Meloxicam-Paracetamol Binary Solid Dispersion Systems with Enhanced Solubility and Dissolution Rate:Preparation, Characterization, and In Vivo Evaluation

• Published in: Journal of pharmaceutical innovation Vol. 12; no. 3; pp. 206 - 215
• Main Authors: Al-Remawi, Mayyas, Ali, Ahmed Mahmoud Abdelhaleem, Khames, Ahmed, Hamaidi, Mohammad
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2017
• Subjects: Biochemical Engineering; Biomedical and Life Sciences; Biomedicine; Biotechnology; Industrial and Production Engineering; Original Article; Pharmacology/Toxicology; Meloxicam; Paracetamol; Analgesic; Anti-inflammatory; Dissolution; Binary solid dispersions
• ISSN: 1872-5120; 1939-8042
• DOI: 10.1007/s12247-017-9281-1

The aim of this work included the improvement of meloxicam solubility and maximizing its pharmacological activity by forming binary solid dispersions with paracetamol. Different binary solid dispersions were prepared using paracetamol as a pharmacologically related coformer with favorable structural, dissolution, and solubility properties. The prepared binary solid dispersions were characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Saturation solubility and dissolution rate were determined for meloxicam-paracetamol binary solid dispersions and compared to each drug individually. The pharmacological effects of meloxicam were enhanced in binary solid dispersions compared to the physical mixture using mice as animal models. This finding could be attributed to the improvement of meloxicam saturation solubility in the binary solid dispersion systems. Solid state characterization demonstrated the formation of amorphous phase with low crystallinity as obtained by XRD data. The solid dispersion prepared by freeze drying at 1:10 molar ratio showed more than sevenfold increase in solubility of meloxicam and more than 65% increase in dissolution rate compared to both generic preparation and physical mixture tablets. Significant differences ( P  < 0.05) in the analgesic effect represented by the increase in time of licking of forepaws to 7.92 s for the solid dispersion (SD) (F4) system compared to 6.15 and 4.82 s, for physical mixture and control groups were observed, respectively. A significant difference ( P  < 0.05) in the anti-inflammatory effect was demonstrated for the binary solid dispersion showing more than 50% decrease in the volume of carrageenan-induced tail edema compared to that of the physical mixture. Therefore, the freeze dried binary solid dispersion of meloxicam and paracetamol has shown to increase the analgesic and anti-inflammatory activities as compared to the physical mixture.