Mechanical Properties and Powder Rheology of Conventional and Innovative Excipients for Food Supplements in Solid Form

Abstract

The growing regulatory scrutiny and the emerging trends towards natural products and clean labels have led to a particular focus on food supplements’ composition, including excipients. The objective of this study is to establish a methodological approach combining conventional techniques, i.e., tapped density and flowability testers, with more objective and quantitative ones to identify alternative powder excipients that can replace conventional ones in the development of solid-dose formulations without affecting their processing, workability, and mechanical properties. In the first phase, the alternative powder excipients were characterized in terms of cohesiveness, compressibility, and flow function coefficient. We then evaluated the possibility of using selected excipient combinations to totally and/or partially replace the conventional excipients within three nutraceutical formulations. Glyceryl behenate at 1–3% w/w could be considered as a viable alternative lubricant to magnesium stearate without compromising the rheological properties of the mixtures. Fructo-oligosaccharides showed a free-flowing behavior comparable to calcium phosphate and microcrystalline cellulose, improving the flowability and compressibility of the formulations. The study of powder rheology could be advantageous to formulate new products or reformulate existing ones in a time- and money-saving way, leading to high-quality products that can appeal to consumers in terms of health-functional effectiveness.

1. Introduction

A significant number of pharmaceutical formulations and food supplements are presented in solid dosage form for oral use. Tablets and capsules are the preferred choices for both consumers, owing to their ease of administration, and manufacturers, due to their relative simplicity in production and their ability to ensure product stability, precise dosing, and controlled release kinetics [1]. Excipients play a crucial role in overcoming these challenges and optimizing the performance of solid dosage forms. A rational choice of excipients is essential to ensure adequate technological properties, such as powder flowability, processability, compressibility, and mechanical strength of the product, while also influencing the stability, bioavailability, and release profile of the active ingredient [2,3]. Moreover, excipients contribute to the overall product quality, impacting factors such as taste and ease of administration. According to their functionality, excipients for oral solid formulations can be divided into different categories. Common diluents and fillers include microcrystalline cellulose [4,5], calcium phosphates [6,7], and polyols such as mannitol or isomalt [8,9,10]. Binders are often based on cellulosic derivatives or synthetic polymers such as polyvinylpyrrolidone. Disintegrants include starches and super-disintegrants such as sodium croscarmellose [11], whereas hydroxypropyl methylcellulose is widely used for sustained-release matrices [12]. Lubricants and glidants are essential, such as magnesium stearate [13] and silicon dioxide [14]. Ancillary excipients such as sweeteners, flavors, colorants, and pH adjusters [15,16] complete the formulation when needed.

The nutritional supplement industry is experiencing rapid growth, driven by the increasing consumer interest in health and wellness [17]. Moreover, the growing emphasis on naturalness, clean labels, and sustainability [18,19] is forcing this industry to seek innovative approaches to product design and formulation that meet consumers’ expectations while adhering to stringent regulatory guidelines. Balancing regulatory compliance with product differentiation is essential for success in this industry. The focus on safety rather than efficacy, combined with diverse distribution channels, allows for greater flexibility and offers more opportunities for new product development compared to pharmaceuticals [20].

This study aimed to develop a methodological framework integrating conventional powder-characterization methods (e.g., flowability and tapped-density measurements) with advanced rheological analysis using a powder shear cell. This approach supports the incorporation of new functional excipients with enhanced health benefits, such as glyceryl behenate, tapioca maltodextrin, carob gum, oligosaccharides, and arabinogalactans, replacing traditional ones, without compromising the mechanical properties and technological performance of nutraceutical products.

Glyceryl behenate is based on a mix of glycerol esters of behenic acid and is commonly used in film coating and sustained drug release matrix [21,22]. It is also reported as an alternative lubricant to the conventional magnesium stearate without a significant impact on tablet strength and manufacturing [23,24]. Maltodextrins are obtained from acidic or enzymatic hydrolysis of corn starch. They are used extensively in the food industry as stabilizers, as well as binders and diluents in pharmaceutical applications [25]. The tapioca maltodextrin employed in this study presents a low dextrose equivalent (DE) value, suggesting a favorable effect of this ingredient on glycemic impact. Carob gum is a galactomannan obtained from the seeds of the carob tree (Ceratonia siliqua L.) and is commonly employed as a thickening and stabilizing agent in the food industry [26]. Carob gum is also reported as a viscous, soluble dietary fiber, suitable as a supplement for weight control and the management of glucose and lipid metabolism [27,28]. Fructo-oligosaccharides and galacto-oligosaccharides (FOS and GOS) are non-digestible oligosaccharides that are composed of a small number (2–60) of fructose and galactose units, respectively. They are usually included as active ingredients in food supplements and functional foods thanks to their prebiotic activity [29,30,31,32,33,34]. Besides their healthy positive effect and low glycemic index, GOS and FOS present some interesting technical advantages, such as very good palatability, high flowability, and solubility [35]. Larch arabinogalactan is a highly branched, non-starch hemicellulose polysaccharide made from galactose and arabinose units that may compose up to 35% of the dry wood of the larch tree [36,37,38]. It is proposed as an active ingredient in food supplements for the wide range of biological properties, such as protection of gastrointestinal mucosa, prebiotic effect, and enhancement of immune function [39,40].

In the reformulation of existing nutraceutical products with alternative excipients, the preservation of the processability of powder mixtures, including powders’ flowability, density, and compressibility, must be considered. These properties are influenced by a large variety of different parameters, some intrinsic to powders, such as size, shape, surface roughness, and electrical charge, and others due to external environmental conditions, such as temperature, relative air humidity, pressure, moisture content, and consolidation state [41,42]. The flow properties of powders represent a critical factor to consider during the industrial processes: their measurement allows for predicting the powders’ behavior in the development phases, including handling, pouring, and compression. Poor flowability can result in issues such as uneven mixing, equipment blockages, and packaging difficulties, which also affect the quality and consistency of the final product [43].

Different instrumental techniques are employed to assess powder flow properties during the research and development stage. Traditional methods, including flowability testing, such as the measurement of the angle of repose, and the use of tapped density testers, which allow the determination of Carr’s and Hausner’s indices, offer rapid, cost-effective results. However, these methods provide only qualitative insights and are prone to operator variability and a lack of reproducibility [44,45]. In contrast, rheological measurements involving the use of shear and flow cells provide more objective and reproducible quantitative data, characterizing powder flow and cohesive properties through scientifically rigorous parameters [46]. Shear cell tests, a technique introduced by A. W. Jenike to assess hopper and bin design parameters for gravity-fed materials, are a widely used method for characterizing powder flow properties [47]. This technique provides critical insights into fundamental solid properties, including cohesion, unconfined yield strength, angle of internal friction, compressibility, and wall friction. Shear cell analysis is particularly effective for characterizing powder flowability under varying consolidation states, using the material flow function and the flow coefficient (ffc) [48,49,50,51]. However, it may be less sensitive to subtle changes in free-flowing powders that could affect process performance. Furthermore, commercial shear cell instruments can face limitations when handling larger particle sizes typical of granular materials or small quantities of loosely compacted powders. This is especially challenging in fields such as pharmaceuticals, where obtaining sufficient material for testing can be difficult [52,53].

In this work, through practical case studies, we illustrate how the aforementioned instrumental techniques can be applied to characterize and compare excipients and to optimize solid dosage formulations. Nutraceutical ingredients with well-known health-promoting effects, also characterized by potential technical features (e.g., FOS, GOS, larch arabinogalactans, glyceryl behenate, tapioca maltodextrin, and carob gum), were employed as alternative excipients for the production of food supplements in solid forms to create innovative, healthy, and functional vehicles with comparable technical performance to conventional excipients. While many conventional excipients used in solid dosage forms (e.g., microcrystalline cellulose) are plant-derived, the clean-label trend is also influenced by the perception of minimal processing and the presence of additional functional or health-related properties. For this reason, these alternative excipients are increasingly attractive, as they combine natural origin with specific technological and physiological functions that align with current consumer expectations. The alternative excipients were compared with conventional diluents and lubricants commonly used in the nutraceutical industry, considering different analytical and instrumental approaches, such as flow function, wall friction, compressibility, and flowability. Once the most appropriate alternative excipients had been identified, combinations of excipients at specific concentrations and ratios were employed to reformulate three existing food supplements to verify that the technological and flow properties remained unchanged.

2. Materials and Methods

2.1. Materials

In

Table 1. Particle size (µm) of each ingredient employed for conventional and alternative powder mixture formulation.

Code	Ingredient	Supplier	Function	Particle Size
MC	Microcrystalline cellulose	Roquette (Lestrem, France)	Conventional excipient	Residue on 250 µm (8% max) Residue on 75 µm (45% min) Residue less than 5 µm (10% max)
M	Mannitol	Roquette (Lestrem, France)	Conventional excipient	>500 µm (10% max) >315 µm (25% max) >40 µm (60% min)
CMC	Carboxymethyl cellulose	Roquette (Lestrem, France)	Conventional excipient	Retained on 75 µm (10% max)
CP	Dicalcium phosphate 2-hydrate	Budenheim, (Budenheim, Germany)	Conventional excipient	<45 µm (5%) >150 µm (40–80%) >425 µm (1%)
I	Isomalt	Beneo (Mannhein, Germany)	Conventional excipient	>500 µm max 5% >250 µm 20–70% <63 µm max 15%
HPC	Hydroxypropylcellulose	Ashland Industries (Milano, Italy)	Conventional excipient	Through 149 µm (75%) Through 177 µm (90%) Through 250 µm (99.5%)
MS	Magnesium stearate	Peter Greven (Euskirchen, Germany)	Conventional lubricant	Sieve residue at 74 µm (1%)
S1	Silicon dioxide	WR Grace & Co. (Columbia, MD, USA).	Conventional excipient	2–4.5 µm
S2	Silicon dioxide	Evonik (Hanau-Wolfgang, Germany)	Conventional excipient	320 µm (75%)
FOS	FOS	Cosucra (Pecq, Belgium)	Alternative excipient	<500 µm
GOS	GOS	NFBC (Yunfu city, Guangdong Province, China)	Alternative excipient	<500 µm
AG	Larch arabinogalactans	Lonza (Basel, Switzerland).	Alternative excipient	Not more than 20% through 420 µm
MD	Tapioca maltodextrins	Ingredion (Manchester, UK)	Alternative excipient	<500 µm
LBG	Carob gum	Faravelli SpA (Milano, Italy).	Alternative excipient	<500 µm
GB	Glyceril dibehenate	Gattefossè (Saint-Priest Cedex, France)	Alternative lubricant	50 µm (average value)
	Lipophilic vitamin	BASF (Ludwigshafen am Rhein, Germany).	Active (product 1)	100% through 841 µm ≥90% through 420 µm ≤15% through 149 µm
	Hydrophilic vitamin	Vivatis Pharma Italia (Varese, Italy).	Active (product 2)	≥95% through 177 µm
	Botanical dry extract complex from Quebracho and Chestnut	Silvachimica srl (Cuneo, Italy).	Active (product 3)	Min. 90% through 125 µm

, the ingredients used in this work are reported, with the values of particle size declared by the suppliers in the technical data sheet. The selection of alternative excipients was based on technological suitability (as diluents, binders, or glidants), natural origin, safety considerations, functional and health-related properties, and economic feasibility. Almost all excipients employed were food-grade ingredients in compliance with the requirements established by Codex Alimentarius, Food Chemicals Codex (FCC) and Regulation (EU) No 231/2012, except for carboxymethyl cellulose and mannitol, which are pharmaceutical grade ingredients, in compliance with the current monographs in the European (Ph.Eur.), US (USP-NF) and British (BP) pharmacopeias.

2.2. Flowability Test

The tests were conducted using the Powder Flowability Tester BEP2 (Copley Scientific, Nottingham, UK), a funnel with three quick-change stainless-steel nozzles of different diameters (25 mm, 15 mm, and 10 mm). The test was performed under standard laboratory conditions (20–25 °C; 40–60% relative humidity). 100 g of the sample under examination was poured into the funnel kept vertical by a special support and without compacting, while the opening at the base was appropriately blocked. The lower opening of the funnel was then unlocked, and the time necessary for the entire sample to flow out of the funnel was measured [54]. For each material, three determinations were made, and the mean ± standard deviation is reported.

2.3. Tapped Density Test

Tapped Density Tester JV 100i (Copley Scientific, Nottingham, UK) was used, and the determinations were conducted at room temperature (20–24 °C) and ambient relative humidity (40–60%). The analysis was conducted by introducing 70 mL of the powder sample under examination into the dry cylinder without packing. The cylinder was fixed on the top of the instrument. The instrument performed 250 taps per minute, and the cycle was repeated three times. This analysis was conducted in triplicate. The results obtained were expressed as Compressibility Index C.I. (Equation (1)) and the closely related Hausner Ratio H.R. (Equation (2)), which are two commonly used indices to describe the flow characteristics of powders and are reported in the official European Pharmacopeia [54,55].

$$C.I.={\displaystyle \frac{\left(V_0-V_f\right)·100}{V_0}}$$

(1)

$$H.R.={\displaystyle \frac{V_0}{V_f}}$$

(2)

where V₀ is the apparent volume of powder before packing, and V_f is the final apparent volume of the powder sample after tapping. The values assumed by these indicators describe the flow behavior of powder, as indicated in

Table 2. Classification of powder flow behaviors based on the Compressibility Index (C.I.) and the Hausner Ratio (H.R.).

Flow Behavior	C.I. [%]	H.R.
Excellent	1–10	1.00–1.11
Good	11–15	1.12–1.18
Fair	16–20	1.19–1.25
Passable	21–25	1.26–1.34
Poor	26–31	1.35–1.45
Very poor	32–37	1.46–1.59
Very, very poor	>38	>1.60

.

2.4. Shear Cell Analyses

For the rheological analysis of the powders, the Brookfield PFT Powder Flow Tester (AMETEK Brookfield, Middleboro, MA, USA), equipped with an aluminum annular shear cell and a vane lid, was used. The custom flow function test provided by the Powder Flow Pro Software was employed to collect the data. The results were then collected and analyzed using dedicated software written in Python 3.9. According to the experimental procedure, the sample was subjected to pre-shear at a constant normal load (pre-consolidation stress) until the shear stress reached a steady-state condition. The sample was subsequently sheared under normal stress lower than the pre-consolidation stress until reaching a maximum shear stress, at which the material yielded (incipient flow condition). This procedure was repeated three times at decreasing normal stresses to determine the internal yield locus.

For each sample, yield loci were obtained at pre-consolidation stress values of 0.289, 0.584, 1.180, 2.385, and 4.819 kPa. Using Mohr circle analysis, two parameters were calculated: the unconfined yield stress (σ_c) and the major principal consolidation stress (σ₁). These values were used to construct the flow function (FF) of the material. The ratio (ff_c) of σ₁ to σ_c indicates powder flowability. According to Jenike’s classification [47,56], reported in

Table 3. Powder flow behavior based on Jenike classification [47].

Flow Behavior	ffc
Not flowing	<1
Very cohesive	1–2
Cohesive	2–4
Easy flowing	4–10
Free flowing	>10

, larger ff_c values correspond to better powder flow.

The wall friction test was performed using the shear cell and a different upper lid geometry made of stainless steel AISI 304 (2B finish). The standard wall function test provided by the shear cell software was used. Pairs of wall normal stress and wall shear stress values under steady-state conditions are plotted on a σ-τ diagram. The resulting curve, known as the wall yield locus, can be linearly fitted to determine the wall friction angle from its slope. This test measures the wall friction angle after 0 and 6 mm displacement of the lid on the powder. Evaluating the wall friction angle allowed us to assess whether the addition of the alternative excipients could impact powder–wall interactions, which are critical for processability in industrial equipment.

All the rheological experiments were performed at 23 °C ± 0.05 controlled with a Peltier system and relative humidity of 40–60%.

2.5. Preparation of Powder Mixtures

Three different commercial formulations of tablets, namely Product 1, Product 2, and Product 3, with active ingredients and conventional excipients, were selected for the study.

Product 1, containing 10% w/w of active ingredient (lipophilic vitamin), is intended for the formulation of chewable tablets with the function of supporting the immune system and maintaining normal osteoarticular function. It is made up of isomalt and mannitol acting as diluents at a total concentration of 87% w/w, 1.5% w/w magnesium stearate, lubricants, and an anti-caking agent.

Product 2 is a formulation for tablets made up of 40% w/w of active ingredients (hydrophilic vitamin), microcrystalline cellulose (MC) and calcium phosphate (CP) at a total concentration of 50% w/w which act as diluents; 5% w/w hydroxypropyl cellulose (HPC), which acts as a disintegrant; 2% w/w of glyceryl behenate (GB); and 0.75% w/w of magnesium stearate (MS) with a lubricating and anti-caking function.

Product 3, containing 25% active ingredient (botanical extract), is intended for the formulation of tablets with prebiotic function. It is composed of microcrystalline cellulose (MC) and calcium phosphate (CP), which act as diluents/bulking agents at a total concentration of 63% w/w, 3% w/w of carboxymethylcellulose (CMC), which acts as a stabilizer, 1.25% w/w of magnesium stearate (MS) and glyceryl behenate (GB) at 3% w/w with the function of lubricants, and 6% w/w of silicon dioxide (S1 and S2) as an anti-caking agent.

Powders were combined in a 250 mL beaker and gently mixed with a spatula until homogeneous. Powders were sieved through a 500 µm mesh to remove or break any agglomerates. Homogeneity was verified visually and by confirming the absence of agglomerates after sieving. The characteristics and performances of the three original formulations are summarized in Table S1.

The formulations with alternative excipients were prepared following the same procedure as conventional ones.

2.6. Compression of Powder Mixtures

The original powder mixtures with conventional excipients (Product 1, Product 2, and Product 3) and the reformulated ones with alternative excipients (Mixture 1E, 2D, 3L) were compressed to obtain tablets. 500 g of powder mixtures were sieved through a 500 µm sieve and homogenized using MP-6 L mixer (Multigel Srl, Firenze, Italy). Mixtures were then pressed through PZ-Zero rotary tableting machines (B&D Italia Srl, Monza e Brianza, Italy) equipped with an 8-punch turret in order to obtain regular tablets (Products 2 and 3) and chewable tablets (Product 1). The compression force of the machine was max 60 kN, the loading speed was 10–70 rpm, the punch dimension was 8 mm in circular (Product 1) and oval (Product 2 and 3) shapes. Tablets’ weight, hardness, thickness, friability, and abrasion and disaggregation tests were performed according to the European Pharmacopeia. Tablet hardness was measured by a manual durometer DM-500 with a loading cell (Elab, Monza Brianza, Italy). Tablet’s thickness was measured by a digital 0–150 mm caliper (Mitutoyo, Kawasaki, Japan). Tablets’ friability and abrasion were measured by the friability meter Tar II (Erweka, Langen, Germany), and the weight loss percentages compared to initial weight were calculated after 24 min for regular tablets and 4 min for chewable tablets. Hardness, thickness, friability, and abrasion tests were performed on ten tablets, and the average value was considered. Uniformity of weight test was performed on twenty tablets. Tablets disaggregation test (3 tablets in 800 mL of water) was performed using the Erweka ZT322 disintegration tester. All experiments were performed under controlled laboratory conditions, at room temperature (20–23 °C), and ambient relative humidity (40–60%).

3. Results

3.1. Characterization of Lubricant Excipients

In the first part of this work, the rheological properties of individual excipients, both conventional and alternative, were characterized and compared. Excipients were analyzed using a flowability tester, a tapped density tester, and a rheometer equipped with a powder shear cell. The first excipients to be analyzed were those with the function of lubricants. Glyceryl behenate (GB) was used to replace magnesium stearate (MS). On the flowability tester, neither excipient flowed through any diameter: the establishment of inter-particle interactions limited the powders’ flowability through the funnel orifice, regardless of its diameter. GB exhibited a lower Hausner Ratio and Compressibility Index calculated using the tapped density tester compared to magnesium stearate. Specifically, MS exhibited an H.R. of 1.38 and a C.I. of 27.42%, falling into the category of powders with poor flow behavior according to the official classification indicated in the European Pharmacopeia. GB, on the other hand, showed an H.R. of 1.25 and a C.I. of 19.67%, falling into the category of powders with fair flow behavior.

Figure 1 shows the flow functions of the lubricants obtained by rheological analysis with the shear cell. The MS trend at low consolidation stress was localized in the “very cohesive” area to end in the “cohesive” area at high consolidation stress; GB was placed in the “cohesive” range, thus highlighting better flowability at low consolidation stress compared to MS.

3.2. Characterization of Diluent Excipients

The results of the flowability test, tapped density test, and shear cell test of conventional and alternative excipients are summarized in

Table 4. Results obtained with the flowability tester (funnel with orifices of 25-, 15-, and 10 mm diameters) and the tapped density tester (Hausner Ratio H.R. and Compressibility Index C.I.) for the conventional and alternative diluents.

Powder	Flowability Test [sec]			Tapped Density Test
	25 mm	15 mm	10 mm	H.R.	C.I. [%]
Conventional excipients
MC	5.15 ± 0.19	Not flowing	Not flowing	1.36	26.47
CMC	Not flowing	Not flowing	Not flowing	1.40	28.33
CP	0.85 ± 0.10	2.82 ± 0.08	7.65 ± 0.04	1.11	10.01
HPC	Not flowing	Not flowing	Not flowing	1.22	18.09
S1	Not flowing	Not flowing	Not flowing	1.20	16.39
S2	2.32 ± 0.02	8.66 ± 0.03	25.32 ± 0.18	1.09	8.57
I	1.93 ± 0.05	6.49 ± 0.06	17.61 ± 0.25	1.23	19.57
M	Not flowing	Not flowing	Not flowing	1.25	20.00
Alternative excipients
FOS	1.14 ± 0.22	3.85 ± 0.04	10.63 ± 1.06	1.11	10.00
GOS	Not flowing	Not flowing	Not flowing	1.23	18.78
MD	Not flowing	Not flowing	Not flowing	1.30	22.95
LBG	Not flowing	Not flowing	Not flowing	1.22	18.33
AG	2.73 ± 0.06	9.59 ± 0.03	27.40 ± 0.34	1.23	18.57

.

On the flowability tester, it can be observed that among the conventional excipients, only CP, S2, and I showed good flowability at every diameter of the flowability tester, but only the first two exhibited “excellent” flow behavior according to their H.R. and C.I. values. MC flowed only through the 25 mm diameter orifice, and its tapped density results indicated ‘poor’ flow behavior.

The other conventional excipients did not flow through the flowability tester, showing H.R. and C.I. values that made them fall in the category of “fair” (HPC and S1) and “poor” (CMC) flow behavior. FOS exhibited ‘excellent’ flowability in both the flowability tester and the tapped density tester. Regarding the alternative excipients, only FOS presented “excellent” flowability values, as evidenced by the values assumed by the H.R. and C.I. and by its ability to flow rapidly through all funnel diameters.

The parameters calculated from the rheological tests of conventional and alternative diluent excipients by means of a powder shear cell are listed in

Table 5. Results of the shear cell test (flow function at normal stress of 0.6 kPa and 6 kPa and relative flow classification) for the conventional and alternative diluents.

Powder	Shear Cell Test
	ffc [0.6 kPa]	Classification	ffc [6 kPa]	Classification
Conventional excipients
MC	7.01	Easy flowing	18.81	Free flowing
CMC	3.37	Cohesive	5.74	Easy flowing
CP	10.72	Free flowing	107.22	Free flowing
HPC	0.96	Not flowing	1.47	Very cohesive
S1	1.74	Very cohesive	2.46	Cohesive
S2	24.34	Free flowing	20.79	Free flowing
I	9.45	Easy flowing	24.11	Free flowing
M	2.90	Cohesive	6.17	Easy flowing
Alternative excipients
FOS	14.66	Free flowing	11.97	Free flowing
GOS	2.93	Cohesive	4.56	Easy flowing
MD	2.81	Cohesive	4.93	Easy flowing
LBG	2.59	Cohesive	9.24	Easy flowing
AG	8.11	Easy flowing	10.09	Free flowing

. We considered two values of consolidation stress (0.6 kPa and 6 kPa) to evaluate the consistency of powder flow behavior throughout the stresses to which it is subjected. The flow function values obtained showed that the conventional excipients exhibiting free-flowing behavior were CP, MC, and S2. CMC had an easy-flowing rheological behavior at higher consolidation stress, whereas the other conventional excipients, S1 and HPC, were located between the ‘cohesive’ and ‘very cohesive’ areas. Among the alternative excipients, only FOS exhibited a free-flowing rheological pattern in the entire consolidation state range explored (Figure 2); LBG, GOS, and MD were more cohesive powders. These differences are primarily attributed to particle size: finer powders, like HPC, S1, and MD, often lead to decreased flowability due to stronger interparticle attraction. It is well established that powder flowability is stress-dependent, as the ratio between applied consolidation stress and cohesive interparticle forces determines flow behavior. Generally, flowability tends to decrease as the major consolidation stress (σ₁) decreases: at lower applied stresses, with cohesive forces remaining constant, the relative influence of interparticle attraction increases, resulting in reduced flowability. This trend was observed for powders with finer particle sizes, such as CMC, M, and LBG, which exhibited lower ff_c values at 0.6 kPa compared to 6 kPa, indicating reduced flowability at lower consolidation stresses. Conversely, granular and low-cohesion excipients, such as FOS, CP, and silica S2, showed minimal stress sensitivity and maintained a consistently free-flowing profile across the entire consolidation range.

At the end of this first phase of characterization of the excipients, FOS and arabinogalactans were selected as alternative diluents to replace the conventional ones in the reformulation of existing tablet formulations, since they showed good flow properties and a free-flowing rheological pattern. The physical and mechanical properties of FOS were comparable to those shown by the conventional excipients calcium phosphate, isomalt, and silicon dioxide S1.

3.3. Reformulation of Product 1

Systematic analyses were conducted to investigate the partial or total replacement of conventional excipients (lubricants and diluents) with the selected alternative excipients (FOS, AG, GB). This must be achieved without compromising the technical and mechanical properties of the original formula. In the first step, the mechanical properties of the original formulation were compared with Mixture 1A, in which the conventional lubricant magnesium stearate was substituted with glyceryl behenate at the same concentration (1.5% w/w). The results obtained with the flowability tester (

Table 6. Results obtained with the flowability tester (funnel with orifices of 25-, 15-, and 10 mm diameters) and the tapped density tester (Hausner Ratio H.R. and Compressibility Index C.I.) for Product 1 original mixture and Mixture 1A.

Powder	Flowability Test [sec]			Tapped Density Test
	25 mm	15 mm	10 mm	H.R.	C.I. [%]
Product 1	2.14 ± 0.25	5.60 ± 0.65	16.29 ± 0.02	1.16	14.00
Mixture 1A	1.91 ± 0.06	7.21 ± 0.01	19.72 ± 0.59	1.16	13.81

) did not highlight any significant differences between the original mixture and Mixture 1A. Both exhibited similar values of the Hausner Ratio and the Compressibility Index, classifying them as having “fair” flowability according to the European Pharmacopeia guidelines.

Rheological analyses on the shear cell further corroborated these findings. Mixture 1A displayed a slightly lower flow function compared with the original mixture, yet both remained within the “free flowing” range (Figure 3).

Subsequently, formulations were developed in which, in addition to the lubricant replacement, a complete or partial substitution of the primary diluents, isomalt and mannitol (I + M total concentration 87% w/w), was implemented. This substitution involved the prebiotic excipients FOS and arabinogalactans (AG), which, in the preliminary characterization phase of this work, exhibited a free-flowing rheological behavior. Although all mixtures flowed through the three diameters of the flowability tester, the H.R. and the C.I. of Mixture 1B (involving total diluent replacement with FOS), Mixture 1C (involving partial diluents replacement with FOS), and Mixture 1D (involving partial diluents replacement with FOS and arabinogalactans) indicated “good” flowability, compared to the “fair” flow behavior of the original mixture (

Table 7. Results obtained with the tapped density tester (Hausner Ratio H.R. and Compressibility Index C.I.) for Mixture 1A, Mixture 1B, Mixture 1C, and Mixture 1D.

Powder	I + M [% w/w]	FOS [% w/w]	AG [% w/w]	Flowability Test [sec]			Tapped Density Test
				25 mm	15 mm	10 mm	H.R.	C.I. [%]
Mixture 1A	87	-	-	1.91 ± 0.06	7.21 ± 0.01	19.72 ± 0.59	1.16	13.81
Mixture 1B	-	87	-	2.04 ± 0.08	7.06 ± 0.24	17.81 ± 0.44	1.11	10.14
Mixture 1C	43.5	43.5	-	1.35 ± 0.02	4.47 ± 0.04	12.44 ± 0.17	1.13	11.43
Mixture 1D	41	43.5	2.5	1.75 ± 0.09	5.42 ± 0.08	14.55 ± 0.27	1.14	12.38

).

The shear cell measurements showed that Mixture 1D had a free-flowing behavior even at low consolidation stresses compared to other mixtures (Figure 4), indicating how partial replacement of conventional diluent excipients is preferable to total replacement. Moreover, Mixture 1B, in which the conventional diluents were totally replaced by FOS, resulted in capping during tablet compression. On the other hand, the partial substitution of conventional diluents allowed for obtaining of stable and homogeneous tablets.

Increasing the concentration of Glyceryl behenate (GB) could be necessary to prevent friction and sticking phenomena between the powder and the material from which the tablet press is made. No significant differences were found in the flowability properties of powder mixtures in which the concentration of lubricant was increased from 1.5% w/w (Mixture 1D) to 3% w/w (Mixture 1E) and 5% w/w (Mixture 1F) (

Table 8. Results obtained with the flowability tester (funnel with orifices of 25-, 15-, and 10 mm diameters) and the tapped density tester (Hausner Ratio H.R. and Compressibility Index C.I.) and shear cell test (flow function at normal stress of 0.5 kPa and relative flow classification, wall friction angle at 4.8 kPa) for Product 1 original mixture, Mixture 1D, Mixture 1E, and Mixture 1F.

Powder	M + I [% w/w]	FOS [% w/w]	AG [% w/w]	GB [% w/w]	Tapped Density Test		Shear Cell Test
					H.R.	C.I. [%]	ffc	Classification	Friction Angle [°]
Original	87	-	-	-	1.16	14.00	9.98	Easy flowing	13.61
Mixture 1D	41	43.5	2.5	1.5	1.14	12.38	13.97	Free flowing	12.44
Mixture 1E	38.5	43.5	2.5	3	1.13	11.97	16.28	Free flowing	12.65
Mixture 1F	37.5	43.5	2.5	5	1.13	11.43	12.17	Free flowing	12.33

). Wall friction analyses were also conducted to assess the possible presence of friction between the mixture and the walls of the handling device to avoid issues during the various stages of industrial production. The results showed that the partial replacement of conventional excipients with alternative ones lowers the friction between the powder and the stainless-steel walls and improves the flow properties. Considering the overall results, Mixture 1E was selected as the most promising for further compression tests and tablet manufacturing.

3.4. Reformulation of Product 2

As a first step, MS was all replaced with GB, formulating Mixture 2A that contained GB at a total concentration of 2.75%. In

Table 9. Results obtained with the flowability tester (funnel with orifices of 25-, 15-, and 10 mm diameters) and the tapped density tester (Hausner Ratio H.R. and Compressibility Index C.I.) for Product 2 original mixture and Mixture 2A.

Powder	Flowability Test [sec]			Tapped Density Test
	25 mm	15 mm	10 mm	H.R.	C.I. [%]
Original	3.70 ± 0.59	8.44 ± 0.82	Not flowing	1.21	17.31
Mixture 2A	3.75 ± 0.61	Not flowing	Not flowing	1.26	20.77

, Mixture 2A showed a lower ability to flow compared to the original mixture, probably due to a very high percentage of GB. Furthermore, in Mixture 2A, the Hausner ratio and the Compressibility index are higher than the original ones, going from a “fair” to “acceptable” sliding attitude.

Subsequently, possible synergistic actions between the alternative diluent excipients and GB were evaluated, formulating mixtures that contained a partial replacement of CP and MC with FOS. In

Table 10. Results obtained with the tapped density tester (Hausner Ratio H.R. and Compressibility Index C.I.) for Product 2 original mixture, Mixture 2B, and Mixture 2C.

Powder	MC [% w/w]	CP [% w/w]	FOS [% w/w]	Flowability Test [sec]			Tapped Density Test
				25 mm	15 mm	10 mm	H.R.	C.I. [%]
Mixture 2A	29	20	-	3.75 ± 0.61	Not flowing	Not flowing	1.26	20.77
Mixture 2B	14	10	24	2.86 ± 0.40	8.13 ± 0.56	Not flowing	1.24	19.52
Mixture 2C	19	-	30	2.73 ± 0.52	7.77 ± 0.28	22.54 ± 0.54	1.17	14.29

, it can be observed that from the results obtained with the flowability tester and the tapped density tester, Mixture 2B, containing a lower concentration of MC and half the concentration of CP than the original formula, led to a mixture that did not flow through the smallest opening of the funnel. Mixture 2C, in which the percentage of FOS was increased and CP was totally removed, flowed through all the openings of the flowability tester. The tapped density-derived indexes measured for Mixture 2C were lower compared to the other mixtures, with a “good” flow behavior.

Mixture 2D containing the association between the alternative lubricant GB (2.75% w/w), the alternative diluent excipients FOS (27.5% w/w), and Arabinogalactan (AG 2.5% w/w) was prepared and analyzed, showing good flow behavior. These results were confirmed by the shear cell rheological analysis (Figure 5). The partial replacement of common excipients with FOS significantly improved the flow properties of the mixtures. In particular, the original mixture exhibited a flow function located within the “easy flowing” range, while Mixture 2D presented a curve within the “free flowing” area.

The results showed that the replacement of conventional excipients lowered the friction between the powder and the stainless-steel walls, since the angle of friction measured at a normal stress of 4.8 kPa was 13.16° for the original mixture and 10.31° for Mixture 2D. Considering the overall results, mixture 2D was selected as the most promising for further compression tests and tablet manufacturing.

3.5. Reformulation of Product 3

As a first step, MS was replaced with GB used at two different concentrations, 4.25% w/w and 3% w/w. The data obtained from the flowability tester showed no differences between the three mixtures compared, since they all flowed only at 25 mm and 15 mm diameters, maintaining a very similar flow time (

Table 11. Results obtained with the tapped density tester (Hausner Ratio H.R. and Compressibility Index C.I.) for Product 3 original mixture, Mixture 3A, and Mixture 3B.

Powder	MS [% w/w]	GB [% w/w]	Flowability Test [sec]			Tapped Density Test
			25 mm	15 mm	10 mm	H.R.	C.I. [%]
Original	3	1.25	5.08 ± 1.01	12.20 ± 2.14	Not flowing	1.29	22.17
Mixture 3A	-	4.25	4.07 ± 0.35	12.50 ± 1.67	Not flowing	1.27	20.95
Mixture 3B	-	3	3.73 ± 0.69	11.94 ± 1.80	Not flowing	1.23	18.57

). A significant difference can be noted in the Hausner and Compressibility indices, which assumed lower values in mixture 3B, showing a “fair” flow behavior. This means that high percentages of GB did not improve the mixture flow properties. For this reason, all the subsequent formulations were carried out keeping the percentage of this ingredient constant at 3% w/w.

The conventional diluents, excipients MC and CP, were replaced with FOS. From the results obtained with the flowability tester, it can be observed how the total or partial replacement of the conventional excipients was useful in significantly improving the flow properties; in fact, Mixture 3C and Mixture 3D flowed at all the orifices of the instrument, while Mixture 3B and the original one did not flow at a diameter of 10 mm (

Table 12. Results obtained with the tapped density tester (Hausner Ratio H.R. and Compressibility Index C.I.) for Mixture 3B, Mixture 3C, and Mixture 3D.

Powder	MC [% w/w]	CP [% w/w]	FOS [% w/w]	Flowability Test [sec]			Tapped Density Test
				25 mm	15 mm	10 mm	H.R.	C.I. [%]
Mixture 3B	36	26	-	3.73 ± 0.69	11.94 ± 1.80	Not flowing	1.23	18.57
Mixture 3C	-	-	64	2.64 ± 0.37	12.45 ± 1.07	25.42 ± 5.39	1.16	13.81
Mixture 3D	36	-	26	3.85 ± 0.66	13.37 ± 0.49	36.44 ± 3.64	1.20	16.66

). The Hausner Ratio and the Compressibility Index were lower than the mixture with conventional diluents, as the new powders conferred a “good” attitude to flow.

The Mixture 3C, due to the presence of high concentrations of FOS, which are characterized by very low cohesiveness and low compressibility, caused the capping phenomenon after the preliminary tableting processes, consisting of the partial separation of the top part of the tablet from the tablet body. Mixture 3D resulted in the formation of hard tablets showing a visible lack of homogeneity with the presence of white lines and spots, due to the high concentration of silicon dioxide. This formula is characterized by the presence of two different types of silicon dioxide: 1% w/w S1 and 5% w/w S2. Both ingredients function as anti-caking agents; however, S2 additionally exhibits a granular morphology that enhances flowability and humidity absorption. With the aim of improving the appearance of the mixture and making the surface of the resulting tablets more homogeneous, a systematic formulation was carried out, which included different concentrations and different ratios between the two silicon dioxides. For this systematic approach, a mixture containing 20% w/w of MC partially replaced with FOS was selected. Flowability tester graphs show that S1:S2 ratios of 1:1 and 1:2.5 improved the mixtures’ flow properties, as Mixture 3H and Mixture 3I flowed to all the diameters of the funnel orifice (

Table 13. Results obtained with the flowability tester (funnel with orifices of 25-, 15-, and 10 mm diameters) and the tapped density tester (Hausner Ratio H.R. and Compressibility Index C.I.) for Product 3 original mixture, Mixtures 3E, 3F, 3G, 3H, and 3I.

Powder	MC [% w/w]	FOS [% w/w]	S1 [% w/w]	S2 [% w/w]	Flowability Test [sec]			Tapped Density Test
					25 mm	15 mm	10 mm	H.R.	C.I. [%]
Original	87	-	1	5	5.08 ± 1.01	12.20 ± 2.14	Not flowing	1.29	22.17
Mixture 3E	20	50	-	-	4.07 ± 1.39	Not flowing	Not flowing	1.32	24.07
Mixture 3F	20	47.5	-	2.5	2.45 ± 0.61	Not flowing	Not flowing	1.30	22.86
Mixture 3G	20	47.5	2.5	-	6.25 ± 0.22	20.35 ± 0.48	Not flowing	1.27	21.43
Mixture 3H	20	46	2	2	4.64 ± 0.34	13.89 ± 1.44	28.72 ± 8.55	1.22	18.10
Mixture 3I	20	46.5	1	2.5	3.74 ± 0.31	12.71 ± 2.51	33.80 ± 2.60	1.18	15.60

). Both the silica-free Mixture 3E and Mixture 3F with only S2 flowed only through the 25 mm orifice, while Mixture 3G with only S1 flowed through the 25 mm and 15 mm orifices, but not through the 10 mm orifice. From these results, it can be concluded that the total replacement of S1 and S2 with FOS did not improve the physical flow properties of the system. In fact, the Mixture 3E also showed a higher H.R. and C.I. On the contrary, Mixtures 3H and 3I, with, respectively, 1:1 and 1:2.5 ratios between S1 and S2, showed a “good” and “fair” flow behavior, according to the tapped density test results.

The data obtained from the rheological analysis with the shear cell confirmed that the total replacement of silicon dioxide led to lower ff_c values than the other mixtures included in the “easy flowing” range. For Mixtures 3H and 3I, the flow functions were in the “free flowing” zone (Figure 6).

Finally, a further comparison was carried out between the original mixture and Mixture 3L by introducing, in addition to the alternative lubricant glyceryl behenate (3% w/w) and diluent FOS (46% w/w), also arabinogalactan (2.5% w/w). A 1:1 ratio of S1 to S2 was used, since it was the one that did not alter the density and flow properties conferred by the excipients introduced into the mixture. The rheological analysis did not report significant differences between the original and Mixture 3L, since they both showed an “easy-flowing” behavior at low consolidation stress and a “free-flowing” behavior at high consolidation stress (Figure 7). Therefore, the replacement of the conventional excipients with innovative ones led to the formulation of a mixture that fell within the same flow area, with better flow properties as measured by the flowability tester and the tapped density tester, and with the addition of health properties to the final product. The wall friction angle measured at a normal stress of 4.8 kPa for the original mixture was 17.41°; whereas for Mixture 3L was 13.98°. Considering the overall results, Mixture 3L was selected as the most promising for further compression tests and tablet manufacturing.

3.6. Tablets Production with Alternative Excipients

The results of the compression tests of the selected alternative mixtures and the comparison with the original tablets are presented. The compression of selected alternative powder mixtures 1F, 2D, and 3L allowed the production of tablets in accordance with the physical parameters of the original products 1, 2, and 3. In

Table 14. Compression parameters and disaggregation times of tablets obtained from commercial (1, 2, 3) and alternative (1F, 2D, 3L) mixtures.

Tablet	Weight [mg]	Compression Force [KgN]	Hardness [N]	Thickness [mm]	Friability and Abrasion [%]	Disaggregation Time [min]
1	204.7 ± 1.5	10	11.4 ± 2.0	3.56 ± 0.02	<1	Not measured
1F	203.1 ± 1.3	10	11.5 ± 0.8	3.55 ± 0.01	<1	Not measured
2	1209.1 ± 5.4	34	17.5 ± 0.3	6.49 ± 0.01	<1	20 ± 0.2
2D	1193 ± 8.8	35	24.1 ± 0.9	6.93 ± 0.03	<1	23 ± 1.4
3	1096.6 ± 18.8	27	25.2 ± 2.4	6.62 ± 0.02	<1	32 ± 1.8
3L	1101.1 ± 13.8	33	49.0 ± 1.9	6.47 ± 0.06	<1	40 ± 2.5

are reported the values of hardness, thickness, friability, abrasion, and disaggregation times related to tablets obtained from conventional powder mixtures (products 1,2,3) compared to tablets obtained from the most promising alternative powder mixtures (1F, 2D, and 3L). The disaggregation times related to formulations 1 and 1F were not measured, as they were chewable tablets.

Results indicate that the inclusion of alternative excipients does not affect tablet weight, thickness, friability, and abrasion, while hardness and disaggregation times increase in regular tablets obtained from alternative mixtures (2D and 3L) compared to conventional ones (2 and 3). FOS is the most abundant ingredient in all alternative mixtures, indicating the great impact of this raw material on compression results. In formulations 1 and 1F (chewable tablets), the presence of alternative excipients does not change the hardness in a significant way, suggesting that compression force and overall formulation composition also play a role in tablet manufacturing.

4. Discussion

The systematic methodological approach adopted in this study is useful for characterizing and comparing conventional and alternative excipients and powder mixtures. The combined use of the flowability tester, tapped density tester, and shear cell analysis provided complementary insights into powder behavior across different consolidation states and handling conditions. This multi-instrumental strategy enabled the identification of critical differences in flow and cohesion, allowing a comprehensive mapping of excipient performance. This approach supports rational tablet formulation design by guiding the selection or substitution of excipients based not only on their technological role but also on their mechanical and functional behavior. Shear cell analysis allowed the evaluation of powder behavior both at low consolidation states, related to pouring and filling phases, and at high consolidation states, related to compression phases. However, the analyses have shown that the use of the shear cell is more suitable for testing the flow properties of single excipients and cohesive powders, while powders that fall into the category of free- or easy-flowing are often not well characterized and differentiated from each other correctly. Furthermore, the presence of different powders with different particle sizes in the mixtures can impact the sensitivity and reproducibility of the obtained flow curves.

The rheological characterization of conventional and alternative excipients highlighted significant differences in flowability and compressibility, which are critical parameters for their industrial application in solid oral dosage forms. Regarding lubricants, the replacement of conventional magnesium stearate (MS), conventionally used as an anti-caking agent and lubricant in the formulation of oral solid dosage pharmaceutics and food supplements, with glyceryl behenate (GB), a mixture of mono-, di- and triglycerides of behenic acid, employed within a concentration range of 1–3%, resulted in lower cohesiveness and improved flow properties at low consolidation stresses. These findings are consistent with previous reports showing that GB can act as an efficient lubricant in direct compression, sometimes reducing the reliance on MS in binary mixtures or nanoparticle-based systems [57,58]. In agreement with prior studies, our results confirm that, even if it cannot be considered a full equivalent of MS in terms of lubrication efficiency, GB may represent a viable alternative in selected formulas, not only maintaining technological properties but also contributing to formulation consistency and controlled release [23].

Among the powders used as diluent excipients, bulking agents, and stabilizers for the formulation of pharmaceutical and nutraceutical tablets, there are

-

inorganic compounds: silicon dioxide (S1 and S2) and calcium phosphate (CP);

-

organic compounds: isomalt (I), mannitol (M), microcrystalline cellulose (MC), hydroxypropyl cellulose (HPC), and carboxymethyl cellulose (CMC).

We compared the flowability performances of these conventional excipients with those of alternative ones with health-functional properties:

-

FOS and GOS, which, in addition to acting as a diluent/binder, also perform a prebiotic function;

-

Carob gum (LBG), which promotes metabolic control and performs muco-adhesion function within the intestinal walls [59], modulating the release of the active ingredient;

-

Maltodextrins (MD) from tapioca starch, which have a lower glycemic index than the maltodextrins normally used;

-

Arabinogalactans (AG) from larch with prebiotic action, which have immunomodulatory action and are useful in metabolic control.

Among the alternative candidates, FOS displayed excellent flowability across all testing methods. This is in line with established evidence that particle size and surface morphology strongly influence powder flow, with finer particles generally exhibiting greater cohesiveness and poorer flowability [60]. In our study, conventional excipients such as HPC, silica S1, and MD confirmed this trend, while FOS exhibited superior free-flowing behavior. This result is particularly relevant, as it demonstrates that even low percentages of FOS can achieve technological performance comparable to conventional excipients while also providing prebiotic benefits.

Formulation trials indicated that complete replacement of conventional diluents with FOS (Mixture 3C) often resulted in capping and reduced mechanical integrity, highlighting the limitations of excessive cohesiveness reduction. Conversely, partial substitutions (Mixtures 1F, 2D, and 3L) produced powders with “free-flowing” behavior and yielded stable, homogeneous tablets. Larch arabinogalactans (AG) at 2.5% proved particularly effective as a complementary excipient in association with FOS, combining satisfactory technological performance with immunomodulatory health benefits. Wall friction analyses showed reduced friction angles in mixtures containing alternative excipients, indicating a lower tendency of powders to adhere to stainless-steel surfaces. This reduction improves handling during industrial processing, while overall flowability remains primarily influenced by interparticle cohesion as assessed through shear cell and density-based measurements. [61]. These results suggest that a balanced combination of conventional and alternative excipients is the most promising strategy. Such findings expand upon earlier studies that primarily investigated excipients in isolation or simple binary systems [59] by demonstrating the practical implications of substitution strategies in complex, multi-component formulations.

Final compression tests confirmed that the incorporation of alternative excipients does not affect critical quality parameters such as tablet weight, thickness, friability, and abrasion. However, tablets obtained from alternative mixtures exhibited increased hardness and prolonged disintegration times compared with their conventional counterparts. A good correlation between hardness and disaggregation times was also obtained in previous studies [62,63,64], suggesting a higher binding activity of alternative mixtures compared to conventional ones, with FOS emerging as the most influential component. FOS exhibits a greater tendency to undergo plastic deformation during compression, which promotes stronger interparticle bonding and, consequently, the formation of harder tablets. In addition, arabinogalactan could contribute to increased matrix cohesiveness, further enhancing tablet strength. These combined effects also explain the longer disintegration times recorded for the corresponding formulations. Although the literature demonstrates that sugars and polyols (e.g., maltodextrins, mannitol, isomalt) can act as filler-binders and significantly affect tablet hardness and disintegration [65,66], direct peer-reviewed evidence specifically attributing enhanced binding activity to FOS is limited and does not provide comprehensive rheomechanical data. Therefore, our experimental demonstration that FOS markedly affects the compression performance constitutes a novel contribution to the field and fills an existing gap in published evidence.

Taken together, these findings confirm previously established relationships between cohesion, flowability, and compressibility, while extending current knowledge by systematically demonstrating the impact of alternative excipients with health-promoting properties (e.g., prebiotic, immunomodulatory) on technological performance in full tablet formulations. The novelty of this work lies in (i) the simultaneous evaluation of excipient functionality and processability, (ii) the demonstration that partial replacement rather than complete substitution yields optimal performance, and (iii) the integration of multiple rheological and mechanical characterization methods to capture powder behavior under industrially relevant stress conditions. Beyond its technological findings, this systematic workflow provides a practical decision-making tool for anticipating processing issues before scale-up, thereby reducing development time, limiting material waste, and supporting a more efficient transition to industrial production.

Tablet performance is influenced by several interconnected variables, including particle size distribution, residual moisture, material deformability, and excipient compatibility. These factors may affect powder packing, die filling, and the ability of particles to form stable interparticle bonds during compression. However, the primary determinants of manufacturability remain flowability, compressibility, and cohesion.

Although the experiments were performed at laboratory scale, the parameters evaluated in this study, i.e., flow function, tapped density-derived indices, and compressibility measurements, are all well-established predictors of large-scale manufacturability. These measurements correlate with hopper discharge behavior, bulk handling performance, feeder consistency, and die filling performance in industrial equipment, as demonstrated in classical powder-flow studies and shear-cell-based engineering approaches [67,68,69]. Implementation in commercial manufacturing would require pilot-scale trials, hopper discharge and feeder tests, and verification of compression performance under production conditions. Moreover, although rheological and mechanical measurements are strong predictors of manufacturability, they do not capture all sources of variability, such as environmental fluctuations or batch-to-batch differences in natural excipients. Future work could include pilot-scale validation and the evaluation of multiple batches to confirm the robustness of the observed trends.

5. Conclusions

The results of this project confirmed that the flowability tester, tapped density tester, and shear cell are useful in characterizing the flow properties of each excipient and mixture, allowing the prediction of their mechanical behavior and the prevention of issues during various stages of industrial production of dietary supplements in solid form. The combined use of these instrumental techniques highlighted the differences between the various powder excipients, enabling the evaluation of partially or totally replacing commonly used ones in product formulation with new ingredients that are distinguished by specific characteristics such as technology, health properties, functionality, and innovation. Combinations demonstrating equivalent functionality to commonly used excipients, such as fillers, diluents, and lubricants, but exhibiting superior flow properties, along with additional health benefits and innovative attributes, were incorporated into formulations for the development of solid nutraceutical products. The inclusion of associations of FOS, glyceryl behenate, and arabinogalactans led to a significant enhancement in the flow properties of the analyzed mixtures and enabled the achievement of compliant and acceptable alternative tablets compared to the original ones.

This instrumental protocol provides an efficient approach to supplement formulation, enabling rapid evaluation of excipients and accelerating product development. By predicting potential challenges during scale-up phases and ensuring product quality, this method supports a quality-by-design approach, resulting in products that meet the evolving needs of consumers.