Tablets Made from Paper-An Industrially Feasible Approach

Abstract

Many orally administrated drugs exhibit poor bioavailability due to their limited solubility. The smartFilm technology is an innovative approach to improve the drug aqueous solubility, where the drug is embedded within the matrix of cellulose-based paper in an amorphous state, hence increasing its solubility. Despite its proven effectiveness, smartFilms, i.e., pieces of paper, exhibit limited flowability and are not easy to swallow, and thus oral administration is not convenient. In addition, there is a lack of knowledge of their mechanical behavior under compression. This study aimed to transform unloaded smartFilms, i.e., paper, into a flowable physical form and investigated its mechanical behavior when compressed. Granules made of paper were prepared via wet granulation and were compressed into tablets. The influence of using different amounts and forms of sucrose, as a binder, on the pharmaceutical properties of the produced granules and tablets was studied and the most suitable composition was identified by using instrumented die experiments. For this, the Poisson's ratio and Young's modulus were determined for different compaction force levels and the deformation behavior was estimated with the Heckel mathematical model. All granule batches showed good flowability with angle of repose values between 25-35°. Granule batches with ≤30% dry sucrose content produced tablets that fulfilled the European Pharmacopeia requirements, and the compaction behavior of the granules was found to be comparable to the behavior of classical binders and compression enhancers. Paper can be transferred into granules. These granules can be used as suitable intermediate products for the production of tablets made of paper in large, industrial scale.

Keywords: granules; instrumented die compression; mechanical modeling; oral drug delivery; paper; tablet manufacturing.

Figure 1

Numeric particle size distribution of paper granules from different batches based on the predetermined Feret’s diameter. A d(n) 0.5 represents the size where 50% of all granules are smaller or equal to the given number.

Figure 2

Paper granules with 20% sucrose content (B3) and the produced tablet made from the B3 paper granules.

Figure 3

Experimental results of the instrumented die compression test of granules batches B1, B3 and B6. Strain rate dependency in logarithmic scale axial stress—axial true strain (a), friction coefficient—mean punch force (b), typical loading-unloading curves of granules compaction process indicating the influence of the sucrose content on axial stress—axial true strain (c) and radial stress—axial true strain (d) at 0.1 mm/s velocity.

Figure 4

Poisson’s ratio and Young’s modulus of granule batches B1, B3, B6 at different compaction force levels. Poisson’s ratio—axial true strain (a); Young’s modulus—axial true strain (b); Poisson’s ratio—porosity (c); Young’s modulus—porosity (d).

Figure 5

Heckel plots calculated for the three batches and linear regression fit to determine the yield Pressure (P_y). Coefficient of determination for the fits are: R² =0.999 for B1, R² = 0.9999 for B3 and R² = 0.9989 for B6.