The effect of glidant on the tabletting behavior of common pharmaceutical excipients

Abstract

Glidant used for the purpose of powder flowability enhancement is well known within the pharmaceutical industry to improve tablet manufacturing. Despite the widespread use of glidant for this purpose, the effect of glidant on the effect of tableting behavior is not well studied. To address this deficiency, the effect on glidant on the tabletting behavior of seven common excipients was investigated. Tabletability, compressibility, compactability, and tablet expansion were studied. It was shown that glidant increased the tabletability for excipients known to exhibit plastic behavior. Based on compressibility and compactability, it was inferred that an increase in total bonding strength due to the presence of glidant was responsible for the improvement in tabletability. Results suggest this may be due to an increase in inter-particle bonding area. Conversely, glidants did not affect the tabletability of brittle excipients. The effect of glidant on die-fill bulk density was also studied to examine the impact associated with air entrapment and tablet expansion. While glidant significantly increased the die-fill powder density, this did not have an observable effect on tablet expansion or any other tabletting behavior examined.

Highlights

Glidant improved the tabletability of excipients known to exhibit plastic behavior.

Glidant increased total bonding strength thereby improving tabletability.

Glidant did not affect the tabletability of brittle excipients.

Die-fill density showed no affects related to air entrapment and tablet expansion.

Introduction

The use of colloidal silicon dioxide, also known as glidant, in pharmaceutical formulations is well studied [1]. With respect to powders and formulations potentially bound for tabletting, most studies concerned with manufacturability have focused on the use of glidant as a flowability aid [[2], [3], [4]]. The effect of glidant on the tabletting behavior of pharmaceutical powders has not been well studied. However, a few studies have reported some observations: van Veen et al. [5] reported a slight increase to the tabletability of microcrystalline cellulose (MCC) with the addition of up to 0.4% glidant and a decrease to the tabletability thereafter. Zhou et al. [6] and Chattoraj [7] reported a reduction in tabletability of MCC after adding glidant but did not control for the effect of processing. Zhou et al. [8] found that the addition of glidant improved the tabletability of ibuprofen as the glidant was able to “sink” into the surface of ibuprofen due to its “softness”. Qu et al. [9] concluded the same in their tableting experiments with ibuprofen. Apeji and Olowosulu [10] reported differences in tabletability and compressibility based on the type of glidant blended with granules of paracetamol. This author in a previous study [11] reported an increase in the tabletability of an MCC-acetominophen formulation blended with glidant. It was reasoned that the glidant caused deagglomeration of cohesive acetaminophen particles thereby increasing the inter-particle bonding area with MCC. Huang et al. [12] similarly showed an increase to the tensile strength of MCC-lactose-acetominophen blends when adding glidant. While the improved tensile strength was attributed to a facilitation in particle rearrangement under compaction pressure, the compressibility or compactability of the blends were not reported and no direct evidence given. Kunnath et al. [13] also reported an increase in the tabletability of acetaminophen with glidant attributing it to either facilitated particle rearrangement or increase in inter-particle bonding area due to deagglomeration of fine particles. No definite conclusions are given to the responsible mechanism. Kumar et al. [14] reported the observation of an optimum amount of glidant leading to increased tensile strength of a MCC-lactose blend. The results are convoluted by the complex interaction of glidant and lubricant as discussed in the study making general conclusions difficult. A study by Pingali et al. [15] focused on addition order of glidant and lubricant during blending again making any general conclusions on the effect of glidant on its own impossible.

Aside from observations of tabletability and tablet strength, glidant can potentially affect the tabletting behavior associated with air entrapment. Air entrapment has been identified as a possible factor in causing tabletting defects such as cracking, lamination, or capping [[16], [17], [18], [19], [20]]. Since glidants are well known to increase bulk density of pharmaceutical powders [[21], [22], [23], [24]], the volume of air present in a powder can be reduced which may diminish the adverse effects of air entrapment. The author knows of no studies that have specifically investigated the effects of glidant on the tabletting behavior associated with air entrapment.

Overall, there is a lack of data focused on the effect of glidant on the tabletting behavior of pharmaceutical powders. Most observations are found in studies not primarily designed to elucidate the effect of glidant on tabletting. Given the fact that many studies recommend the use of glidants to enhance the manufacturability of pharmaceutical powders, and in fact the use of glidant is a very common industry practice for this purpose, additional study is warranted. Accordingly, this study begins this task by investigating the effect of glidant on the tabletting behavior of seven pharmaceutical excipients commonly used in tabletting. Tabletability, compressibility, compactability, and tablet expansion were measured using a compaction simulator press at compaction speeds and pressures relevant to manufacturing. Bulk density of the powders was also scrutinized to evaluate the effect on air entrapment.

Materials

Seven excipients common to pharmaceutical tableting were studied as detailed in Table 1. Microcrystalline cellulose (Avicel PH 102) was purchased from DuPont, USA. Copovidone (Kollidon VA 64) was purchased from BASF, Germany. Dicalcium phosphate (DCP, DI-CAFOS A 60) was purchased from Budenheim, Germany. Hydroxypropylmethylcellulose (HPMC, Methocel K4M) was purchased from Dow Chemical Company, USA. Lactose (316 NF Fast Flo) was purchased from Foremost Farms, USA. Mannitol (Pearlitol 100 SD) was

Maxx Capece, Mark Czyzewski, The effect of glidant on the tabletting behavior of common pharmaceutical excipients,
Powder Technology, 2024, 119908, ISSN 0032-5910, https://doi.org/10.1016/j.powtec.2024.119908.