Tablets are frequently used solid oral dosage forms. Besides the identity, purity and content of the active pharmaceutical ingredient (API), several properties of the dosage form are important quality attributes. These include mechanical strength, API dissolution and disintegration. The mentioned properties are influenced by the excipients as well as the manufacturing process. The manufacturing process, in turn, must be suitable for the API, the excipients, the aimed product and its properties.

To ensure enough mechanical strength, binders are added to the tablet formulation. A variety of binders is available on the market including cellulose derivatives like hydroxypropyl cellulose (HPC) or hydroxypropyl methylcellulose or polymers based on vinyl pyrrolidone.

For API dissolution, disintegration can be an essential step. For this purpose, disintegrants are applied. Some disintegrants, called superdisintegrants, are polymers, which are highly effective and lead to tablet disintegration already in concentrations between one and four percent [1]. Croscarmellose sodium (xCMC), sodium starch glycolate (SSG) and crospovidone (xPVP) are the most frequently mentioned superdisintegrants. Their commonality is a crosslinking between the polymer chains, which reduces or overrides the solubility in water and decreases the viscosity [2], [3].

Most studies investigate the disintegration of direct compressed tablets to reduce effects caused by granulation [4], [5]. However, granulation is a common step in pharmaceutical manufacturing. It is used to reduce powder-induced problems like poor flow properties caused by a large surface and low weight, formation of dust or segregation [6], [7]. Even if some studies applying wet granulation with intra- and extragranular disintegrants were performed, not all wet granulation techniques are covered. Different granulation techniques result in different granule and tablet properties and therefore results from all wet granulation techniques are necessary [5], [8], [9], [10].

Although some studies regarding disintegrants were made, the influence of the localization and formulation is not fully understood yet [11]. Several factors are described as relevant for the disintegrant effectiveness, e.g. filler, binder or granulation technique [12], [13], [14]. Rojas et al. determined the filler as more influential than the disintegrant for the disintegration in some cases [15]. Gupta et al. describe all formulation ingredients as influential but filler and disintegrant are stated as most important [16]. Regarding the manufacturing, dry and wet granulation reduce the disintegrant efficacy [12]. Obviously, the disintegrant concentration has a significant effect on the disintegration, but also on the API dissolution and mechanical strength of the tablet [17].

However, also the disintegration mechanism is not clear yet. Various reviews discuss the different mechanisms [18], [19], [20] whereby swelling, wicking and shape recovery are the most frequently mentioned ones.

Swelling, often described as mechanism for tablet disintegration [15], [21], [22], [23], [24], [25], is an omnidirectional enlargement of the particle or tablet caused by water contact [24]. Water as a plasticizer penetrates between the disintegrant polymerchains, unravels them and leads to disintegrant particle enlargement. However, constant particle enlargement might press out water of the porous tablet system [22]. Swelling is described as main disintegration mechanism of xCMC and SSG [15], [22], [23], [24], [25]. In some literature swelling it is also mentioned for xPVP [26], [27].

Wicking is a capillary force-induced flow of a liquid into a porous structure where the fiber-air interface is changed to a fiber-liquid interface [28], [29]. However, wicking might ease water intrusion and soften the tablet instead of causing tablet disintegration [5].

The third mentioned mechanism, shape or strain recovery, is a unidirectional deformation process, where disintegrant particles are activated by water contact and alter their deformation in the opposite direction of compression [23]. The enlargement of disintegrant particles is confined and therefore water will not be pressed out of the porous tablet system but will penetrate until all pores are filled [22]. However, a minimum level of energy must be brought into the tablet during compression to enable disintegration by shape recovery [30]. Shape recovery is described as main disintegration mechanism of xPVP [22], [23], [31] but was sometimes also mentioned in the case of xCMC [24].

This study aimed to find the optimal superdisintegrant type and localization in tablets which are manufactured with HPC as binder and lactose as filler. Because of the lack of scientific knowledge about the influence of wet granulation on the disintegration, it should examine the properties of tablets produced with granules resulting from a wet granulation process. Beside the disintegrant type, the location of the disintegrant (intragranular, split or extragranular) is investigated.