistically significant effects. The formulation containing COONa-G3 at a 3:1 ratio and pH 2 achieved the highest observed ABZ solubility.
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