Evaluation of Tableting and Tablet Properties of Kollidon SR: The Influence of Moisture and Mixtures with Theophylline Monohydrate

Abstract

The aim of the study was firstly to investigate the influence of moisture on the tableting and tablet properties of Kollidon SR and secondly to investigate the influence of theophylline monohydrate on the tableting behavior and tablet properties produced from binary mixtures with Kollidon SR. In comparison to Kollidon SR, microcrystalline cellulose (MCC) was used. The glass transition temperature (Tg) of the powder over the whole range of RH (0-90%), and in addition, the Tg of tablets of Kollidon SR were measured. Densities and flowability of the powders were analyzed. The tablets were produced at five different maximum relative densities (rho(rel), max) on an instrumented eccentric tableting machine. They were produced at three different relative humidities (RH), 30%, 45%, and 60% RH for the pure substances and binary mixtures with different ratios of drug and excipient were tableted at 45% RH. The tableting properties were analyzed by 3D modeling, force-displacement profiles, and compactibility plots. First, the Tg of the powder decreased with increasing RH and the Tg of the tablet was 4-8 K lower than the powder. The predominant deformation of Kollidon SR is plastic deformation and Kollidon SR showed a higher compactibility than MCC. The parameters of the 3D model showed an extreme change between 45 and 60% RH, and at higher RH more and more particles deformed elastically. This was confirmed by analysis of force-displacement profiles. At 60% RH, the radial tensile strength of the Kollidon SR tablets was half of the radial tensile strength at 45% RH. The reason is a higher relative energy of plastic deformation than for MCC. This results in a better utilization of the energy to deform the powder into a tablet and the exceeding of the glass transition temperature at higher RH. In conclusion, at 60% RH at the same rho(rel, max), tableting and tablet properties of Kollidon SR are extremely changed since plasticity is significantly higher. In the second part of the study, the insufficient flowability of theophylline monohydrate can be compensated by using Kollidon SR in a mixture with up to 20% theophylline. Further, pressure plasticity e of MCC and Kollidon SR was lowered in the mixture with theophylline monohydrate. The same is valid for the compactibility. The influence of theophylline monohydrate on the pressure plasticity e of the mixtures was better compensated in the mixture with MCC than in a mixture with Kollidon SR. This compensation was also visible by analyzing the force-displacement-profiles. However, hardly any influence on the radial tensile strength could be detected. Kollidon SR and Kollidon SR mixtures exhibited a higher compactibility than MCC and MCC mixtures. The differences became smaller with increasing theophylline content.

Once-daily amoxicillin immediate- and extended-release bilayer tablets

“…Kollidon® SR is a polyvinyl acetate based excipient consisting of 80% PVAc, 19% PVP and 0.8% SLS and 0.2% silica [18,19]. It has been successfully applied for direct compression of sustained release tablets of propranolol HCl and diphenhydramine HCl [20,21] because of its good flowability.…”

Simulation Modeling of a Pharmaceutical Tablet Manufacturing Process via Wet Granulation

“…e Heckel equation is a widely studied model to calculate this relationship. A lot of research works by Picker et al [38][39][40][41][42][43][44][45][46][47][48][49] have studied the influences of pressure, compression time, and compression distance (rolling reduction) on the porosity through a promoted form of the Heckel equation:…”

“…where ε 0 is the initial porosity and K represents the change in porosity due to the rearrangement of particles in the initial state [50]. Picker et al [38][39][40][41][42][43][44][45][46][47][48][49] carried out a large number of experiments, by which we give the following models in (21)∼(23) to be identified after the analysis of each variable, and then the model parameters are calibrated with the experimental data from literature studies: e initial porosity is related to the APS of particles. Generally speaking, the initial porosity increases as the APS increases due to the gradually increasing space between the particles [50].…”

A Study on In-Line Tablet Coating—the Influence of Compaction and Coating on Tablet Dimensional Changes

“…Typical analytical methods to measure tablet dimensional changes utilize the micrometer screw gauge (10,21), thermomechanical analysis (10), or linear voltage displacement transducer (8,22). An ideal analytical technique to measure gradual tablet recovery by dimensional measurements should be contactless, continuous, and convenient.…”