Preformulation studies for nortriptyline

Abstract

Nortriptyline (NRT), usually conditioned as hydrochloride, is a second-generation tricyclic antidepressant that is primarily used as a treatment option for major depression and chronic pain. In this study, a compatibility evaluation between an active pharmaceutical ingredient (API) and various excipients that form binary mixtures is presented. As investigational methods, ATR-FTIR analysis and PXRD data were recorded for the binary mixtures under ambient conditions, and were later investigated by thermal analysis (TG—thermogravimetry/DTG—derivative thermogravimetry/HF—heat flow) in dynamic air atmosphere. Nortriptyline hydrochloride (NRT) was used as an active pharmaceutical ingredient, and binary mixtures with 13 excipients from different categories were formed (mass ratio 1:1), namely: microcrystalline cellulose (MC), calcium lactate (CaLact), stearic acid (StA), lactose monohydrate (Lact), polyvinylpyrrolidone K30 (PVP), magnesium stearate (MgSt), sodium carboxymethylcellulose (CMCNa), sorbitol (Sorb), mannitol (Man), gelatine (Gel), silica (SiO2), starch (Starch), and talc (T). The PXDR patterns determined for the binary mixtures showed no incompatibility between the components since the diffraction profile consists in the superposing of the components’ patterns, while the ATR-FTIR study indicated interactions in the discussed binary mixtures, suggesting that NRT is incompatible with PVP, Sorb, Man, StA, and Lact even under ambient conditions. Under thermal stress, interactions between NRT and excipients were observed at temperatures below the melting point of the API in the binary mixtures with PVP, Sorb, Man, StA, and Lact, while at high temperatures, all binary mixtures are thermally degraded due to thermolysis.