Tablet Geometry Effect on the Drug Release Profile from a Hydrogel-Based Drug Delivery System

Abstract

In order to achieve the optimal level of effectiveness and safety of drugs, it is necessary to control the drug release rate. Therefore, it is important to discover the factors affecting release profile from a drug delivery system. Geometry is one of these effective factors for a tablet-shaped drug delivery system. In this study, an attempt has been made to answer a general question of how the geometry of a tablet can affect the drug release profile. For this purpose, the drug release process of theophylline from two hundred HPMC-based tablets, which are categorized into eight groups of common geometries in the production of oral tablets, was simulated using finite element analysis. The analysis of the results of these simulations was carried out using statistical methods including partial least squares regression and ANOVA tests. The results showed that it is possible to predict the drug release profile by knowing the geometry type and dimensions of a tablet without performing numerous dissolution tests. Another result was that, although in many previous studies the difference in the drug release profile from several tablets with different geometries was interpreted only by variables related to the surface, the results showed that regardless of the type of geometry and its dimensions, it is not possible to have an accurate prediction of the drug release profile. Also, the results showed that without any change in the dose of the drug and the ingredients of the tablet and only because of the difference in geometry type, the tablets significantly differ in release profile. This occurred in such a way that, for example, the release time of the entire drug mass from two tablets with the same mass and materials but different geometries can be different by about seven times.

Keywords: AUC; DE; HPMC; MDT; QbD; drug delivery; geometry; hydrogel; mathematical modeling; release profile.

Figure 1

Cylindrical geometry used in the model.

Figure 2

Cross-section and boundaries used in the model [24].

Figure 3

Polymer flux on the surface element at the erosion front [24].

Figure 4

Percentage of the drug released and the polymer eroded during the time while rotating the paddle at a speed of (a) 50 rpm, (b) 75 rpm, (c) 100 rpm. Drug released, Sim: the percentage of drug released obtained from the simulation, Drug released, Exp: the percentage of drug released obtained from the experimental results, Polymer eroded, Sim: the percentage of polymer eroded obtained from the simulation, Polymer eroded, Exp: the percentage of polymer eroded obtained from the experimental results [40].

Figure 5

(a) Percentage of the drug released and polymer eroded during the time and (b) maximum radius and half-thickness of tablet during the time. Drug release, Exp: the percentage of drug released obtained from the experimental results, Drug release, Sim: the percentage of drug released obtained from the simulation, Polymer eroded, Sim: the percentage of polymer eroded obtained from the experimental results, Polymer eroded, Exp: the percentage of polymer eroded obtained from the simulation, Semi thickness, Sim: semi-thickness of tablet obtained from the simulation, Semi thickness, Exp: semi-thickness of tablet obtained from the experimental results, Radius, Sim: radius of tablet obtained from the simulation, Radius, Exp: radius of tablet obtained from the experimental results [25].

Figure 6

Drug mass fraction and matrix shape change in (a) SHC, (b) STC, (c) DC, (d) EXDC, (e) FF, (f) FFBE, (g) CR, (h) TO geometries, before the start of the dissolution process (upper figures) and 6 h from the start of the dissolution process (lower figures).

Figure 7

Common features of tablets. (a) Perspective, (b) maximum length and maximum width, (c) maximum height.

Figure 8

(a) Cumulative percentage of the drug released, (b) percentage of the drug released at each moment, (c) surface-to-volume ratio during the time for tablet #1 (orange line) and tablet #2 (blue line).

Figure 9

Comparison of average (a) 95 rel response (the time required to release 95% of the initial mass of the drug) and (b) 30 min response (percentage of drug released after 30 min from the starting moment of the dissolution process) for the 8 investigated geometries.