Effect of various additives on the properties of the films and coatings derived from hydroxypropyl methylcellulose—A review

Abstract Edible films and coating materials are commonly used as appropriate packaging materials to extend the shelf life of fresh food. Due to all their properties, edible film and coating materials have been received much attention. They are biodegradable, edible, and good barrier against environmental parameters; thereby, they could carry and deliver food additives protecting food quality. Hydroxypropyl methylcellulose (HPMC), a cellulose derivatives, can act as an excellent film‐forming agent for coating food produces. The aim of this study was to provide an overview of the HPMC properties and investigate the effects of various additives on its film‐forming properties, such as rheological behavior, water vapor, and gas permeability, as well as mechanical, optical, antioxidant, and antimicrobial properties, with a focus on the recent progress and outputs, which has been recently published. Hydroxypropyl methylcellulose is prone to be commonly used as an advanced film‐forming and coating materials for the sake of well miscibility with a wide range of organic and inorganic materials. However, this polymer requires further improvements regarding moisture susceptibility and thermal properties.

. Notably, cellulose is more suitable for packing purpose as it is not a thermoplastic polymer, whereas its ester derivatives (methylcellulose [MC], hydroxypropyl methylcellulose [HPMC], hydroxypropyl cellulose [HPC], and ethyl cellulose [EC]) are biodegradable thermoplastic polymers. Hydroxypropyl methylcellulose and MC are soluble in the cold water, but after heating they form a thermally reversible and relatively hard gel by heating process at 50-80°C (Embuscado & Huber, 2009). Hydroxypropyl methylcellulose is odorless, flavorless, transparent, stable, oil-resistant, nontoxic, and edible material with good film-forming properties. It is a nonionic polymer with a linear structure of glucose molecules, in which its matrix is stabilized using hydrogen bonds. Methyl substitution of HPMC is performed using the substitution of free hydroxyl groups of glucose with hydroxypropyl groups (Figure 1). Such modifications tend to improve the cellulose backbone regarding viscosity, solubility, gelation, and film-forming performance. Therefore, HPMC polymer can be used for wider applications such as drug delivery and coating (von Schantz, Schagerlöf, Nordberg Karlsson, & Ohlin, 2014).
Hydroxypropyl methylcellulose has also received GRAS-affirmed approval by Food and Drug Administration (FDA), European Parliament and Council Directive (EU), and Joint Expert Committee on Food Additives (JECFA) (Akhtar et al., 2013;Burdock, 2007;Embuscado & Huber, 2009). Hydroxypropyl methylcellulose film properties are strongly dependent on their linear structure and molecular weight.
Accordingly, Ayrancı, Büyüktaş, and Çetin (1997) reported that with increasing molecular weight of HPMC films, WVP reduced, in which such reduction was constantly happened at HPMC films with a molecular weight higher than 41,000, whereas a similar attempt reported an increment in WVP of MC and HPC with increasing molecular weight (Park, Weller, Vergano, & Testin, 1993). In addition, Otani et al. highlighted that molecular weight is not affected WVP of HPMC films, but substitution degree can significantly change the WVP. It can be explained by changes in polarity caused by methoxyl substitution.
Such changes might be related to nature of chemical structure in different cellulose derivatives because HPMC has higher methyl groups compared with MC and HPC, making HPMC films more hydrophilic (Ayrancı́ et al., 1997). Some reports also mention that increase in molecular weight tends to enhance the WVP of HPC and MC films (Park et al., 1993). There are various additives suitable for improving the HPMC properties such as functional performance (tensile strength or WVP) or new properties (antioxidant or antimicrobial) addition. In some cases, film-forming compounds can be dissolved in water. In addition, some solvents (alcohols and acids) also may be used with water for increasing solubility of film-forming compounds, but prior to application, their safety should be considered. Glycerol and sorbitol are commonly used as a plasticizer to improve flexibility. Furthermore, the emulsifier using is required for uniformly dispersion of some hydrophobic additives in the film. Wax and fat are commonly added to edible coating materials, to maintain the quality of fresh products, and prevent the wrinkling their texture. There are some other substances as nutrient compounds or food additives (such as variety of polymers, fatty acids, colors, antioxidants, and antimicrobial agents), which also can affect properties of the coating films.
The main objectives of this study are to characterize the HPMC properties and provide an overview of the effects of various additives (plasticizers, antimicrobials, and/or antioxidants) on the HPMC film performance. This review paper also considers the modifications and improvements in the HPMC film and its coating properties including the recent progress in that field.

| HPM C FILM CHAR AC TERIS TI C S
Hydroxypropyl methylcellulose film is prepared using homogeneously dispersion of its powder (1%-1.5% w/w) and additives into de-ionized water or water/ethanol solution (80°C), following by deaeration of film solution. As coating application, the food products are either sprayed on or immersed in the film solution. Moreover, cast film in the plate is dried and consequently can be used as a packaging material.

| HPMC solution characteristics (pH, density, zeta potential, and particles size distribution of HPMC molecules)
pH is described as a basic factor for solution property control, which can effect on physicochemical properties of HPMC molecules and F I G U R E 1 Chemical structure of hydroxypropyl methylcellulose and schematic of food and drug protected by HPMC coating containing antioxidant compounds (Source: Ghadermazi Although the increase in the size of the particles in the film solution generally provides the unstable of film solution, it has been reported that the steric stabilization promoted by the particles interfacial adsorption and the high value of the particle z-potential (significantly higher than +30 mV) ensures the stability of the emulsified system (Vargas, Albors, Chiralt, & González-Martínez, 2009).

| Flow behavior of HPMC film (apparent viscosity, shearing stress)
Rheology of biopolymer can control the thickness, uniformity of matrix, and film-forming properties of film. In addition, evaluation of rheological behavior is required for processing and preparation of biopolymers such as shearing rates, filling, pumping, and spraying (García, Pinotti, Martino, & Zaritzky, 2009

| Microscopic structure of the HPMC film
Pure HPMC film has a smooth surface as well as homogeneous and uniform matrix. EO addition during film production results in interaction between EO molecules and hydrophilic groups in the polymer matrix, reducing the polymer-polymer bonds and making nonuniform polymer matrix. Also, some changes in the film surface may occur during film drying process, because oil molecules tend to be accumulated on the film surface (Sánchez-González et al., 2009).
The structure of HPMC film is strongly dependent on the quality of bonds present in the film matrix, which are conducted during drying process. The nonuniform film matrix with delaminate structure is formed in the presence of various phases among polymer matrix ( Figure 2).

| HPMC film thickness
Thickness is the fundamental factor for evaluating the film performance, such as barrier properties with impact on shelf life of coated food materials. The film thickness variations are dependent on the types of incorporated materials into films matrix and preparation procedures. Because of high moisture binding capacity, HPMC film thickness could increase with the glycerol adding. Akhtar et al. (2012) reported that with the addition of water-soluble color compounds extracted from red beet into film solution, due to combined effect of glycerol and betacyanin molecules containing lots of hydrophilic groups, the thickness of HPMC film a gradual but nonsignificant increase . According to Akhtar and Aïder (2018), incorporating glycerol (G), non-electro-activated whey, and electro-activated whey into HPMC solution increased the thickness and moisture content of HPMC films. At lower concentration of non-electro-activated whey and electro-activated whey (1%), there Abbreviation: NR, not reported. a η = apparent viscosity of film dispersions; T = temperature; RH = relative humidity. These environments were equilibrated before analysis. d = thickness; TS = tensile strength; E = elongation; EM = elastic modulus; WVP = water vapor permeability; OP = oxygen permeability. b H = HPMC; SM = sorbitan monostearate; SP = sucrose palmitate; MCC = microcrystalline cellulose; WPI = whey protein isolate; G = glycerol; CS/TPP = chitosan/tripolyphosphate nanoparticles; TTO = tea tree essential oils; N = nisin; BW = beeswax; SA = stearic acid; AA = ascorbic acid; CA = citric acid; GO = ginger essential oil; BO = bergamot essential oils; LO = lemon essential oils; LA = lauric acid; SH = shellac; PEG = polyethylene glycol; LAB = lactic acid bacteria; NRC = natural red color; TP = tapioca starch; CEO = clove essential oil; OEO = oregano essential oil; SEO = sage essential oil; Na-P = amylose-sodium palmitate inclusion complexes; NFC = TEMPO-oxidized nano-fibrillated cellulose; Al 2 O 3 -NPs = aluminum oxide nanoparticles; SiO 2 -NPs = silica oxide nanoparticles.
was no significant change in the film thickness, but at higher concentrations of non-electro-activated whey and electro-activated whey (2%, 3% and 4%), due to film-forming solution contains higher dry matter and less water that is evaporated during the drying process of the films, the thickness of HPMC film significantly increases.

| HPMC film mechanical characteristics
Packaging material with good mechanical properties can protect food items inside the packaging against mechanical and physical stresses. Therefore, to extend the shelf life of food products, mechanical properties are the important properties for packaging materials. The tensile analysis is the method used for evaluating mechanical properties of the film. Tensile strength is defined as the maximum resistance of the film to breaking under tension. The increase in tensile strength can be related to reduction in size of particles and increase in the surface areas. As such, higher surface areas make higher hydrogen bonding between polymer matrix and particles. In addition, the bigger particles interfere in gel formation during drying, resulting in further interaction between particles.
Such phenomena can lead to further hydrogen bonding, thereby enhance the tensile strength of the film. Notably, the tensile strength of such composite films was almost similar to that in polyethylene terephthalate (PET) (Dogan & McHugh, 2007). It is implied that HPMC film with stronger mechanical properties could protect the products because it is crucial that film-forming materials and coatings should be capable to protect products against mechanical stresses. showed less impact of plasticizer on their matrix (Hong, Lee, & Son, 2005). Incorporating different plasticizers such as polyethylene glycol, glycerol, and 1,2-propylene glycol exhibited strong effects on the HPMC and hydroxypropyl starch films properties such as providing lamellar structure and reducing tensile strength as well as increasing crystalline degree and elongation at break of pure HPMC (Zhang et al., 2018). Incorporating glycerol, non-electro-activated whey, and electro-activated whey into HPMC film significantly decreased tensile strength and Young's modulus (Akhtar & Aïder, 2018). Bodini et al. (2019) reported that HPMC reduced the tensile strength of starch as an orally disintegrating film and caused the films to be less mucoadhesive. The orally disintegrating polymers are related to biopolymers that possess desirable properties for controlled-release core compounds for drug delivery and controlled-release active compounds (Dixit & Puthli, 2009). Choi, Singh, and Lee (2016) reported that active HPMC containing oregano and bergamot essential oils exhibited strong physical and mechanical properties.

| Color characteristics of HPMC film
Color is an important film characteristic affecting consumer acceptability when film is applied on food as a wrapper (Klangmuang & Sothornvit, 2016). Naturally, HPMC is a transparent polymer.
Incorporating specific materials into film affects on the film proper-  Akhtar et al. (2013) found that incorporating glycerol into HPMC film relatively reduced the film transparency. Beet red pigments, depending on the added concentration, also could decrease the HPMC film transparency (Akhtar et al., 2013).
Moreover, there was no significant change in color parameters by adding glycerol into the HMPC film . Investigation of two phases of HPMC/ hydroxypropyl starch blends is carried out using dyeing hydroxypropyl starch with iodine method for optical mi- In addition, there may be a binding capacity of nanoclay to the yellow color and beeswax to the white color (Klangmuang & Sothornvit, 2016). Green tea contains some active compounds such as antioxidants, minerals, and vitamins, which can be exploited in food and nutrient industry through a controlled-release system (Cabrera, Artacho, & Giménez, 2006). In an examination, the HPMC film con-

| Oxygen permeability of HPMC film
Gas permeability of HPMC film is affected by various factors, such as temperature, thickness, and environment relative humidity.
Hydroxypropyl methylcellulose films tend to make crosslinks with water by increasing the relative humidity, which can increase the gas transmission rate and make the soft matrix. Hydroxypropyl methylcellulose is a strong film-forming agent, transparent, flexible, and oxygen permeable material with appropriate sensory properties (Miller & Krochta, 1997

| Moisture content and solubility of HPMC film
Solubility is the key factor to determine the use of the film in wide The water absorption of HPMC film decreased with adding the surfactants (e.g., sucrose palmitate and sorbitan monostearate) because of the increasing HLB value and as hydrophilic compounds can interact with HPMC film matrix as a result of the low surface tension in the film matrix (hydrophilic-lipophilic balance). This reduction is attributed to hydrogen bonds between hydroxyl groups of surfactants and film matrix, which can reduce available active sites for bonding with water molecules (Villalobos, Hernández-Muñoz, & Chiralt, 2006). Compounds with high hydroxyl groups can interact with active groups among the film matrix and reduce the film water absorption capacity. The HPMC film containing polyethylene glycol showed less water absorption capacity compared with polyvinyl alcohol (Okhamafe & York, 1983).
The moisture level of film is dependent on surfactants contents and its chemical structure. With increasing polarity of the surfactant, moisture of HPMC film reduced as a result of the interaction Hydroxypropyl methylcellulose films containing the highest surfactant concentration exhibited the highest moisture barrier (Villalobos et al., 2006). The moisture and water vapor permeability of HPMC film reduced via adding ethanolic gum. Because of further water molecules binding, film matrix swelled and became softer, resulting in reduction in polymer density and displacing the polymer chains (Pastor et al., 2010). The moisture content of HPMC film can increase with increasing the relative humidity of environment. This phenomenon firstly occurs slowly but increases gradually to reach the highest rate.
Plasticizer like glycerol also can enhance the film moisture content because of hydrogen bonding between plasticizer molecules and polymer chain, resulting in additional space between the polymer chains for water absorption. Beet red pigment added to the film tends to interact with water molecules via hydroxyl groups, which can increase the moisture content of HPMC film (Akhtar et al., 2013). As shown in Figure 5, HPMC can be dissolved in a wide range of solutions, and the addition of complexed sodium palmitate ligands (Na-palm) into HPMC film remarkably reduced its solubility, which HPMC/Na-palm became insoluble in both in the acidic (pH = 4) and pH of 7. The solubility of HPMC/Na-palm in the higher pH (10) significantly increase (Hay et al., 2018). There is no significant change in solubility of the HPMC film containing nanoparticle with pure HPMC film (Osman et al., 2019).

| Water vapor permeability (WVP) of HPMC film
Water vapor permeability of HPMC film is being progressive because shelf life of coated food produces and preservation of dry food materials against fungi growth are strongly dependant on WVP of film.
Water vapor permeability is adversely contributed to HPMC film performance. Therefore, incorporating hydrophilic compounds such as fatty acids, waxes, surfactants, and resins into the polymer are commonly used to overcome this drawback (Miller & Krochta, 1997).
Hydroxypropyl methylcellulose film exhibited less WVP compared with cellophane (Villalobos et al., 2006). On the other hand, when high WVP is required, the high permeability can be an appropriate property. Incorporating hydrophobic compounds such as fats, shellacs, resins, EOs, emulsifiers, and surfactants into HPMC film reduced WVP, whereas such compounds led to an increase in brittleness and fragility. Therefore, hydrophobic compounds can be incorporated into film matrix or can be used separately on the polysaccharide and protein film. The authors were not reported any significant change in the WVP by the addition of microcrystalline cellulose particles into HPMC film (Dogan & McHugh, 2007). Water vapor permeability of film significantly varies depending on the relative humidity of environment and ambient temperature (Pastor et al., 2010). The WVP of film is strongly dependant on the solubility and hydrophilicity of plasticizers or pigment compounds. The plasticizer is a low molecular weight compound, which tends to reduce the intermolecular forces between polymer chains. The plasticizer can also reinforce flexibility, elongation, and toughness of the film matrix.
In general, addition of the glycerol into polymer can increase WVP. Laboulfie, Hemati, Lamure, and Diguet (2013) reported that introducing glycerol into HPMC film increased the WVP of film. Glycerol can significantly change the film properties such as reducing density and increasing WVP. Moreover, due to the presence of the polar hydroxyl groups, glycerol can reinforce the interaction between the polymer surface and the water molecules . Water vapor permeability of MC film could be increased up to double with incorporating 50% (w/w) glycerol (Imran, El-Fahmy, Revol-Junelles, & Desobry, 2010). Addition of plasticizer and beet red pigment into the film can increase WVP as a result of lower intensity of intermolecular bonds between polymer chains and reduction in the density of polymer matrix, so that the films have higher quality of mobility and additional transmission pathways among matrix.
Hydroxypropyl methylcellulose film shows higher WVP in the higher relative humidity because water molecules can interact with F I G U R E 5 Solubility of the blending HPMC/Na-Palm films soaked for 2 hr at pH 4, 7, and 10. A: 100% HPMC film, B: 75/25% HPMC/Na-Palm film, C: 50/50% HPMC/Na-Palm film, D: 25/75% HPMC/Na-Palm film (Source: Hay et al., 2018) hydrophilic groups among film and act as plasticizer (Akhtar et al., 2013). Hydrophilic films tend to interact with water molecules, which can increase the films softness. Therefore, to evaluate the precise solubility and water vapor barrier of film, relative humidity of environment should be controlled. The amount of water vapor molecules absorbed by film matrix is attributed to the morphological and chemical structure of the HPMC film.
Water vapor permeability of HPMC film could be enhanced with increasing surfactants content. Addition of the beeswax into film reduced the WVP. The formula (WVP = 7.3e −0.014X ) has been presented for calculating the WVP. Accordingly, the effects of different beeswax contents on the barrier properties of the film can be precisely calculated (WVP is evaluated in mm/KPa hr m 2 , where X is a concentration of beeswax among film) (Navarro-Tarazaga et al., 2011).
With incorporating 0.5% (w/w) of shellac into HPMC film, WVP decreased (11%), while this reduction increased with increasing shellac content (Byun, Ward, & Whiteside, 2012). Introducing EOs extracted from ginger into HPMC film reinforced water vapor barrier at lower temperature, comparing with higher temperature. It may be attributed to higher movement of EOs molecules toward the film surface and forming nonuniform film matrix, resulting in lower barrier properties (Atarés, Pérez-Masiá, & Chiralt, 2011). Furthermore, with EOs content increase, WVP of HPMC and chitosan films reduces (Ghadermazi et al., 2016;. Water vapor permeability of film is dependent on various factors such as temperature, relative humidity, film components, and thickness. Accordingly, high permeable HPMC film is associated with its long and hydrophilic chains (Sánchez-González et al., 2009). (2,2,6,6tetramethylpiperidin-1-yl)oxyl or (2,2,6,6-tetramethylpiperidin-1-yl) oxidanyl, commonly known as TEMPO. Introducing TEMPO-oxidized nano-fibrillated cellulose into HPMC film improves mechanical, thermochemical, and moisture barrier properties of film (Hassan, Fadel, & Hassan, 2018). Incorporation of zein nanoparticles into HPMC film decreases the WVP of film (10%-30%) (Bodini et al., 2019). Hay et al. (2018) reported that introducing novel amylose-sodium palmitate inclusion complexes into HPMC improve the barrier properties including low water and oxygen permeability in the film without any deterioration effects on the physical properties. As result the HPMC film shows lower water uptake and moisture content as well as higher thermal stability. SiO 2 -NPs led to increasing in the WVP, CO 2 permeability, tensile, and oxygen transmission rate (OTR). It can be explained that (a) SiO 2 -NPs as filler occupy the pore in the HPMC matrix, (b) HPMC and SiO 2 -NPs can make a coherent and uniform structure, and (c) glycerol also can reduce water evaporation (Osman et al., 2019). Incorporating glycerol, non-electro-activated whey, and electro-activated whey into HPMC film significantly decreased the WVP (Akhtar & Aïder, 2018). It has been reported that oregano EO nanoemulsion reduced the WVP, indicating higher barrier properties in the HPMC film (Lee et al., 2019).

| Thermal properties of HPMC film
Thermal properties of material can provide the information regarding degradation and decomposition of materials during heating process as well as effects of residue (degraded compounds) on the quality of materials. Therefore, thermal stability data are required for preparation, processing, and storage of materials (Rowe, 2002).
Hydroxypropyl methylcellulose particles aggregate at approximately 80°C and with decreasing temperature dissolve again.
Differential scanning calorimetry (DSC) analysis is commonly used for determining the glass transition temperature (T g ) of materials.
The glass transition temperature is the temperature region where the polymer changes from a hard and glassy material to a soft and rubbery material. The T g of HPMC film is 150.53°C. Because of additional transmission pathways and spaces caused by plasticizers, T g was decreased via adding the glycerol. Incorporating phenolic Betacyanins pigment decreased T g of HPMC film due to the presence of higher hydrogen bonds between phenolic compounds and film matrix (Akhtar et al., 2013).

| Antioxidative properties of HPMC film
Oxidation of food can lead to off-flavor, nutrients decomposition, or toxic material production, resulting in lower consumer-acceptability.
To protect the food items from oxidation, delivering the antioxidants using biocompatible materials is still interested (Choe & Min, 2009).
Edible film can be used as food antioxidants carrier and deliver them as active agents, protecting food from oxidation. Ascorbic acid, citric acid, almond oil, and EOs extracted from ginger can improve the antioxidant activity of HPMC film (Atarés et al., 2011). In addition, the shelf life of soybean oil can be significantly extended if it is packed in the HPMC films containing clove, oregano, and sage EOs (see Figure 1) (Ghadermazi et al., 2016 (Phoopuritham, Thongngam, Yoksan, & Suppakul, 2012). Oxidation process of salmon oil packed in HPMC containing yellow and red colors (edible color) was significantly lower compared with salmon oil packed in HPMC containing blue and green colors. It may be explained that the former colors act as light block agents (dark condition) and the latter colors act as transparent film (Akhtar et al., 2010). Natural colors such as beet and carrot also act as light-blocking agents in the HPMC film, resulting in higher antioxidant property . Rhimi et al. (2018) find that with increasing cypress seed extract concentration, water vapor barrier, opacity, and antioxidant capacity of HPMC film increased. Hydroxypropyl methylcellulose film containing 2% of cypress seed extract showed lowest oxidation degree during storage. Because of highest active phenolic/flavonoid contents, HPMC film containing 2% of cypress seed extract showed a good light barrier, resulting in a decrease in the olive oxidation (Rhimi et al., 2018).

| Antimicrobial properties of HPMC film
Fresh food materials are prone to lose quality because of continuously physical, chemical, and microbial reactions. Such reactions may lead to foodborne disease, which can negatively impact on safety, sensory, and nutrients of foodstuffs. To prolong the shelf life of fresh food items by controlling microbial growth, protective coating using biopolymers is an effective method. The coating method can be used for agriculture products, meat, and dairy products (Cha & Chinnan, 2004

| CON CLUS IONS
Hydroxypropyl methylcellulose is an edible film with strong functional properties and an applicable film-forming agent. This film is transparent, odorless, flavorless, chemically stable, biodegradable, and nontoxic, which can extend the shelf life of fresh food products. Hydroxypropyl methylcellulose film is also a good oxygen barrier and oil-resistant film, but HPMC film is still required further improvements regarding WVP because HPMC film is described as a high hydrophilic compound. The numerous attempts are being F I G U R E 6 Inhibition zone of blends active films against bacteria of food origin F1 = HPMC film, F6 = HPMC + 10 4 IU Nisaplin®, F9 = HPMC + 30% glycerol + 10 4 IU Nisaplin,® F10 = HPMC + 50% glycerol + 10 4 IU Nisaplin® (Source: Imran et al., 2010) advanced to improve the WVP of HPMC film. Wax, beeswax, and organic EOs were added to HPMC to overcome WVP drawbacks.
To improve the elasticity of HPMC film, various plasticizers such as glycerol and sorbitol are commonly used. Such compounds can enhance the elongation at break and permeability and may lead to tensile strength reduction. Antioxidant activity of HPMC film can be significantly improved using a wide range of compounds such as EOs, synthesized antioxidants, color compounds, and organic extracts. Furthermore, HPMC film is incorporated with various lipids to reduce the fruits weight loss and keep the fruits sensory properties (or quality). Hydroxypropyl methylcellulose film also can significantly extend the shelf life of fresh products by providing a modified atmosphere through the selective gas permeability without any adverse effects on the fruit sensory quality. Despite HPMC is not a strong biocidal polymer, this polymer is sufficiently miscible to be incorporated with organic and inorganic antimicrobial agents.
Hydroxypropyl methylcellulose films and coatings containing antimicrobial agents have strong antimicrobial efficacy against grampositive/and gram-negative bacteria as well as fungi. Hydroxypropyl methylcellulose film properties are strongly dependant on various factors such as relative humidity, temperature, thickness, production method, type, and ratio of materials incorporated into films.
Among environmental parameters, relative humidity has the most significant role in the film performance and control of it is crucial for the HPMC film quality. As a functional biopolymer, HPMC is prone to be used in wider applications upon addressing the shortcomings involved with its performance. Accordingly, addition of silica-based materials could overcome the humidity susceptibility, thermal, and mechanical imperfectness. Therefore, the upcoming attempts should be dealing with modification of physical properties of HPMC based on the expected purposes.

ACK N OWLED G M ENT
The authors received no financial support for this study.

CO N FLI C T O F I NTE R E S T
The authors declare that they do not have any conflict of interest.

E TH I C A L A PPROVA L
This study does not involve any human or animal testing.