Development of a multi-functional rice starch-based pharmaceutical excipient by co-process technique for direct compression of tablets

Abstract

The advancement in tablet production such unique dosage forms and tableting technology contribute the development of new excipient to support tablet production with specific conditions. Co-processed rice starches are developed as multifunctional excipients to support these purposes for direct compression (DC) of tablets, which is the simplest and most economical method for tablet production The co-process technique is applied to develop the co-processed rice starch using physical medication to improve functionality or eradicate undesirable properties of materials. This technique alters particulate characteristics of material without involving chemical structure and stability. The co-processed rice starches (CSs) are generated from various excipients including native rice starch (RS), cross-linked carboxymethy1 rich starch (CCMS), and silicon dioxide (in a liquid form of sodium silicate solution) through spray drying technique, that has been reported to promote material flowability. The effects of spray drying conditions (nozzle tip sizes and solid contents) and excipient ratios are investigated. At 2.7 mm of spray dry nozzle tip with 40% solid content, the CSs particles exhibit the largest particle size with an agglomerate spherical shape that promotes material flowability, making this condition the most optimal for spray drying. This spray drying condition is applied to produced CSs with various excipient ratios (10-15% of CCMS and 0.5-6.75% of silicon dioxide). The CSs particles show improvement in swellability, flowability, compressibility, and disintegration property. The FT-IR spectra confirm that only physical modification is involved in the co-process step. The XRD patterns reveal that silicification increases amorphous regions, especially at high silicification levels, that promote solubility of CSs. On the other hand, CCMS co-process improves material swellability. The C'Ss illustrate agglomerate spherical particles (24.33 - 27.03 um) under SEM microscope with narrow unimodal distribution, while other DC commercial excipients (silicified microcrystalline cellulose (PROSOLV® SMCC) and spray-dried lactose (Tablettose®)) show a wide distribution of particle size. The pharmaceutical property studies reveal that CS-3 (RS co-processed with 10% of CCMS and 2.70% of silicon dioxide) exhibits the best pharmaceutical characteristics. Its flowability is comparable to the DC commercial excipients, which are superior to RS and physical mixture. The compressibility of CS-3 falls in between PROSOLV® SMCC (highly plastic material) and Tablettose® (brittle material) as starch commonly exhibits plasticity during compaction. The increase of amorphous region facilitates plastic deformation property of CS, while promoting the disintegration property of CS-3 (28 s) which is faster than that of PROSOLV® SMCC, and comparable to Tablettose *. Furthermore, the presence of silicon dioxide on CS-3 mitigates the lubricant's negative effect on tensile strength reduction and disintegration time. Therefore, CS-3 could potentially be applied as a multifunctional excipient for DC.

The lubricant co-processed, rice starch-based excipient (CSL), which is derived from CS-3, has been developed to broaden the applications as a ready-to- use excipient. Three different types of 1ubricants (glycery1 monostearate (GM), stearic acid (S.A), and sodium steary1 fumarate (SF)) are co-processed in the range of 0.5 - 3.0%, then the lubricant co-processed excipients are evaluated. The CSLs show agglomerate spherical particles, while 1ubricant particles are melted and covered on the particle surface owing to high spray drying temperature. The incorporation of lubricant improves material flowability that is remarkable observed at high SF levels. The hydrophobicity of lubricant adversely affects compressibility and disintegration property. The co-process with SF has the lowest effect on tensile strength reduction, whereas lubrication time slightly affects tablet tensile strength as CSLs are self-1ubricant materials. Disintegration time of CSLs elevates with 1ubricant concentrations, while SA exhibits the lowest impact on disintegration time compared to other lubricants. Among CSLs, CSSF-3 exhibits the most desirable properties that show superior properties to the physical mixture in terms of flowability, disintegration property, and effect of 1ubrication. Moreover, there is no significant difference between the compressibility of CSSF-3 and the physical mixture.

The formulation study reveals that CS-3 can be incorporated with paracetamol (poor flow and compressibility API) up to 40% of the API in the formulation. The CS-3 formulation shows satisfactory tablet properties produced with the DC method. On the other hand. CSSF-3 is suitable for a low drug-loaded formulation, which shows more uniformity than the physical mixture. When compared to the commercial DC excipient formulations and the physical mixtures, the CS and CSL exhibit faster and higher drug release. For these reasons, CS and CSL could fulfil1 the requirements of multifunctional excipient for DC.