A Comparative Assessment of Capsule Formulations Based on Amorphous Solid Dispersion and Salt Formation of Indomethacin

Background: Indomethacin (IND) is a nonsteroidal anti-inflammatory drug (NSAID) that belongs to the BCS class II and exhibits poor dissolution in the GIT fluids. Solid dispersion (SD) and salt formation (SF) are two acceptable and widely used approaches for dissolution enhancement. Objective: The aim of the present study is to formulate and in vitro evaluate capsules from IND-Soluplus® SD and IND sodium SF, and compare the dissolution profile of the formulated capsules with pure IND. Methods: Both IND SD and SF were prepared by the solvent evaporation method and characterized for their production yield, drug content, in vitro release, solid state characterization, and stability studies. Capsules were prepared by manual filling into hard gelatin capsules with IND SD and IND SF used as a source for the active ingredient, lactose or mannitol as diluent, and three types of super disintegrants: croscarmellose sodium, crospovidone, and sodium starch glycolate. The prepared capsules were tested for flow properties, weight variation, content uniformity, disintegration time, and in vitro dissolution test. Results: The solvent evaporation method successfully produced IND SD and SF with high production yield and drug content, which were above 95%. Solid state characterization revealed complete amorphization of IND in the SD without any incompatibility, while it was in its crystalline state in SF. Both IND SD and SF were stable during the storage period with minor changes in drug content and drug release. The results showed proper flow properties with acceptable results for the weight variation test (all around 500 mg since it is a size 0 capsule), capsule content uniformity (98-99 %), and disintegration time (4-9 min). The disintegration of hard gelatin capsules is impacted by the type of disintegrant used, with superior performance of crospovidone (4 min) and croscarmellose sodium (5.3 min) compared to sodium starch glycolate (7.1-7.4 min). IND solid dispersion showed an enhanced dissolution (100% within 45 min) compared to the pure IND capsules (less than 50% within 45 min) and IND SF (100% within 45 min). Also, the dissolution of IND SD capsules containing crospovidone was superior to those containing croscarmellose sodium and sodium starch glycolate. Conclusions: Indomethacin SD proved its efficacy in enhancing the dissolution of IND compared to pure IND capsules and IND SF.