Lubricant Sensitivity of Direct Compression Grades of Lactose in Continuous and Batch Tableting Process.

Modern pharmaceutical manufacturing based on Quality by Design and digitalisation is revolutionising the pharmaceutical industry. Continuous processes are promoted as they increase efficiency and improve quality control. Compared to batch blending, continuous blending is easier to scale and provides advantages for achieving blend homogeneity. One potential challenge of continuous blending is the risk of over-lubrication. In this study, blending homogeneity and lubricant sensitivity are investigated for both batch and continuous processes. Given their distinct chemical structures and morphologies, anhydrous lactose and granulated lactose are expected to exhibit varying sensitivities to changes in process settings across both technologies. The findings suggest that both lactose grades provide highly stable blends that can be safely utilised in both batch and continuous modes. Optimisation should focus on process variables, such as the quality of loss-in-weight feeders used for dosing low doses of ingredients. The most significant process parameter for lubricant sensitivity was the type of lactose used. Anhydrous lactose produced harder tablets than the more porous granulated lactose but was more sensitive to lubrication at the same settings. The magnesium stearate content and its interaction with the type of lactose are also critical factors, with magnesium stearate having a counterproductive impact on tabletability.

Effect of feed frame on lubricant sensitivity during upscaling from a compaction simulator to a rotary tablet press.

Internal lubrication can be associated with reduced tabletability. Deformation mechanism, lubricant type, lubricant blending time and paddle speed (PS) of the forced feeder are known to be influenceable factors. This study investigated the effect of lubricant blending time and PS of forced feeders on the tensile strength of lubricated microcrystalline cellulose (MCC) and lactose tablets. Magnesium stearate (MgSt), sodium stearyl fumarate (SSF) and stearic acid (SA) were used as lubricants. Tablets were produced on a compaction simulator and a rotary tablet press to investigate lubricant sensitivity during upscaling. Lubricant sensitivity was found higher for MCC compared to lactose which was attributed to the higher plasticity of MCC. The reduction in tensile strength upon lubricant addition followed the order: MgSt > SSF > SA; which could be linked to particle size, specific surface area and particle shape of the lubricants. Although differences in tensile strength were observed between the lubricant types, comparable ejection forces were obtained. The impact of PS on tensile strength was higher compared to lubricant blending time for both tableting machines. A good correlation of tensile strength and lubricant sensitivity between the compaction simulator and rotary tablet press was observed based on the calculation of paddle passes (NPP).

A study of a novel coprocessed dry binder composed of α-lactose monohydrate, microcrystalline cellulose and corn starch.

This paper deals with a study of the novel coprocessed dry binder Combilac®, which contains 70% of α-lactose monohydrate, 20% of microcrystalline cellulose and 10% of native corn starch. These tests include flow properties, compressibility, lubricant sensitivity, tensile strength and disintegration time of tablets. Compressibility is evaluated by means of the energy profile of compression process, test of stress relaxation and tablet strength. The above-mentioned parameters are also evaluated in the physical mixture of α-lactose monohydrate, microcrystalline cellulose and native corn starch and compared with Combilac. Combilac shows much better flowability than the physical mixture of the used dry binders. Its compressibility is better, tablets possess a higher tensile strength. Neither Combilac, nor the physical mixture can be compressed without lubricants due to high friction and sticking to the matrix. Combilac has a higher lubricant sensitivity than the physical mixture of the dry binders. Disintegration time of Combilac tablets is comparable with the disintegration time of tablets made from the physical mixture.

Vegetable-derived magnesium stearate functionality evaluation by DM(3) approach.

This study quantifies the lubricating efficiency of two grades of crystalline vegetable-derived magnesium stearate (MgSt-V) using the DM(3) approach, which utilizes design of experiments (D) and multivariate analysis techniques (M3) to evaluate the effect of a material's (M1) molecular and macroscopic properties and manufacturing factors (M2) on critical product attributes. A 2(3) factorial design (2 continuous variables plus 1 categorical factor) with three center points for each categorical factor was used to evaluate the effect of MgSt-V fraction and blend time on running powder basic flow energy (BFE), tablet mechanical strength (TMS), disintegration time (DT), and running powder lubricant sensitivity ratio (LSR). Molecular characterization of MgSt-V employed moisture sorption-desorption analysis, (13)C nuclear magnetic resonance spectroscopy, thermal analysis, and powder X-ray diffraction. MgSt-V macroscopic analysis included mean particle size, specific surface area, particle morphology, and BFE. Principal component analysis and partial least squares multivariate analysis techniques were used to develop predictive qualitative and quantitative relationships between the molecular and macroscopic properties of MgSt-V grades, design variables, and resulting tablet formulation properties. MgSt-V fraction and blending time and their square effects showed statistical significant effects. Significant variation in the molecular and macroscopic properties of MgSt-V did not have a statistically significant impact on the studied product quality attributes (BFE, TMS, DT, and LSR). In setting excipient release specifications, functional testing may be appropriate in certain cases to assess the effect of statistically significant different molecular and macroscopic properties on product quality attributes.