Background/Objectives: To improve the potential therapeutic efficacy of albendazole (ABZ), its low solubility in alkaline environments should be addressed. Spray drying has been widely applied to increase the solubility of poorly soluble drugs. Eudragit^® E PO (EudE) has previously been used to increase the solubility of weakly basic drugs, alone and in combination with organic acids. In the present work, we aimed to demonstrate that EudE and tartaric acid (TA) significantly increase the solubility of ABZ via spray drying. Furthermore, a colon-delivery formulation was applied to deliver ABZ at pH 7.2. Methods: This study developed spray-dried formulations of ABZ-TA-EudE. The formulation with the best solubility profile was selected and loaded into the EUDRACAP^® colon to achieve colon-delivery of the ABZ formulation with enhanced solubility at basic pH. The physicochemical characteristics and in vitro drug release were evaluated and compared with those of the respective physical mixtures. Results: The addition of TA further enhanced the solubility of ABZ-EudE formulations. Both EudE and TA significantly increase ABZ solubility. The ternary ABZ-TA-EudE formulation with the best solubility, when delivered into the EUDRACAP^® colon, showed enhanced ABZ release at pH 7.2. Enhanced in vitro drug release at basic pH and physicochemical characteristics were observed for the spray-dried formulation of ABZ-TA-EudE compared with the corresponding physical mixture and the ABZ powder. Conclusions: TA and EudE significantly enhance the solubility of the weakly basic drug, ABZ, in a spray-dried formulation. Furthermore, the application of EUDRACAP^® colon is effective for colon-delivery of ABZ, as it ensures ABZ release at pH 7.2, thereby providing enhanced formulation’s solubility at its site of action.