To treat hypertension around 75% of patients will require combination therapy for which administration of lisinopril and indapamide could be of practical use. Lisinopril has a low oral bioavailability (around 25%) with large intersubject variability (6-60%), due to slow absorption. In order to improve drug permeability, encapsulation of the drugs within nanoparticles (NPs) has demonstrated great potential. For this reason we have prepared hard capsules containing both drugs: indapamide and lisinopril-loaded chitosan (CS) nanoparticles. The mucoadhesive characteristics of CS-NPs will prolong the residence time of lisinopril in contact with the intestinal membrane thereby increasing its oral bioavailability. Moreover, for their quantification a reversed-phase HPLC method is developed and validated using a C18 column. The mobile phase is prepared with methanol:water (50:50, v/v) including triethylamine (0.1% of total volume) and adjusted at pH 3.1. The calibration curves are linear over the ranges 16-24 µg.mL-1 for lisinopril and 8-12 µg.mL-1 for indapamide. Intra-day precision results in %RSD ranging 0.74-1.86 for lisinopril and 0.60-1.91 for indapamide. Recovery results obtained for lisinopril and indapamide range 98.22-102.34% and 97.35-101.00%, respectively. The LOD and LOQ are 0.4 µg.mL-1 and 1.4 µg.mL-1 for lisinopril, and 0.5 µg.mL-1 and 1.5 µg.mL-1 for indapamide. The HPLC method is simple, easy to apply, rapid, with UV detection, and allows for quality control of the new formulation developed. The method can be applied for the quantification of this drug combination in medicinal products.