Quantification of Moisture-Induced Cohesion in Pharmaceutical Mixtures

Abstract

Moisture-induced flow variabilities in pharmaceutical blends lead to multiple impediments during manufacturing of solid dosage formulations. Processing and storage humidity conditions both govern the moisture contents of the pharmaceutical mixtures and bear significant impact on the final product quality. In this study, experimentally validated discrete element method-based computational models along with statistical formalism have been implemented to develop a predictive tool for moisture-induced cohesion in binary and tertiary mixtures. V-blending was applied to prepare the pharmaceutical blends, and mixing characterization was performed using a Raman PhAT probe. Optimum fill volume was established for the mixing conditions to minimize static charging due to blender wall interactions on the pharmaceutical powders. A simplex-centroid (augmented) design for 3-component system was implemented to predict and quantify the nonlinear behavior of moisture-induced cohesion between the pharmaceutical powders based on their systematic hopper discharge studies (experiments and simulations). A methodical implementation of these quantification tools was hence performed to validate a design space that enables an approach to the appropriate selection of blend concentrations that achieve minimum mixture flow variability across different humidity conditions.

Recent Applications of Mixture Designs in Beverages, Foods, and Pharmaceutical Health: A Systematic Review and Meta-Analysis

“…Used to improve solubility of poorly soluble drugs [142]; medicated chewing gums [120]; bioactive dressings [128]; or tablets [121,139], oleogels [144,145], organogels for cardiovascular diseases [118], nanoparticles with amoxicillin trihydrate and thymol [131,134], novel excipients [129,136,146] and oils mixture with salicylic acid for ointment [143] formulation; itraconazole for oral [27,127], gel with loratadine [148], tablets of metformin [130], controlled release of ketoprofen [23] and excipients with finasteride [126] formulation; emulsion formulation of vitamins [119], of aceclofenac [122], of raloxifen [135], of aprepitant [123], of catechin [28], of darunavir [117], of lopinavir [116], of butenafine hydrochloride [132], of cathepsin K inhibitor [140], of telmisartan [138], of olmesartan medoxomil [137], of bovine serum albumin [141], of nelfinavir mesylate [124], of docetaxel [125], of nutraceutical products [147] and oxidative stability avocado oil [133].…”

DEM based investigation of powder packing in 3D printing of pharmaceutical tablets

“…Three formulations as mentioned in Table 1 were prepared by mixing in a lab scale V-blender for 18 minutes at 29 RPM at 40% fill volume. The mixing regimen of the study was maintained such that the gravitational forces were higher than the centrifugal forces as optimized by previous studies from our group [4,8].…”

Influence of Relative Humidity on Interparticle Capillary Adhesion

“…3 One inevitable consequence is the increase in interparticle adhesion in the presence of moisture, resulting in powder aggregation and coagulation. It is therefore crucial to investigate the influence of humidity-dependent capillary force in, for instance, food processing, 4 pharmaceutical mixtures, 5 powder handling, 6 aerosol suspension, 7 and biomaterial dehydration. 8 Such studies are in fact fundamental to estimate the performance and lifespan of micro-/nano-electromechanical devices and nanostructures.…”