Solubility enhancement of some poorly soluble drugs by solid dispersion using Ziziphus spina-christi gum polymer

• Published in: Saudi pharmaceutical journal Vol. 30; no. 6; pp. 711 - 725
• Main Authors: Alwossabi, Ameen M., Elamin, Eltayeb S., Ahmed, Elhadi M.M., Abdelrahman, Mohammed
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.06.2022; Elsevier
• Subjects: Modification of polymer; Natural polymer; Original; Poorly water-soluble drugs; Solid dispersion; Ziziphus gum polymer; Ziziphus spina-christi; Solid dispersion; Ziziphus spina-christi; Poorly water-soluble drugs; Modification of polymer; Ziziphus gum polymer; Natural polymer
• ISSN: 1319-0164; 2213-7475
• DOI: 10.1016/j.jsps.2022.04.002

A high percentage of marketed drugs suffer from poor water solubility and require an appropriate technique to increase their solubility. This study aims to compare physically modified and unmodified gum polymers extracted from Ziziphus spina-christi fruits as solid dispersion carriers for some drugs. Taguchi Orthogonal Design (L9) was chosen for the screening and optimization of the solid dispersions. The design has four factors: type of drug, type of polymer, type of solid dispersion process, and drug to polymer ratio. Each factor was varied in three stages and the total number of runs was 9 in triplicate. The polymer was physically modified by heating (M1ZG) or freeze-drying (M2ZG). The drugs were selected according to the biopharmaceutical classification system, namely loratadine and glimepiride (class II) and furosemide (class IV). Drugs were dispersed in the polymer in three different ratios 1: 1, 1: 2, and 1: 3. Solid dispersions were made by co-grinding, solvent evaporation, and kneading methods. Modified and unmodified polymers were characterized in terms of their organoleptic properties, solubility, powder flowability, density, viscosity, swelling index, and water retention capacity. Solid dispersions were characterized in terms of percentage practical yield, solubility improvement, and drug compatibility. The results showed that the organoleptic properties of polymers were not changed by the gum modification. The swelling index of the polymer was doubled in M1ZG. The viscosity and water retention capacity of the polymer was increased in both modified polymers. All solid dispersions showed a high practical percentage yield of more than 93%, the higher values ​​being more associated with loratadine and furosemide than with glimepiride. The improvement in solubility was observed in all solid dispersions prepared, the values ​​varying with the pH of the medium and the method of modification. The FTIR results indicated that there was no chemical interaction between these drugs and the polymer used. Analysis of the results according to the Taguchi orthogonal design indicated 51 folds aqueous solubility enhancement for loratadine using M2ZG polymer at a ratio of 1: 3 of Drug: polymer. This study showed the possibility of improving the solubility of other poorly soluble drugs.