With the introduction of instrumented single and multistation tablet presses, directly compressible materials have gained increasing importance in tablet formulations. Materials comprising individual unmodified particles are not often suitable as filler–binders because of their lack of flowability (e.g., native starches), lack of binding properties (e.g. α lactose monohydrate 100#), and lubricant sensitivity (e.g., native starches). Although binding properties can be improved with physical modifications such as dehydration, partial pregelatinization, and coating, the flow properties of these products are often still insufficient (1). Coprocessed multicomponent-based excipients help achieve better powder characteristics and tableting properties than when a single substance or a physical mixture is used (2), and several coprocessed filler–binders have appeared in the pharmaceutical market in recent years.
This study evaluated six binders: the traditional binders hydroxypropyl methylcellulose (HPMC), guar gum, acacia, and polyethylene glycol (PEG); colloidal silicon dioxide, which has been reported to increase the hardness of the tablets (3); and starch, which exhibits both binding and disintegrant properties when it is incorporated either as a paste or dry before granulation with other agents. Wet granulation was used because of its simplicity.
Several studies have reported the influence of individual binders on the tensile strength of tablets (4–9). Very few studies have actually combined more than one binder in a single formulation and evaluated their influence on tensile strength (10). In this study, the Plackett-Burman statistical design was used to screen the factors affecting a certain attribute (11–14). These variables were optimized to achieve the desirable response after initial screening (15). Various combinations of the six binders were used according to the Plackett-Burman design to prepare a directly compressible adjuvant.
Lactose, dibasic calcium phosphate dihydrate (DCP), starch, PEG, and HPMC 15 cps were received as generous gifts from Bombay Tablets (Gandhinagar, India). Acacia, guar gum, magnesium stearate, and colloidal silicon dioxide were received from Torrent Research Centre (Gandhinagar, India).
Table I: Factors in the Plackett-Burman screening design.
Experimental design to prepare agglomerates
Six binders were used to prepare coprocessed directly compressible adjuvant containing lactose and DCP. Table I lists the binders used and the amount used of each. The binders were screened using a 12-run Plackett-Burman design. Table II shows the composition of each batch of agglomerates prepared using various binders as per the Plackett-Burman design. Fifty grams of lactose and 25 g of DCP were mixed. The binders were added according to the Plackett-Burman design. The whole system was mixed, and water was added as an agglomerating agent. PEG when used was dissolved in water before being added to the main bulk. The mass was forced through a 20# sieve and dried in a hot air oven at 80 ° C. The dried agglomerates were sifted through a 40# sieve. The agglomerates of 40–200# were collected and stored in an airtight container until further use.
Table II: Formulation of various batches of agglomerates using a Plackett-Burman design and results of evaluation parameters.