Ternary solid dispersion to improve solubility and dissolution of meloxicam

Abstract

Background Meloxicam (MLX) is a potent non-steroidal anti-inflammatory drug with poor solubility. Solid dispersion (SD) is an effective formulation strategy to improve the dissolution rate of poorly water-soluble compounds. Hydroxy propyl methyl cellulose (HPMC) as an inert polymer carrier and nicotinic acid (NA) as disturbance can be used as a matrix of SD. The aim of this study was to determine the effect of MLX-HPMC-NA SD on the solubility and dissolution of MLX. Methods SD was prepared by the solvent evaporation technique with methanol being used as a solvent. Methanol was evaporated at room temperature. SD of MLX was prepared involving various matrix compositions at MLX:HPMC:NA ratios of 1:1:1 (SD1), 1:1:2 (SD2), 1:2:1 (SD3), and 1:2:2 (SD4). Results The solubility profile of MLX in SD3 (64.34 ppm) showed a higher improvement than the physical mixture (15.99 ppm) and pure MLX (6.89 ppm). This increase might be due to the formation of molecular dispersion of MLX in the polymer as hydrophilic matrix and NA have both donor-acceptor sites for hydrogen bonding interactions. The dissolution profile of SD3 also showed the highest improvement. The melting endotherm of SD3 was detected at 219.5 °C, in which case it originated from NA rather than from MLX, showing that MLX was molecularly dispersed and amorphous. Conclusions MLX solubility and dissolution profile could be improved by the SD technique with a matrix of HPMC and NA. The best result was given by SD3 with an MLX:HPMC:NA ratio of 1:2:1. Based on the characterization study, it is predicted that hydrophilic polymer and hydrogen bonding interactions play important roles in MLX solubility or dissolution rate improvement.

Binary or ternary mixture of solid dispersion: Meloxicam case

“…The results suggested the formation of amorphous solid dispersion. These results were consistent with previous report (Setyawan et al 2019). Moreover, these results suggested that the addition of water insoluble polymer (ethylcellulose) could prevent the recrystallization process (Hameed 2017).…”

Solubility Enhancement of Diclofenac Using Solid Dispersions

“…The results of the solubility test on S1, S2 and S3 observed in distilled water were 0.485, 0.2186, 0.1748 respectively as shown in table 3. It was noted that the solubility of the prepared solid dispersion decreased as the ratio of carrier increases [35][36][37].…”

Fundamental Aspects of a Third Component Used in Ternary Solid Dispersion: A Review

“…The carrier used in combination with a ternary agent could be a polymer, surfactant or a polymer with surfactant property [32,33]. Examples of ternary agents comprise surfactant [34], polymer [35], adsorbent [36], pH modulator [37] and hydrotropic agent [38]. Various international publications of the past decade are summarized from the reputed source (Elsevier, Pubmed, NCBI) to emphasize the significance of the key components (ternary agents) particularly, surfactants, polymers, pH modulators, and adsorbents to improve TSD's reliability in addressing the challenges of formulation associated with the drug solubility and dissolution.…”