Development of composite particles of rice starch and microcrystalline cellulose as direct compression diluent

Abstract

Composite particles of rice grains and microcrystalline cellulose (MCC) were fabricated via spray drying technique for the use as directly compressible excipient. Grains from rice starch (RS, native starch with low protein content) and rice flour (RF, starch without treatment of protein extraction) were employed to form composite particles with various proportions of MCC of two different size ranges. The different size ranges of MCC were prepared by sieving through 45 µm aperture screen (VS) and by size reduction using jet mill (VJM). The composite particles obtained were evaluated for the powder characteristics and tabletting properties. Powder characteristics with respect to percent loss on drying (LOD), angle of repose, bulk and packed density, percent compressibility were determined and used to calculate flowability index, which would indicate the degree of fluidity of powders. It was found that an increase in MCC quantity markedly increased compressibility but decrease flowability index. Combination of RS and MCC gave higher compressibility than that of RF and MCC. Although the hardness of compacts prepared from composite particles containing VS or VJM were not different, composite particles using VJM produced aggregate powder in spherical form. From DSC thermograms of spray-dried powders of RS and MCC formulations, surface gelatinization of starch grain seemed increasing as MCC content in the formulation was increased. RS and VJM at the ratio of 7 : 3 (RS/MCC), which provided suitable physical properties of powder and reasonable price of production, was chosen for the investigation of processing conditions of spray drying. Processing variables such as feed suspension concentration, feed rate, inlet temperature, and atomizing pressure also affected the powder and tabletting properties of the obtained composite particles. Production of RS/MCC could be scaled up and reproduced with the consistent powder and tabletting properties. An application of the composite particles of RS and MCC (7 : 3) in the manufacture of tablet products in comparison with commercial directly compressible vehicles (Vivapur®, Eratab®, Tablettose®, and Cellactose®) was performed. Like other diluents, magnesium stearate exerted the negative effect on the compressibility of RS/MCC. RS/MCC possessed compressibility and dilution potential greater than that of Eratab®, Tablettose®, and Cellactose® but lower than that of Vivapur®. Model drug formulations for direct compression tablets using isoniazid as a representative of soluble drug and hydrochlorothiazide as a representative of very slightly soluble drug were evaluated. Tablets produced from both drugs using composite particles as directly compressible diluent possessed fast disintegration time and complete dissolution as complied with USP 24 specifications. Volume reduction mechanisms of composite particles using Heckel analysis revealed lower fragmentation at low compression force but higher plastic deformation than that of lactose-based diluents.