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 CHEMICAL ENGINEERING TRANSACTIONS  
 

VOL. 44, 2015 

A publication of 

The Italian Association 
of Chemical Engineering 
Online at www.aidic.it/cet 

Guest Editors: Riccardo Guidetti, Luigi Bodria, Stanley Best
Copyright © 2015, AIDIC Servizi S.r.l., 
ISBN 978-88-95608-35-8; ISSN 2283-9216                                                                               
 

Hydrogel-Based Granular Phytostrengtheners  
for Prolonged Release: Production and Characterization 

Diego Caccavoa, Sara Casconea, Maria C. Amorosoa, Pietro Apicellaa, Gaetano 
Lambertia, Anna Angela Barbab 
a Department of Industrial Engineering, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy  
b Department of Pharmacy, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy 
dcaccavo@unisa.it 

Soil wellness is an indispensable requirement to obtain fruits and vegetables with finest quality and with high 
yields. To the purpose, periodical administrations of nutrients, as well as phytostrengtheners could be 
required. Crucial goals to maximize the economic and environmental sustainability of the whole cultivation are 
the decrease of the dosages number together with the increase of the active substance availability within the 
soil. With these aims a controlled release phytostrengtheners encapsulated in a granular Hydroxypropyl 
methylcellulose matrix has been developed exploiting the wet granulation process. The granular product has 
been analyzed in terms of Particle Size Distribution (PSD), morphology and flowability. The results showed the 
effectiveness of the granulation process and the good flowability of the granules, highly desirable features for 
the product handling and commercialization. 

1. Introduction 
The continuous population growth, along with the increased food quantity and quality requirements, binds the 
agricultural sector to use ever-larger quantities of fertilizer, phytostrengtheners and agrochemicals. However 
the massive use of these products presents economic and environmental drawbacks. The mainly 
environmental impacts can be linked to leaching phenomena that can cause ground water contamination or 
aquatic eutrophication as well as to soil pollution (Falciglia and Vagliasindi, 2013) and emission of greenhouse 
gases (e.g. nitrous oxides) (Chien et al., 2009). Hence, it is of vital importance to conceive and develop 
systems that can boost production and mitigate environmental impacts.  
To the purpose, Controlled Release Systems (CRSs) can represent a valid tool to achieve these goals, 
releasing ideally nutrients/agrochemicals along with the plant needs, for an entire cultivation cycle (Blouin and 
Rindt, 1967, Shaviv, 2001, Sempeho et al., 2014). Looking at Controlled Release Fertilizers (CRFs), they can 
be classified according to several authors (Trenkel, 1997, Shaviv, 2005, LinShu et al., 2008) in three major 
categories: i) Organic compounds: that can be sub-classified in natural or synthetic and/or in chemical 
decomposing or biological decomposing compounds; ii) Water soluble fertilizers with physical barriers: it can 
be sub-divided in coated granules and fertilizer matrices; iii) Inorganic low solubility compounds. 
The CRSs through coating technique have been the most studied, since the early 1960’s when the Tennessee 
Valley Authority proposed the process for the production of sulfur coated urea granules (Blouin and Rindt, 
1967). However, this system are subjected to the burst of the coating due to osmotic pressure and the 
complete release of the core content (Shaviv, 2005, LinShu et al., 2008). In attempt to overcome the 
“catastrophic release”, synthetic polymers (e.g. polyolefin, polyacrylic acid and mostly polyurethane) have 
been used to coat granules. 
On the other end the CRSs based on matrix encapsulation have been less investigated with respect to coated 
formulations (Shaviv, 2001), but particular emphasis, in the last years, has been pointed toward hydrophilic 
matrices able to form hydrogels (Rudzinski et al., 2002). Hydrogels are capable of imbibing large amounts of 
water or biological fluids (Peppas et al., 2000). When an Active Ingredient (AI) is encapsulated in this kind of 
system its release mechanism become quite complex and several steps can be identified. Briefly, when a dry 

                               
 
 

 

 
   

                                                  
DOI: 10.3303/CET1544040

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Please cite this article as: Caccavo D., Cascone S., Amoroso M., Apicella P., Lamberti G., Barba A.A., 2015, Hydrogel-based granular 
phytostrengtheners for prolonged release: production and characterization, Chemical Engineering Transactions, 44, 235-240   
DOI: 10.3303/CET1544040

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hydrogel matrix enters in contact with water, the solvent starts to penetrate inside the system, polymeric 
chains unfold so that a glass-rubbery transition occurs and a gel-like layer is formed. In the swollen region the 
contained AI molecules can easily diffuse toward the outer dissolution medium, once that they are dissolved. 
These properties have brought hydrogels to be one of the most abundant CRSs in the pharmaceutical field 
and their extension to the agricultural applications is particular attractive due to their additional property of 
water retention, that reduce water consumption and irrigation frequency, especially in drought areas (Azeem 
et al., 2014). Several attempts to produce hydrogel-based CRS for agricultural sector have been made, for 
both pesticides and fertilizers, using alginate (Roy et al., 2009), ethyl cellulose (Cea et al., 2010), chitosan 
(Corradini et al., 2010, Jamnongkan and Kaewpirom, 2010) and others natural and semi-natural polymers 
mostly in the forms of nano and micro-particles (Sempeho et al., 2014, Roy et al., 2014, Rudzinski et al., 
2002). However when it comes to hydrogel-based system, hydroxypropyl methylcellulose (HPMC) is one of 
the first choices for matrix formulation due to its nonionic nature, which makes its swelling behavior 
independent from the environmental pH, and cost effectiveness. It has been extensively used in 
pharmaceutical applications (Cascone et al., 2014) and very recently it has been employed with promising 
results in CRFs (Ureña-Amate et al., 2011, Melaj and Daraio, 2014).  

1.1 Aim of the work 

The aim of this work is to investigate the feasibility of Hydroxypropyl methylcellulose (HPMC) as controlled 
release granules for agricultural applications. Further aim is the characterization of the produced granules in 
terms of morphology, flowability, and granulometric properties. 

2. Materials and methods 
2.1 Materials 

Powders of HydroxyPropyl MethylCellulose (HPMC, Methocel K4M) were kindly supplied by Colorcon, 
Varese, Italy. Tequil® Multi, the reference phytostrengthener, was provided by Fertenia Srl, Bellizzi, Italy. 

2.2 Granulation process 

The wet granulation process was performed with a Caleva Multi Lab (from Caleva Process Solutions). Each 
granulation batch was carried out with 5 g of HPMC powder and 4 mL of wetting phase. Two different granular 
products were produced, varying the wetting phase composition: for the first one, “GC”, 4 mL of pure 
Tequil® Multi were used, for the second one, “GD”, 4 mL of Tequil® Multi diluted 1:5 with distilled water were 
used. The operative conditions were: blades rotation of 60 rpm and granulation time of 300 s with the addition 
of the wetting phase drop by drop with a syringe during the first 120 s. The product obtained from the 
granulator was forced to pass through a sieve with a mesh opening of 2 mm to emulate a milling process and 
therefore limiting the particle size distributions (PSDs). The granules were dried out in oven at 80°C overnight. 

2.3 Particle Size Distribution (PSD) from image analysis 

The PSD of the granular products were obtained through image analysis. Several samples pictures were 
taken and analyzed with the software Image-Pro Plus 6.0 (from Media Cybernetics) obtaining the mean 
diameter of each granule. The advantages of the PSD determination through image analysis, apart from 
gathering information on the particles shape, lie mainly in the possibility to choose the size intervals in which 

the particles have to be counted (e.g. not being constrained to a certain number of sieves). In this work a √2 
progression of the intervals dimension limits was applied obtaining 18 interval classes (Allen, 2003): from 0 to 
3,620.39 μm. The cumulative undersize numeric discrete distribution can be easily obtained considering its 
definition: 

Q , = nn  (1) 
Where with the subscript “0” the numeric distribution is indicated (related to the power of zero of the particles 
dimension), j characterizes the jth class, ni denotes the number of particles in the ith class and ntot the total 
number of particles. Equation (1) furthermore highlight the meaning of “undersize” since its value expresses 
the numeric fraction of particles below the upper limit size of the jth class. Furthermore it can be preferred to 
express the PSD in terms of cumulative undersize mass discrete distribution, weighing the importance of the 
particles dimensions not to their number but to their mass, that can be more significant in the processes of 
powder handling. 

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Q , = mm  (2) 
Where with the subscript “3” the mass distribution is indicated (related to the power of three of the particles 
dimension). In this case mi represents the mass of particles in the ith class and mtot the total mass of particles. 
The image analysis allows to obtain directly, from the raw data, only the numeric distribution since the analysis 
is based on the quantification of the number of particles and not of their mass/volume. However with some 
considerations it is possible to derive the mass distribution as well (Caccavo, 2011). 

2.4 Flowability 

The product flowability was analyzed through the determination of the Carr’s Index (CI) and Hausner Ratio 
(HR) (McGlinchey, 2008) and the angle of repose.  The CI and HR are functions of the bulk density (ρ ) and 
tapped density (ρ ). The bulk density of a powder is the ratio of the mass of an untapped powder sample to its 
volume, including the contribution of the interparticulate void volume. The tapped density, instead, is an 
increased bulk density attained after mechanically tapping a receptacle containing the powder sample 
(Pharmacopoeia, 2014). In this work the bulk density was determined gently pouring 2 g of the sample in a 
graduated cylinder: the ratio between the mass and the volume occupied gave the bulk density. The tapped 
density was determined after a tapping procedure achieved with 100 manual taps, the ratio between the 
sample mass and the tapped volume gave the tapped density. From ρ  and ρ  the HR and CI can be easily 
calculated according to their definitions: HR = ρρCI = 1 − ρρ ∙ 100 (3) 
2.5 Scanning Electron Microscopy (SEM) morphology 

The granules morphology were analyzed with the scanning electron microscope Zeiss DSM 962 (Zeiss, 
Germany). Samples were fixed over an adhesive carbon tab, previously stuck to an aluminum stub and coated 
with gold (layer thickness 250 Å) using a sputter coater (B7341, Agar Scientific, Stansted, UK). All the images 
were taken with a zoom of 300x. 

2.6 Tequil® Multi characterization 

The Tequil® Multi was characterized in terms of dry weight content, using the moisture analyzer MB45 (Ohaus 
Europe, Switzerland). The product showed an amount of dry weight content of 0.6145 gTeq/mLsol that can be 
intended as the concentration of AI in the commercial product.  
The product was characterized spectrometrically using a LAMBDA 35 UV/Vis Systems spectrophotometer  
(PerkinElmer, USA). The samples were analyzed using a previously developed technique (Cascone et al., 
2012) at λ=280 nm. 

3. Results and discussion 
3.1 Particle size distributions 

The PSDs, in terms of cumulative undersize mass distributions (Q ), of GC and GD and a granules picture are 
shown in Figure 1. As it can be seen GC and GD reveal very similar PSDs where the 70% of the granules 
have a mean diameter greater than 0.7 mm. To characterize the PSDs with an average value the median 
diameter (d ) can be used, that is the diameter for which one half of the total mass of particles are larger, and 
one half smaller.  
 
 
 

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Figure 1. Particle size distributions in terms of cumulative undersize mass distributions (left) and granules 
picture (right). 

Therefore, in Figure 1, it is the diameter for which Q = 0.5 that correspond to 1.4 mm for both the granulated 
products. From the graph it can even be seen that approximately the 20% of the particles have a mean 
diameter greater than 2 mm, that correspond to the mesh opening of the sieve used for the milling step. This 
result can be explained considering that the wet granules forced to pass through the sieve acquire an 
elongated shape, leading their mean diameter to be greater than 2 mm. An ultimately consideration, looking at 
Figure 1, can be made on the effectiveness of the wet granulation process carried out in this work in terms of 
particles size enlargement. Indeed the final granules dimensions were far above the initial HPMC powders 
dimensions, defined “fine particles” (10-150 µm), from the producer (Dow, 2000). 

3.2 Granules loading 

The amount of Tequil® Multi encapsulated in the granules were theoretically calculated and experimentally 
quantified. The theoretical amount can be evaluated starting from the quantity of HPMC and Tequil® Multi (in 
mass) employed in the granulation process obtaining the 9% wt/wt and the 33% wt/wt of Tequil® Multi in the 
granules, respectively for GD and GC. The experimental quantification was done dissolving a known amount 
of product in a certain volume of distilled water. The resultant solutions were analyzed spectrometrically and 
the amount of Tequil® Multi quantified. The results gave the 9% wt/wt and the 32% wt/wt for GD and GC 
respectively, validating the quantitative method to analyze the Tequil® Multi described in the paragraph 2.6.  

3.3 Flowability and morphology 

In Table 1 the bulk and tapped densities, HR, CI are reported. To emphasize the granulates results are 
reported in the same table the value obtained with the HPMC powder as well. Looking at the granulate bulk 
and tapped densities it can be seen as GD presents values greater than GC. Considering that both the 
systems have similar PSDs, therefore the same degree of void, the higher bulk and tapped density values can 
be explained only if GD presents higher particle density, therefore more compact granules. The Hausner Ratio 
and Carr’s index depict GD and GC both as “excellent flow granules” whereas the initial HPMC powders have 
very poor flow properties and tend to be cohesive.  

Table 1. Products flowability and flow description. 

 	 ⁄   ⁄   −   −  Flow Description (Nedderman, 2005)
HPMC Powder 333.0 ± 0.0 468.6 ± 6.4 1.41 28.9 Cohesive powders – poor flow 

GC 285.7 ± 0.0 317.5 ± 5.0 1.11 10.02 Free flowing – excellent flow granules 

GD 400.0 ± 0.0 438.0 ± 5.6 1.10 8.68 Free flowing – excellent flow granules 

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Figure 2. SEM pictures at 300x of HPMC powder (a), HPCM granulated with distilled water (b), GC (c) and GD 
(d). 

In Figure 2 are reported the SEM images of HPMC powders (a), HPMC granules obtaining with a wetting 
phase of pure distilled water (b), GC (c) and GD (d). As it can be seen, the morphology of GD can be 
collocated in between the one of HPMC granules and GC. Indeed in the first (Figure 2\b) the single particles of 
HPMC powders (Figure 2\a) are no more recognizable due to a great cohesion between them. On the 
opposite, in GC (Figure 2\c) the single HPMC powders particles are in such a way still identifiable, creating a 
less compact structure with higher internal porosity. Between these two extreme morphologies the one of GD 
(Figure 2\d) can be placed, where are present zones in which the single powders particles are distinguishable 
and zone in which they are not. These granules morphologies well explain the density and mechanical results, 
confirming the more compacted structure of GD with respect to GC. The reason of such a different 
morphology can be explained considering the different composition of the wetting phase employed. The 
distilled water seems to have better binding properties with respect to Tequil® Multi and this behavior is 
emphasized in the comparison between HPCM granules and GC where pure water and pure Tequil® Multi 
were used, respectively. 

4. Conclusions 
In this work an hydrogel-based granular system for controlled release in agriculture has been produced and 
characterized. A commercial liquid phytostrengthener has been encapsulated via wet granulation process in 
HPMC matrices, obtaining a granular product. Two different compositions of the wetting phase have been 
used, one with the pure liquid phytostrengthener and another with a water solution of the phytostrengthener, 
obtaining two different products, namely GC and GD, respectively. These granules have been analyzed in 
terms of particle size distribution using the image analysis method and the results have shown similar 
distribution between them. The granulated products have been investigated in terms of flowability 
characteristics measuring the bulk and tapped densities. The results highlighted the good products flowability, 
highly desirable for the powder handling processes, and underlined a greater GD granules density respect to 
GC. The GD has shown a more compact structure, with less void and better HPMC powders coalescence, 
with respect to GC. The reason of such a different morphology, that in turns is responsible for the differences 
in density, has been attributed to the different composition of the wetting phase. 
In conclusion the controlled release systems developed in this work have shown good flowability 
characteristics, indispensable requirements for the production and commercialization. Further studies will be 
devoted to characterize the release pattern of these HPMC-based granular phytostrengtheners. 

239



Acknowledgments 

This work has been supported in part by Fertenia Srl, Bellizzi (SA), Italy, in part by TECNAGRI-
PSR Campania 2007-2013 Misura 124, and in part by Fondazione Cassa di Risparmio Salernitana (Carisal). 
 
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