Pineapple-Derived Sodium Carboxymethylcellulose: Physicochemical Basis for Hydrogel Formulation

Abstract

The synthesis of sodium carboxymethylcellulose (NaCMC) from lignocellulosic pineapple stubble provides a renewable alternative to conventional cellulose sources for pharmaceutical applications. This study aimed to obtain NaCMC from pineapple biomass, characterize it according to pharmacopoeial specifications, and formulate hydrogels as a physicochemical proof-of-concept for future drug delivery and tissue regeneration applications. NaCMC was successfully synthesized and met the requirements of the Mexican Pharmacopoeia. Hydrogels were prepared by blending NaCMC with gelatin and crosslinking with citric acid. Spectroscopic, morphological, and thermal analyses confirmed the structural equivalence between pineapple-derived NaCMC (NaCMC-Pi) and commercial NaCMC (NaCMC-Co). Swelling and gel fraction studies showed that NaCMC-Pi hydrogels exhibited a higher gel fraction, indicating a more crosslinked network, which corresponded to lower swelling capacity but higher thermal stability compared to NaCMC-Co hydrogels. Overall, these results demonstrate that pineapple stubble is a viable source of pharmaceutical-grade NaCMC and that the resulting hydrogels provide a robust physicochemical basis for future biomedical validation. The use of agro-industrial residues additionally offers a complementary sustainability benefit without compromising pharmaceutical performance.

1. Introduction

Sodium carboxymethylcellulose (NaCMC) is one of the most widely studied cellulose ethers due to its versatility in industrial applications, particularly in pharmaceutical technology, where it serves as a binder, stabilizer, and release-modifying excipient [1,2,3,4]. In addition to pharmaceutical products, NaCMC has gained relevance in the food and cosmetics industries, largely because of its hygroscopic nature, viscosity in dilute solutions, protective colloidal behavior, ability to form stable films and adhesives, and properties that determine its various uses, including wound dressings, controlled-release systems, and thickening agents [5,6]. In the pharmaceutical context, NaCMC is particularly valuable as an excipient in various dosage forms, as it promotes controlled drug release and improves formulation stability [7].

Building on these applications, recent research has emphasized sustainable synthesis routes for NaCMC, particularly its production from lignocellulosic biomass through alkali activation and etherification with monochloroacetic acid—methods that not only ensure high degrees of substitution but also reduce its environmental impact [7,8,9]. As a cellulose derivative, NaCMC can be synthesized from lignocellulosic stubble, which is an abundant and renewable source of biopolymers [10]. Cellulose, the primary structural component of plant biomass, continues to attract the interest of researchers because of its biosynthetic mechanisms, functional versatility, and wide applicability in advanced materials [11].

Pineapple (Ananas comosus) is a tropical fruit appreciated worldwide for its distinctive flavor and nutritional content, as it is rich in vitamins, minerals, and bioactive compounds [12]. Mexico is one of the leading producers of pineapple, with crops concentrated in Veracruz, Oaxaca, Nayarit, and Tabasco [13,14]. This aligns with global trends in sustainable agricultural innovation and biomass valorization reported by the FAO [14]. However, its cultivation and processing generate large volumes of stubble, such as crowns, peels, cores, and postharvest stubble. This stubble, which is predominantly lignocellulosic in composition, presents a sustainable alternative for value-added applications such as textiles, paper, biofuels, enzymes, and, more recently, biomaterials [8]. The high cellulose content of pineapple straw makes it a promising raw material for the synthesis of NaCMC, as demonstrated in recent studies on the carboxymethylation of pineapple leaf fibers [9,12], thereby transforming agricultural stubble into functional products with pharmaceutical relevance.

One of the most innovative applications of NaCMC derived from renewable sources is its incorporation into hydrogel systems for tissue engineering and drug delivery, where its biocompatibility and tunable chemical functionality enable the design of versatile biomaterials [6,11]. Polymeric hydrogels have gained increasing attention as matrices for drug delivery and regenerative medicine because of their three-dimensional structure, ability to absorb water many times their own weight, and mechanical properties that can be adapted for biomedical applications [15]. These hydrogels not only allow for sustained therapeutic release but also promote tissue healing, positioning them as clinically valuable alternatives in wound treatment [12]. Previous work by our group also reported the development of biomaterials based on biopolymer hydrogels with potential biomedical applications, reinforcing the feasibility of these systems for tissue engineering and controlled release [16]. In this context, NaCMC-based hydrogels combine biocompatibility, swelling capacity, and modifiable cross-linking, with the added advantage of being obtained from renewable lignocellulosic sources [14].

Sustainability principles were integrated as an added value in the synthesis and formulation of pharmaceutical biomaterials. The use of pineapple stubble as a renewable raw material aligns with the 12 Principles of Green Chemistry [17,18,19], supporting cleaner production and responsible innovation. To reinforce this approach, environmental indicators such as the E-factor—proposed by Sheldon to quantify process waste—and energy demand estimates were considered to evaluate the environmental efficiency of the process. These parameters contribute to the integration of green metrics into circular bioeconomy frameworks [20,21].

Therefore, this study aimed to demonstrate, as a proof of concept, the synthesis of sodium carboxymethylcellulose from Ananas comosus stubble, its characterization according to pharmacopoeial specifications, and the development of a hydrogel formulation with physicochemical properties suitable for pharmaceutical applications. While biological validation (e.g., cytotoxicity and biocompatibility assays) was not included in this phase, the work establishes the physicochemical foundation for future biomedical studies. In doing so, the study contributes to the sustainable revalorization of agro-industrial biomass and advances the use of biopolymer-based systems for drug delivery.

2. Materials and Methods

2.1. Materials

Plant material and pretreatment: Pineapple stubble (Ananas comosus, Cayena variety), collected in Ciudad Isla, Veracruz, was washed and milled Quaker City Philadelphia model 4-E, (Quaker City Mill, Philadelphia, PA, USA) and dried at 60 °C for 12 h. Reagents: Cellulose extraction and NaCMC synthesis: Sodium hydroxide (97–100.5%, J.T. Baker, Avantor, Phillipsburg, NJ, USA); hydrogen peroxide (50%, BIOSACHEM, Tepotzotlán Estado de México, México); monochloroacetic acid (99%, Sigma—Aldrich, St. Louis, MO, USA); isopropyl alcohol (99.5%, Karal S.A. de C.V., Guanajuato, México); methanol RA (99.8%, Tecsiquim, Mexico City, México); acetic acid (99.7%, J.T. Baker, Phillipsburg, NJ, USA); ethanol (99%, Química Meyer, Mexico City, México); and deionized water. Hydrogel formation: Citric acid (99.9%, Karal S.A. de C.V., Guanajuato, México); gelatin (food-grade, Duche S.A. de C.V., Mexico City, México); and sodium carboxymethylcellulose (Gelycel F1 4000, Amtex Corp, Mexico City, México). Physicochemical tests included methylene blue (Hycel de México, Naucalpan, Mexico.), α-naphthol (100%, Supelco, Bellefonte, PA, USA), sulfuric acid (95–97%, Supelco, Bellefonte, PA, USA), m-cresol purple (Supelco, Bellefonte, PA, USA), and hydrochloric acid (36.5–38%, J.T. Baker, Phillipsburg, NJ, USA).

2.2. Methodology

2.2.1. Cellulose Obtained

The dried pineapple fibers (Ananas comosus) were suspended in deionized water at a ratio of 1 g per 2 mL (1:2 w/v) and subjected to thermal pretreatment in an autoclave at 121 °C for 10 min. After cooling, the excess water was removed, and the fibers were treated with 200 mL of 2 M NaOH at 121 °C for 60 min to remove hemicellulose and lignin (model CVQ-B35L Ecoshel, Pharr, TX, USA). The resulting material was washed repeatedly with deionized water until a neutral pH was reached.

For bleaching, the fibers were immersed in 750 mL of 20% hydrogen peroxide under constant agitation and heating on a hot plate at the boiling temperature of hydrogen peroxide for 5 h. Finally, the bleached material was thoroughly washed with deionized water, drained, and dried at 60 °C for 12 h to obtain purified cellulose fibers (Drying oven, model 9023A, Ecoshel, Pharr, TX, USA). The complete process and the final cellulose obtained are shown in Figure 1. This procedure follows the widely described alkaline and oxidative treatment protocols for the isolation of cellulose from lignocellulosic stubble [22,23,24].

2.2.2. Synthesis of Sodium Carboxymethylcellulose (NaCMC)

The cellulosic fibers (5 g) were suspended in 140 mL of isopropyl alcohol and subjected to vigorous stirring for 15 min. Subsequently, 10 mL of 40% NaOH solution was added dropwise over 30 min, and the mixture was maintained under continuous stirring for 1 h. Monochloroacetic acid (7 g) was then added to small portions over 30 min, and the reaction mixture was kept at 55 °C for 5 h.

After the reaction, the product was filtered, and the solid fraction was suspended in 300 mL of 70% methanol and neutralized with 90% acetic acid. The suspension was vacuum filtered, washed with 70% ethanol under vigorous stirring, allowed to rest for 10 min, and filtered again. This washing procedure was repeated six times, followed by a final wash with 100 mL of absolute methanol. The recovered material was dried at 60 °C for 12 h. This etherification process via alkali activation followed by monochloroacetic acid substitution [25,26] aligns with contemporary high-purity NaCMC synthesis methodologies utilizing organic solvents and alcohol media to minimize side reactions and increase product purity [8,27].

2.2.3. Average Molecular Weight of Sodium Carboxymethylcellulose

Intrinsic viscosity measurements of NaCMC solutions (dissolved in 0.01 M NaCl at concentrations of 2.00, 1.60, 0.96, 0.64, and 0.32 g/dL) were performed using an Ostwald viscometer. The zero-concentration limit of reduced viscosity was extrapolated to obtain the intrinsic viscosity ([η]). The viscosity-average molecular weight (Mᵥ) was then determined using the Mark–Houwink method [28], Equation (1) [29,30,31]:

$$\left[\eta \right]=K{M}^a$$

(1)

where K and a are constants specific to the polymer–solvent system. Based on systematic studies of NaCMC in 0.01 M NaCl, the exponent was identified as a = 0.92 and K = 0.81 × 10⁻³ cm g⁻¹, supporting the semiflexible polymer behavior characteristic of NaCMC [29,31]. Recent advances also reinforce the precision of viscometry approaches in estimating molecular weight distributions for carboxymethylcellulose derivatives [32].

2.2.4. Fourier Transform Infrared (FTIR) Spectroscopy

FTIR spectroscopy (Perkin Elmer Inc., Waltham, MA, USA) was employed to identify functional groups and confirm the chemical modification of NaCMC and the hydrogels, as previously described by Dardeer H. et al. [33]. Analyses were performed in the range of 4000–650 cm⁻¹, and samples were directly placed on the measuring plate without additional treatment.

2.2.5. Physicochemical Characterization of Sodium Carboxymethylcellulose

The physicochemical properties of the synthesized NaCMC were evaluated following the procedures described in the Pharmacopoeia of the United Mexican States (FEUM, Mexico City, México) [34]. The tests performed included macroscopic description, solubility, identification tests, pH determination, degree of substitution, loss on drying, and residue on ignition.

2.2.6. Hydrogel Synthesis

The hydrogels were formulated on the basis of a modified version of the NaCMC-gelatin gelation strategy in which citric acid was used as a crosslinker. A 1% (w/v) sodium carboxymethyl cellulose solution was prepared in deionized water and mixed with a 4% (w/v) gelatin solution, achieving a weight ratio of 75:25 (NaCMC: gelatin). To induce cross-linking, citric acid was added at 25% (w/w) relative to total solids.

The mixture was heated at 80 °C for 2 h (Drying oven, model 9023A, Ecoshel, Pharr, TX, USA) to activate esterification between the hydroxyl groups of NaCMC, gelatin, and citric acid, resulting in the formation of a crosslinked network. The obtained hydrogel was dried in an oven at 40 °C for 4 h to remove excess moisture. After manual separation, the hydrogels were washed with deionized water to remove unreacted reagents, and drying was performed at 40 °C for 3 h until a constant weight was reached. The selected protocol is consistent with similar NaCMC-based hydrogel systems crosslinked with citric acid [35,36].

2.2.7. Scanning Electron Microscopy (SEM) Studies

The hydrogel samples were freeze-dried for 36 h (Freeze-dryer GJ-10, Guangzhou Jingchuang Scientific Instrument Co., Ltd., Guangzhou, China), mounted on supports with carbon tape, sputter-coated with gold (sputter coater Quorum Q150RS, Quorum Technologies Ltd., Lewes, UK), and examined by SEM (SU3500, Hitachi High-Tech Corporation, Tokyo, Japan) to assess the pore architecture and surface morphology. The micrographs revealed interconnected porous networks characteristic of crosslinked NaCMC hydrogels, which agrees with recent reports on pore morphology in biopolymer hydrogels via SEM analysis [37].

2.2.8. Thermal Analysis (DSC and TGA) Studies

Thermal stability and phase transitions were studied via thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), as described by Capanema N. et al. [35]. Samples of 10 mg were analyzed under a temperature ramp of 10 °C/min over a range of 0–800 °C (DSC/TGA analyzer SDT Q600 V20.9, TA Instruments, New Castle, DE, USA).

2.2.9. Swelling Degree and Gel Fraction Tests

The swelling capacity of the hydrogels was determined to evaluate their cross-linking efficiency. Experiments were conducted in triplicate using hydrogel samples of approximately 2 cm × 2 cm, with a dry weight between 300 and 400 mg and a thickness below 1 mm. Each sample was immersed in 20 mL of deionized water at room temperature, with measurements taken every 30 min during the first 4 h, at 10 h, and every 24 h thereafter. The degree of swelling (SD%) was calculated as the percentage increase in weight relative to the initial dry weight of the sample, according to Equation (2).

$$SD\%={\displaystyle \frac{W_s-W_o}{W_o}}\times 100\mathrm{\%}$$

(2)

where $W_s$ is the weight of the swollen hydrogel at equilibrium, and $W_o$ is the initial dry weight of the sample.

For gel fraction determination, samples were immersed in water for 24 h, dried to a constant weight, and calculated according to Equation (3), which is based on a previously reported method [35].

$$GF\%={\displaystyle \frac{W_o-W_f}{W_o}}\times 100\mathrm{\%}$$

(3)

where $W_f$ is the final dry weight of the sample after immersion and drying, and $W_o$ is the initial dry weight before immersion.

2.2.10. Environmental Metrics and Process Sustainability Assessment

As part of the sustainable process design, inputs, thermal conditions, and energy consumption were recorded for each stage of cellulose extraction and NaCMC synthesis. Alkaline hydrolysis of raw pineapple stubble fiber was carried out with 2 M NaOH to remove hemicellulose and lignin compounds, facilitating conversion to purified cellulose. The effluents generated were neutralized by successive washings with deionized water until a pH of 7 was reached, minimizing the risk of secondary contamination and complying with the principle of waste prevention [19,38].

In the bleaching stage, 20% hydrogen peroxide (H₂O₂) was used as an oxidizing agent, replacing conventional methods based on sodium sulfide. The use of peroxide represents a safer and more environmentally friendly alternative, in line with the principles of less hazardous synthesis and benign product design [39]. This approach has been supported by recent studies promoting eco-friendly methods for cellulose modification [38,40].

The yield of each stage of the process (raw fiber and purified cellulose) was determined by the ratio between the dry mass of the product obtained (m_product) and the dry mass of the starting material (m_initial), according to the Equation (4):

$$\mathrm{R}\mathrm{\%}={\displaystyle \frac{m_{\mathrm{p}\mathrm{r}\mathrm{o}\mathrm{d}\mathrm{u}\mathrm{c}\mathrm{t}}}{m_{\mathrm{i}\mathrm{n}\mathrm{i}\mathrm{t}\mathrm{i}\mathrm{a}\mathrm{l}}}}\times 100$$

(4)

Energy consumption was estimated from the nominal power (kWh) and operating time of the drying, grinding, and reaction equipment, allowing the total energy demand and process productivity to be correlated [41]. Recent studies on energy efficiency in cellulose extraction and modification support this approach [42,43].

The E-factor [21] of the process was calculated using Equation (5):

$$E={\displaystyle \frac{m_{waste}}{m_{\mathrm{p}\mathrm{r}\mathrm{o}\mathrm{d}\mathrm{u}\mathrm{c}\mathrm{t}}}}$$

(5)

where m_waste represents non-recoverable by-products and m_product represents dry NaCMC. This parameter provides a measure of overall material efficiency, enabling comparison with other green synthesis processes for cellulose derivatives [44,45]. Although solvent recovery was not implemented in this study, the experimental design allows its future integration through rotary evaporation systems, which would considerably reduce waste generation and enhance the environmental efficiency of the process [46,47].

3. Results and Discussion

3.1. Synthesis of Sodium Carboxymethylcellulose

3.1.1. Molecular Weight Determination

The average molecular weight of sodium carboxymethylcellulose (NaCMC-Pi) obtained from pineapple stubble was 131,768 g·mol⁻¹. This value was derived from the experimentally determined intrinsic viscosity [η] = 0.4149 dL·g⁻¹, which is consistent with ranges (0.3–0.6 dL·g⁻¹) reported for cellulose derivatives in dilute solution [48]. In the context of hydrogel design, relatively low molecular weight is advantageous for several reasons. First, NaCMC-Pi solutions with a lower molecular weight have a lower viscosity at concentrations relevant to the formulation, which facilitates rapid wetting and dissolution, improves mixing with crosslinkers, and promotes uniform network formation during crosslinking with citric acid [35,49]. Second, once gelled, networks prepared from lower-molecular-weight polysaccharide chains can achieve better swelling properties and mechanical response at a given crosslinker/solids ratio, characteristics that are desirable for exudate management and adaptability in wound dressings [49,50,51]. Third, the relatively short chains of NaCMC-Pi reduce chain entanglement and steric hindrance, which improves solute diffusion through the hydrogel matrix and may allow sustained but efficient drug transport for localized administration [3,4,5]. These characteristics are consistent with recent reports on NaCMC-based hydrogels for wound care and drug delivery, in which formulation strategies leverage viscosity (an indicator of molecular weight) to balance processability, swelling control, and therapeutic release [36,49].

3.1.2. FTIR Analysis of NaCMC Samples

The infrared spectrum of the synthesized NaCMC-Pi (Figure 1) shows the characteristic vibration modes of carboxymethylated cellulose. The broad band centered at 3400 cm⁻¹ corresponds to O–H stretching vibrations, reflecting the extensive hydrogen bonding network of polysaccharides. The absorption at 2900 cm⁻¹ is attributed to aliphatic C–H stretching, consistent with cellulose derivatives described in recent spectroscopic studies. A distinctive band at 1640 cm⁻¹ confirms the presence of C=O stretching vibrations, typically associated with residual carboxyl groups introduced during etherification. In addition, asymmetric (1452 cm⁻¹) and symmetric (1379 cm⁻¹) stretching bands of the carboxylate anion (–COO⁻Na⁺) are observed, both diagnostic signals of NaCMC and indicative of effective carboxymethyl substitution. Finally, the band at 1070 cm⁻¹ corresponds to C–O–C stretching within the anhydroglucose unit, confirming the integrity of the polysaccharide backbone [52].

Compared with the reference spectrum of commercial NaCMC-Co, which is included in the same figure, the high similarity between all bands confirms that the synthesized product from pineapple stubble structurally corresponds to NaCMC. Minor variations in band intensity can be attributed to differences in crystallinity and source material, but no significant structural discrepancies were detected. This agreement is in line with recent work demonstrating that FTIR is a reliable tool for confirming substitution patterns and equivalence between biopolymer derivative [52,53,54,55].

3.1.3. Physicochemical Characterization

The physicochemical evaluation of NaCMC-Pi synthesized from pineapple stubble demonstrated full compliance with the requirements established in the Pharmacopoeia of the United Mexican States (FEUM) (

Table 1. Results obtained from physicochemical tests according to FEUM [34].

Test	Specification	Result
Description	White or grayish white powder.	Complies
Solubility	Solubility Sparingly soluble in water Almost insoluble in alcohol, diethyl ether and other organic solvents.	Complies
Identity tests	A. Sample absorbs methylene blue and sediments as a blue fibrous mass.	Compies
	B. A purplish red color forms at the interface.	Complies
pH	Between 5.0 and 7.0	6.5
Degree of substitution	Between 0.60 and 0.85	0.77
Loss on drying	Not more than 10.0% of its weight	8.1%
Residue on ignition	Between 14.0% and 28.0%, calculated on dry basis	16.3%

). This confirms that the material obtained from agroindustrial waste is of the necessary quality to be considered a pharmaceutical excipient.

Particularly relevant is the degree of substitution (DS), determined as 0.77, which is within the pharmacopeial range (0.60–0.85). This value is associated with favorable solubility in aqueous media and suitable viscosity, properties that are essential for NaCMC to function effectively as a binder, stabilizer, or controlled-release agent in pharmaceutical formulations. Moreover, the loss during drying (8.1%) was less than the maximum allowed (10%), indicating low hygroscopic retention and good stability during storage. The residue on ignition (16.3%) also complied with the specifications, reflecting a low content of inorganic impurities and confirming the efficiency of the purification process.

Taken together, these results highlight that NaCMC obtained from pineapple stubble not only meets pharmacopeial standards but also offers a sustainable alternative to conventional sources of cellulose, supporting its potential for incorporation into pharmaceutical applications without compromising quality.

3.2. Synthesis Process of the Sodium Carboxymethylcellulose Hydrogel

The formation of NaCMC–gelatin hydrogels crosslinked with citric acid (Figure 2) confirms the efficiency of esterification in generating stable three-dimensional polymeric networks. Comparable studies have reported that citric acid enhances hydrogel swelling, mechanical integrity, and biocompatibility, supporting its role as a safe and multifunctional crosslinker [5,35]. The novelty of this work lies in demonstrating that NaCMC derived from pineapple stubble can be successfully employed as a precursor, thus adding a sustainability dimension compared with systems prepared with commercial NaCMC, highlighting the potential of biomass-derived hydrogels for pharmaceutical and biomedical applications [35,36]. At the molecular level, crosslinking occurs mainly through two complementary mechanisms: (i) esterification of the carboxyl groups (–COOH) of citric acid with the hydroxyl groups (–OH) of NaCMC and gelatin, which establishes covalent bonds within the network [35]; and (ii) the reaction of citric acid anhydride intermediates with free amino groups (–NH₂) of gelatin, forming amide linkages (Gel–NH–CO–AC–) that further reinforce the hydrogel structure [56].

3.2.1. Infrared Spectroscopy Characterization of the Hydrogels

As shown in Figure 2, the FTIR spectra of the hydrogels synthesized from NaCMC (NaCMC-Pi and NaCMC-Co) with gelatin and citric acid retain the characteristic bands described above for NaCMC, including the broad O–H stretch (3400 cm⁻¹), C–H (2923–2900 cm⁻¹), C=O stretching (1640 cm⁻¹), and carboxylate vibrations (1452 and 1379 cm⁻¹). In addition, signals related to gelatin proteins, such as amide I (1635 cm⁻¹), amide II (1530 cm⁻¹), and amide III (1239 cm⁻¹), confirm their incorporation into the polymer network [57,58].

No significant spectral differences were observed between the hydrogels prepared with NaCMC-Pi and NaCMC-Co, indicating structural equivalence between the two sources of NaCMC. Minor variations in band intensity reflect differences in molecular organization, but the preservation of functional groups and diagnostic signals confirms effective crosslinking. This result is consistent with recent reports in which FTIR confirmed the preservation of functional groups and crosslinking efficiency in polysaccharide–protein hydrogels [5,6,57,58].

In summary, FTIR analysis validated that hydrogels derived from NaCMC from pineapple stubble have the same functional integration as those obtained from commercial NaCMC, supporting their potential use in biomedical and pharmaceutical applications.

3.2.2. Scanning Electron Microscopy (SEM)

The microstructural analysis of the hydrogels obtained from NaCMC-Co and NaCMC-Pi is presented in Figure 3. Both materials exhibit a markedly porous morphology, which is fundamental for water retention and mass transport in biomedical use. The hydrogel prepared with commercial NaCMC (NaCMC-Co; Figure 3a) has a more homogeneous pore network, whereas the hydrogel synthesized with NaCMC from pineapple stubble (NaCMC-Pi; Figure 3b) has a broader pore size distribution and slightly more heterogeneous architecture. The broader pore size distribution observed in NaCMC-Pi hydrogels may be related to residual hemicellulose and natural variability in biomass-derived cellulose, which can influence crosslinking density and morphology [9,23,24]. These differences indicate that the NaCMC source can influence the pore structure, with potential implications for mechanical stability, swelling behavior, and biodegradability.

These porous morphologies are consistent with reports on cellulose-based hydrogels, where interconnected pores underpin fluid uptake and diffusion [1,3,7]. In wound care and tissue engineering, these features support oxygen/nutrient transport and cell infiltration [5,6,10,15]. Comparable porous networks in citric acid–crosslinked NaCMC systems have been associated with enhanced swelling and sustained drug release [57,58], supporting the suitability of both NaCMC-Co and NaCMC-Pi hydrogels for controlled-release platforms and wound dressings.

3.2.3. Differential Scanning Calorimetry and Thermogravimetric Analysis

Thermogravimetric (TGA) and differential scanning calorimetry (DSC) analyses (Figure 4a,b) revealed the typical three-stage degradation patterns of the NaCMC-based hydrogels (water loss at 50–150 °C, polymer decomposition at 200–400 °C, and carbonization above 400 °C) [3,7,33]. NaCMC-Pi/Gel exhibited a slightly higher degradation temperature (360 °C vs. 350 °C for NaCMC-Co/Gel) and greater residual mass, suggesting enhanced thermal stability and inorganic retention from lignocellulosic biomass [12]. DSC confirmed these trends, with NaCMC-Pi/Gel showing a more gradual thermal transition, consistent with a more stable crosslinked network. These findings align with recent studies demonstrating that cellulose origin and substitution degree modulate the stability of CMC hydrogels, reinforcing their potential in biomedical and controlled-release applications [7,23,37]. These characteristics are particularly relevant for biomedical and controlled-release applications, where thermal and structural stability are critical [5,6,10,11,15].

3.2.4. Swelling Degree and Gel Fraction Analysis

The gel fraction after 24 h was 23% for the NaCMC-Co hydrogels, with a maximum swelling degree of 2903% over six days, whereas the NaCMC-Pi hydrogels reached a 25% gel fraction and 656% swelling. As shown in Figure 4c,d, equilibrium was achieved rapidly within the first 5 h, while the extended kinetics confirmed structural stability over six days, underscoring the potential of these hydrogels for pharmaceutical and biomedical applications.

The greater swelling of NaCMC-Co compared to that of NaCMC-Pi is likely linked to the lower crosslinking density and chain substitution patterns, which is consistent with reports that a reduced gel fraction enhances water uptake at the cost of network strength [3,7]. This behavior aligns with that of superabsorbent hydrogels designed for wound care or exudate management [6,33]. In contrast, the moderate swelling but relatively high stability of NaCMC-Pi could be advantageous for controlled release and scaffold applications, where dimensional integrity is essential [5,9]. Overall, the contrasting swelling–gel fraction profiles highlight the tunability of NaCMC-based hydrogels and their suitability for distinct biomedical contexts.

In addition, the porous morphology described in Section 3.2.2 (SEM) reinforces the potential of these hydrogels for sustained drug release, since interconnected pores facilitate diffusion pathways. Although drug release experiments were not conducted in this phase, future studies will incorporate angiogenic and tissue-regenerative molecules as model drugs. Curcumin (Curcuma longa), a compound with well-documented angiogenic properties, is proposed as a representative candidate, while the system can be adapted to other bioactive agents relevant for wound healing and tissue regeneration [16].

3.3. Energy and Environmental Efficiency of the Process

The average yield of dry crude fiber obtained from pineapple stubble was 17.2%, while the yield of purified cellulose relative to the treated fiber reached 19.5%, equivalent to 19.5 g of cellulose per 100 g of crude fiber. These values, calculated according to Equation (4), indicate an efficient conversion of lignocellulosic biomass into high-purity cellulose suitable for pharmaceutical applications, consistent with atom economy and sustainable process design principles [19,38,40].

The synthesis of NaCMC using 5 g of purified cellulose produced 6.5 g of dry polymer, corresponding to a 130% yield relative to the initial mass, which reflects the incorporation of carboxymethyl groups during etherification. The degree of substitution (DS = 0.77) was within the optimal range reported for pharmaceutical-grade NaCMC (0.65–0.85) [59,60], confirming that pineapple biomass can be efficiently converted into a functional cellulose derivative.

From an operational standpoint, the total energy consumption of the process—from milling to final drying—was estimated at 39.37 kWh per batch. Although this value corresponds to laboratory-scale conditions, it falls within the moderate energy demand reported for cellulose modification (0.3–10 kWh·g⁻¹) [19,44,45]. Scaling up would proportionally reduce the specific energy consumption, and further optimization could be achieved through thermal recovery and solvent reuse strategies [44,47].

The experimental E-factor, calculated according to Equation (5) as the ratio of non-recoverable waste to dry NaCMC obtained, was 107.1 at laboratory scale. This high value is typical of laboratory processes where solvent recovery is not implemented and has now been explicitly framed as such. Assuming 85% recovery of alcohols via rotary evaporation [46,47] the projected E-factor decreases to approximately 15. This estimate aligns with reported ranges (10–30) for other biopolymer syntheses, supporting the feasibility of achieving a substantially lower value under scaled-up conditions [21,61].

Overall, these findings confirm that the NaCMC synthesis pathway is technically efficient and environmentally consistent with the principles of green chemistry. The integration of solvent recovery and the valorization of pineapple biomass as a renewable feedstock reinforce the sustainability potential of the process and position it as a competitive alternative for pharmaceutical materials

4. Conclusions

Sodium carboxymethylcellulose (NaCMC) synthesized from pineapple stubble demonstrated physicochemical properties fully compliant with pharmacopoeial standards and proved suitable for hydrogel formulation. The resulting NaCMC–gelatin hydrogels crosslinked with citric acid exhibited structural equivalence to those prepared with commercial NaCMC, with comparable swelling behavior and slightly enhanced thermal stability. These findings confirm that biomass-derived NaCMC can serve as a reliable pharmaceutical excipient for controlled drug release and wound-healing applications. In addition, the use of agro-industrial residues provides an added sustainability benefit, supporting cleaner production practices without compromising the pharmaceutical performance of the material. Importantly, the environmental assessment highlighted moderate energy demand and an experimental E-factor of 107.1 under laboratory conditions, a value typical of lab-scale processes. With solvent recovery strategies, this factor is projected to decrease to ~15, aligning with reported ranges for biopolymer syntheses, thereby reinforcing the feasibility and sustainability potential of the process.