Compatibility study of rosmarinic acid with excipients used in pharmaceutical solid dosage forms using thermal and non-thermal techniques

Abstract

Rosmarinic acid (RA) is a phenolic compound that presents well-documented anti-inflammatory, antioxidant and antitumor activities, and based on its pharmacological potential and poor bioavailability, several solid dosage forms have been developed to RA delivery. Therefore, in literature, there are no reports about RA compatibility with excipients. In this regard, the aim of the present study was to evaluate, for the first time, the compatibility of RA with excipients commonly used in solid dosage forms at a 1:1 (RA:excipient) ratio using differential scanning calorimetry (DSC), thermogravimetry (TG), Fourier-transform infrared (FTIR), solid-state nuclear magnetic resonance (ssNMR), and isothermal stress testing (IST) coupled with liquid chromatography (LC). The excipients selected were hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), lactose monohydrate (LAC), polyvinylpyrrolidone (PVP), talc (TALC), croscarmellose sodium (CCS), and magnesium stearate (MgSTE). According to DSC results, physical interactions were found between RA and HPMC, LAC, CCS, and MgSTE. The TG analyses confirmed the physical interactions and suggested chemical incompatibility. FTIR revealed physical interaction of RA with TALC and MgSTE and the ssNMR confirmed the physical interaction showed by FTIR and excluded the presence of chemical incompatibility. By IST, the greatest loss of RA content was found to CCS and MgSTE (>15%), demonstrating chemical incompatibilities with RA. High temperatures used in DSC and TG analyses could be responsible for incompatibilities in binary mixtures (BMs) with HPMC and LAC, while temperature above 25 °C and presence of water were factors that promote incompatibilities in BMs with CCS and MgSTE. Overall results demonstrate that RA was compatible with MCC and PVP.

Formulation Effects in the Antioxidant Activity of Extract from the Leaves of Cymbopogon citratus (DC) Stapf

“…The excipients used in the formulation were chosen by the pre-formulation assays in the DSC and FTIR-ATR studies. Of the four excipients, only lactose monohydrate showed a possible interaction with the extract (Figure 2); the lactose curve demonstrated three endothermic events related to dehydration (146.82 • C), melting (218.99 • C) and thermal decomposition (240.86 • C), respectively, which were identical to the results obtained by Pereira et al [30] and may suggest chemical incompatibility [31].…”

Inhibitory Effect of a Rosmarinic Acid-Enriched Fraction Prepared from Nga-Mon (Perilla frutescens) Seed Meal on Osteoclastogenesis through the RANK Signaling Pathway

“…RA is an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid that can be widely found in many plants, especially rosemary, perilla, basil, and mint [ 48 ]. RA possesses remarkable pharmacological activities, such as antioxidant and anti-inflammation properties, and with regard to neurodegeneration, cancer, diabetes, and bone diseases [ 48 , 49 , 50 ]. Our studies analyzed the RA level of each PSM fraction, with results showing that the SMEF contained the highest amount of RA, followed by SME, SMWF, SMHF, and SMDF, as shown in Table 3 .…”

“…Antioxidant activity as IC50 and ferric reducing/antioxidant power (FRAP) of perilla seed meal (PSM) fractions determined by different assays using ascorbic acid and rosmarinic acid (RA) as the positive control. ABTS, 2,2-azino-bis-3ethylbenzthiazoline-6-sulfonic acid; SMEF, seed-meal ethyl acetate fraction.…”

Rosmarinic acid improves boar sperm quality, antioxidant capacity and energy metabolism at 17°C via AMPK activation

“…RA is a water-soluble polyphenolic phytochemical with free-radical scavenging and antioxidant effects (Veras et al, 2019). Al-Alami et al (2017) showed that RA had a reversal effect on metronidazole-induced infertility in male albino rats.…”

“…RA is a water‐soluble polyphenolic phytochemical with free‐radical scavenging and antioxidant effects (Veras et al., 2019). Al‐Alami et al.…”