Data screening and selection of studies

We searched Scopus, MEDLINE, Embase^®, and PubMed using keywords related to SNCs, acid-modified starch, hydrolyzed starch, acid hydrolyzed starch, nanostarch, nano starch, microcrystalline starch, and starch as a direct compression filler. Filters were applied to identify studies published between 2000 and 2025. A supplementary snowball search was conducted by screening the reference lists of eligible full text articles and by using Google Scholar and Scopus to identify articles that cited them. The database search was updated on August 6, 2024, followed by additional snowball and supplementary searches on November 10, 2025, using the same strategy and restricted to studies published from 2000 onward. Review articles, book chapters, conference abstracts, studies related to environmental or petroleum applications, and studies reporting lower crystallinity products, particularly those prepared by enzymatic hydrolysis, were excluded because such materials are better described as starch nanoparticles rather than SNC. Studies lacking appropriate characterization techniques, especially X-ray diffraction, to distinguish SNC from starch nanoparticles were also excluded. Studies on starch nanoparticles were included only when they exhibited higher crystallinity than native starch, and all studies on SNC reporting pharmaceutical applications in tablet formulations were included. Only articles published in English were included. The review protocol was not registered. Study screening was performed using predefined eligibility criteria. Titles and abstracts were first screened for relevance, followed by full text assessment of potentially eligible studies. Disagreements or uncertain eligibility decisions were resolved through discussion among the authors. Data were charted using a predefined extraction framework including starch source, preparation method, acid type, hydrolysis time, particle size, crystallinity, yield, drying method, flow behavior, compression conditions, tablet hardness or tensile strength, friability, disintegration, dilution capacity, and lubricant sensitivity where available. A formal risk of bias assessment was not conducted because the objective of this review was to map the available evidence, terminology, preparation methods, and excipient performance gaps rather than to estimate pooled treatment effects. The general search terms and Boolean operators were adapted for each database, as summarized in Table 2. The inclusion and exclusion criteria are summarized in Table 3. The excluded articles and reasons for exclusion are presented in Table 4, and the flow chart of the systematic review is shown in Figure 2.

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Figure 2. PRISMA-style flow diagram of study selection for the systematic review. This flow diagram was drawn in accordance with PRISMA guidelines (adapted from https://www.prisma-statement.org/prisma-2020-flow-diagram). © 2024–2026 the PRISMA Executive. Licensed under a CC BY 4.0.

Data collection and interpretation

The characteristics of SNC obtained from various plant sources were reviewed in terms of crystallinity, particle size, drying method, flow behavior, and compression conditions relevant to their use as direct compression fillers in tableting.

SNC preparation techniques

Research on SNC began in the late nineteenth century; however, limited progress was made until the twentieth century. In 2001, Atichokudom-chai et al. [35] prepared tapioca SNC by hydrolyzing a tapioca starch suspension in 6% w/v HCl at room temperature for up to 32 days to explore the use of SNC as direct compression excipients. The resulting SNC showed a relative crystallinity of 57.75%. Two years later, Putaux et al. [36] first reported that six weeks of acid hydrolysis with 2.2 N HCl at room temperature produced platelet like structures measuring 20–40 nm in length, 15–30 nm in width, and 5–7 nm in thickness. Angellier et al. [37] later modified the method by replacing HCl with H₂SO₄ and prepared waxy maize SNC using 3.16 mol/L H₂SO₄ at 40°C and 100 rpm for 5 days. Under these conditions, SNC with a 15.7% yield was obtained, with a morphology similar to that produced by HCl after six weeks of hydrolysis. This method has since been widely used as a standard approach for SNC preparation. The low yield of SNC has been attributed to the decline in native starch crystallinity and the need for prolonged acid treatment to obtain uniform SNC, during which preformed SNC may undergo partial hydrolysis [38]. In another study, SNC prepared from Dioscorea starch by HCl hydrolysis showed higher crystallinity and yield [39].

Several approaches have been proposed to shorten production time and increase the crystallinity of SNC. Enzyme pretreatment has been shown to reduce the time required for SNC synthesis. Among α-amylase, β-amylase, and glucoamylase, glucoamylase was the most effective for producing microporous starch. Pretreating waxy corn starch with glucoamylase for 2 h enabled the effects of traditional acid hydrolysis for 24 and 120 h to be achieved after only 6 and 45 h of acid hydrolysis, respectively [40]. More recently, researchers have explored ultrasonication combined with acid hydrolysis for SNC preparation. Amini and Razavi [41] reported that SNC could be produced within 45 min by simultaneously treating corn starch with ultrasound and H₂SO₄ hydrolysis. The resulting particles were smaller than 100 nm, with a yield of 21.6%. However, this approach has not been widely adopted because it often requires specialized equipment and may reduce SNC crystallinity by affecting the crystalline regions non selectively.

Saeng-On and Aht-Ong [42] investigated acid hydrolysis of banana and tapioca starch and compared the efficiency of HCl and H₂SO₄. Relative crystallinity values of 47.13% for banana starch and 60.06% for tapioca starch were obtained using H₂SO₄. These findings are consistent with previous studies on waxy maize starch: LeCorre et al. [30] used HCl, whereas Jiang et al. [31] used H₂SO₄ to prepare SNC. Wei et al. [32] reported that although H₂SO₄ produced lower SNC yields than HCl, the suspensions obtained with H₂SO₄ were more stable. Sulfate esters introduce negative charges on the SNC surface, increasing the zeta potential of the suspension. The resulting electrostatic repulsion reduces particle aggregation and produces a more stable and homogeneous suspension than hydrochloric acid-hydrolyzed SNC, which lacks sulfate groups [32]. Ball milling has also been used as a pretreatment to reduce the preparation time of SNC from 5 days to 2 days. After ball milling and hydrolysis of waxy corn starch with 3.12 mol/L H₂SO₄, SNC measuring 20–40 nm, with a yield of 19.3% and crystallinity of 47.7%, were obtained [43]. However, the use of ethanol as a wet ball milling agent raises environmental concerns. Hao et al. [44] used glucoamylase to pretreat waxy potato starch and obtained square shaped SNC with diameters of 50–100 nm and excellent dispersibility after 5 days of hydrolysis. However, enzyme pretreatment introduces additional substances that complicate subsequent isolation and purification. Enzymatic hydrolysis alone also tends to produce nanostarch rather than SNC, with lower crystallinity [45]. Dai et al. [46] combined heat moisture pretreatment with H₂SO₄ hydrolysis and effectively produced SNC within 4 days, achieving a yield of 26.7% and relative crystallinity of approximately 50%. This approach offers good efficiency and operational simplicity, making it a promising option for SNC preparation. Further innovation in pretreatment technologies, such as irradiation, ultra-high pressure, electrophoresis, and magnetophoresis, may further improve SNC preparation efficiency and facilitate large scale production. Organic acids have also received recent attention because they are easier to recover, less corrosive, and may introduce useful functional group changes. Zhou et al. [1] reported a yield of 89.6% and crystallinity of 38.5% for waxy maize SNC prepared by dry heated oxalic acid treatment; however, yield decreased as crystallinity increased because of hydrolysis of the starch crystalline regions. Nlandu et al. [47] reported a method involving supercritical CO₂ pretreatment followed by enzymatic hydrolysis using pullulanase, which produced SNC with sizes of 20–150 nm and crystallinity of 60.2%. More recently, a neutral dispersion and acidic precipitation method was used to prevent excessive hydrolysis during SNC preparation from waxy potato starch by H₂SO₄ hydrolysis. This approach removed larger particles at pH 7 and precipitated highly crystalline, stable SNC at pH 5, thereby improving yield and quality while producing smaller particles with better thermal stability [48]. Li et al. [49] reported an SNC preparation method using a mixture of HCl and H₂SO₄ that substantially reduced preparation time (1 h versus 5 days) and produced higher relative crystallinity than conventional H₂SO₄ hydrolysis. The study also showed that the mixed acid method could convert A-type starch into V-type crystalline starch. Hu et al. [50] recently reported an ethanol acid penetration and dry heating method for SNC preparation. Using a mixture of 40% ethanol and 10.6 mM chloric acid and heating for 1.5 h, SNC were formed within 48 h rather than the 5 days required for conventional acid hydrolysis. The resulting SNC were smaller, showed lower yield but higher crystallinity, and possessed superior thermal stability. In summary, current SNC preparation methods mainly focus on particle size, yield, crystallinity, and hydrolysis time. The different methods used to prepare acid-hydrolyzed nanocrystalline starch are summarized in Table 5. A comparative synthesis of preparation methods is presented in Table 6. The reviewed preparation methods show clear trade-offs among crystallinity, yield, hydrolysis time, and pharmaceutical processability. Conventional HCl and H₂SO₄ hydrolysis remain the most widely reported and technically simple approaches, but they often require prolonged processing time and may provide limited yield. Assisted approaches, including ultrasonication, mixed acid hydrolysis, heat moisture pretreatment, supercritical CO₂ pretreatment, organic acid hydrolysis, and ethanol acid dry heating, may shorten preparation time or improve selected material attributes. However, their reproducibility, scalability, residual processing concerns, and pharmaceutical suitability require further confirmation. The highest reported yield was not necessarily associated with the highest crystallinity, indicating that yield alone is insufficient for judging nanocrystalline starch quality. For direct compression applications, the most relevant evidence comes from studies that connect material attributes with flow behavior, compactibility, tablet hardness or tensile strength, friability, disintegration, dilution capacity, and lubricant sensitivity. Therefore, future work should integrate preparation method, material characterization, powder engineering, and tablet performance testing rather than reporting particle preparation alone.

Acid-modified nanocrystalline starch as a direct compression tablet excipient

Pharmaceutical products play a crucial role in the global effort to diagnose and treat disease and to improve overall well-being at lower cost. Among solid dosage forms, tablets are particularly preferred because they are easy to administer, cost effective, convenient, and have a long shelf life. Tablets are commonly produced by compacting a blend of drug powder and excipients into a solid mass. Direct compression is favored because of its simplicity, cost effectiveness, and time efficiency [54]. With the advent of high-speed tableting equipment and greater reliance on direct compression, the performance requirements for excipients continue to increase. Tablet quality is strongly influenced by the diluents or fillers used, which should have suitable particle size, deformability, and stability. Native starch, however, lacks the flowability and compressibility needed for use as a direct compression filler [55]. It therefore needs to be modified, and acid treatment is among the most cost-effective modification methods. Acid-modified starches have shown improved flowability and compressibility, making them more suitable for direct compression. The following section provides an overview of acid-modified nanocrystalline starch and related starch-based excipients evaluated as direct-compression tablet excipients from 2003 onward. For direct-compression applications, acid-hydrolyzed nanocrystalline starch may be used either as a fine crystalline material or converted into larger engineered particles through spray drying or agglomeration. Therefore, studies involving spray-dried or agglomerated starch-based excipients are discussed separately where the reported improvement in flow or tableting performance may arise partly from particle size enlargement, morphology modification, or co-processing rather than from nanocrystallinity alone. Flowability is a critical material attribute for direct compression excipients and cannot be predicted from crystallinity alone. Although acid hydrolysis may improve crystallinity and compactibility, nanoscale or very fine particles generally show stronger cohesive forces, including van der Waals attraction, electrostatic interaction, and moisture related adhesion. These interactions may reduce powder flow and cause poor die filling during tableting. Therefore, the direct compression performance of acid-modified nanocrystalline starch should be evaluated using multiple powder and tablet attributes, including particle size distribution, morphology, true density, bulk and tapped density, Carr’s index, Hausner ratio, angle of repose, moisture content, electrostatic tendency, agglomerate strength, lubricant sensitivity, compactibility, tabletability, and dilution potential. Spray drying, agglomeration, or co-processing may improve flow by increasing particle size, producing more spherical particles, reducing interparticle cohesion, and improving packing behavior. Compression performance should also be interpreted mechanistically rather than only by reporting hardness or friability values. Acid modification and nanocrystalline domain enrichment may improve compactibility by increasing surface roughness, exposing additional bonding sites, and promoting interparticulate bonding during compression. Depending on the starch source and processing method, compaction may involve a combination of plastic deformation, brittle fragmentation, particle rearrangement, and moisture mediated bonding. Higher crystallinity may contribute to stronger compact formation, but excessive fine particle cohesion may reduce flow and die filling. Lubricant sensitivity is also important because hydrophobic lubricants can reduce bonding between starch particles and lower tablet strength. Therefore, tabletability should be interpreted using tensile strength, friability, disintegration, dilution capacity, and lubricant sensitivity in addition to simple crushing strength or hardness. This is particularly important for formulations containing poorly compressible model drugs such as paracetamol, where the excipient must maintain tablet strength at higher drug loading.

To investigate the potential of rice starch as a direct compression filler, both nonwaxy and waxy rice starches were subjected to partial hydrolysis in 6% w/v HCl at ambient temperature for different durations. This process increased crystallinity and produced acid-modified rice starches. Scanning electron micrographs showed that after 192 h of hydrolysis, acid-modified waxy rice starch exhibited surface exo-corrosion, whereas acid-modified rice starch remained unaltered. Hydrolysis reduced amylose content and particle size, and X-ray diffraction confirmed that relative crystallinity increased with longer hydrolysis times. Spherical agglomerates of native and acid-modified starches were compressed into tablets using a single punch rotary tablet machine, and higher crystallinity improved crushing strength and disintegration time while reducing friability [56]. Atichokudom-chai et al. [35] prepared cross-linked tapioca starch and then hydrolyzed it with 6% w/v HCl for 192 h. The final product was spray dried to obtain agglomerated acid-modified cross-linked tapioca starch. Cross linking did not increase the relative crystallinity or melting enthalpy of tapioca starch. Upon compression, both native and cross-linked tapioca starches showed low crushing strength. Acid hydrolysis removed noncrystalline regions and increased crystallinity, resulting in higher tablet hardness. In this study, tablets prepared from acid-modified cross-linked tapioca starch showed better performance than those prepared from acid-modified tapioca starches (ACMS). Furthermore, Akin-Ajani et al. [57] investigated the compressional behavior of acid-modified white fonio and sweet potato starches. They reported significant differences in the physicochemical and compressional properties of the two starches. Acid modification increased solubility and crystallinity while decreasing swelling and viscosity. Modified starches showed earlier onset but lower overall plastic deformation under pressure and produced stronger tablets at lower compression pressures than native starches. Longer steeping times increased tablet tensile strength, suggesting that modified fonio and sweet potato starches have potential for direct compression formulations. However, despite improvement over native starch, flow remained poor after acid modification, indicating the need for further enhancement of powder flow properties. Particle size enlargement is one strategy to improve flow. Smaller particles have a higher surface to volume ratio, which increases cohesive forces such as van der Waals and electrostatic interactions. These stronger forces hinder particle rearrangement and packing, resulting in more interstitial voids, lower bulk density, and a higher Hausner ratio, all of which indicate poorer flowability.

Odeku and Picker-Freyer [26] prepared acid-modified starches from four Dioscorea species: White yam (D. rotundata), Water yam (D. alata), Chinese yam (D. oppositifolia), and Bitter yam (D. dumetorum). Acid hydrolysis increased solubility and reduced swelling, while also improving compressibility relative to the native starches. Intact and stable tablets were obtained only at higher maximum relative densities for acid-modified water yam and white yam. By contrast, tablets prepared from acid-modified Chinese yam and bitter yam showed deformation at all relative densities. Nevertheless, the tablets exhibited higher crushing strength and acceptable disintegration times, indicating potential utility as excipients for direct compression.

Tessema et al. [58] evaluated the effects of acid modification and drying method on Dioscorea starch. The starch was hydrolyzed in 6% HCl for 8 days and then dried by either oven drying or spray drying. Native Dioscorea starch and oven-dried acid-modified Dioscorea starch showed unsatisfactory flow properties, whereas the spray-dried acid-modified starch exhibited improved flow, with a flow rate of 13.24 g/s and an angle of repose of 21.37°. The swelling power and percentage solubility of the starches increased with temperature. The acid-modified starch showed a solubility of 68.53%. Tablets were prepared using a single punch press under a constant compression force. The spray dried acid-modified starch was less sensitive to lubricant than the oven dried sample and Starch 1500^®. It also showed a crushing strength of 50.9 N. Gulla et al. [59] prepared and characterized acid-modified Ethiopian potato starch as a directly compressible excipient and compared it with native Ethiopian potato starch and Starch 1500^®. The starch was hydrolyzed with 6% HCl for 8 days and then dried by oven drying or spray drying. Acid hydrolysis reduced moisture content and swelling power while increasing solubility. Spray dried acid-modified Ethiopian potato starch showed better flowability than the native starch. Tablets containing paracetamol and a lubricant were prepared using a single punch tablet machine at a compression force of 15 kN. Compactability testing showed that the tensile strength of spray dried acid-modified Ethiopian potato starch was substantially higher (16.76 kg/cm²) than that of spray dried native Ethiopian potato starch (7.07 kg/cm²) and Starch 1500^® (11.66 kg/cm²). The modified starch showed lower lubricant sensitivity and higher dilution potential than the native starch and Starch 1500^®. It accommodated up to 50% paracetamol, whereas the native starch and Starch 1500^® could accommodate only 30% (Gulla et al. [59]).

To study tabletability, ACMS and alkali-modified tapioca starches (ALMS) were prepared using HCl or NaOH solutions at concentrations of 0.1–1.0 N for 48 h, followed by tray drying and sieving through a 150 μm sieve. The particle size ranged from 75 to 150 μm. Both ACMS and ALMS showed poor flow characteristics. Propranolol tablets were prepared using native starch, ACMS, and ALMS at a compression pressure of 12.3 MPa. ACMS tablets showed higher hardness (38.02 N) than ALMS tablets (8.04 N), likely because the rougher surface of ACMS granules promoted cold welding at interparticulate contact points. The disintegration time and dissolution rate of ACMS tablets were comparable to those of ALMS tablets in both acidic and neutral media. The results also showed that ACMS prepared with higher HCl concentration (1 N) and ALMS prepared with higher NaOH concentration (0.2 N) exhibited greater crystallinity than native starch, whereas particle size decreased as acid or base concentration increased [60]. These findings are consistent with previous reports showing that stronger acid or alkaline treatment can reduce starch particle size; Md Shahrodin et al. [53] also reported that higher acid concentration reduced particle size in SNC prepared using HCl and H₂SO₄.

More recently, researchers prepared acid-modified Taro Boloso-I starch (AMTBIS) by hydrolyzing it in 6% w/v HCl for 192 h followed by spray drying. The resulting product was evaluated for compactibility in direct compression. The acid-treated starch showed reduced moisture content, increased crystallinity, and improved flow properties. Compaction studies also demonstrated better compactibility, with a tensile strength of 16.82 kg/cm², which was higher than that of the native starch (13.17 kg/cm²) and Starch 1500^® (11.2 kg/cm²). In addition, paracetamol tablets prepared with spray-dried AMTBIS using a single-punch tablet machine showed greater hardness (53.5 N) than tablets prepared with native Taro Boloso-I starch (38.5 N) and Starch 1500^® (37.8 N), together with lower friability at all paracetamol concentrations. The formulation accommodated up to 40% paracetamol while maintaining satisfactory tablet properties, whereas native starch and Starch 1500^® were limited to 30% (w/w) [61].

In another study, Siriwachirachai and Pongjanyakul [62] prepared ACMS agglomerates using polyvinylpyrrolidone (PVP) as an agglomerating agent to improve flow properties and particle strength, with particle sizes ranging from 75 to 150 μm. The ACMS agglomerates showed good flowability. Tablets were prepared using a hydraulic press at compression pressures of 4.9–12.3 MPa. ACMS agglomerate tablets containing 4% PVP showed greater particle strength than native starch agglomerates. The findings demonstrated that increasing the acid concentration to 1 N during ACMS modification increased crystallinity, which in turn improved compressibility and tablet hardness compared with native starch. Incorporation of PVP prolonged disintegration time and reduced the dissolution rate in both acidic and neutral media. ACMS agglomerated tablets also showed good carrying capacity for acetaminophen up to 30%, with desirable characteristics for direct compression using a single-punch tablet machine [62]. The properties and performance of acid-hydrolyzed SNCs and related acid-modified starch excipients used as direct compression fillers are summarized in Table 7.

Challenges and perspectives

Although acid-modified nanocrystalline starch shows promise as a direct compression tablet excipient, several technical, pharmaceutical, regulatory, and manufacturing challenges remain before broader industrial adoption. These challenges are not limited to crystallinity or tablet hardness, but also include process scalability, purification, batch reproducibility, powder flow, excipient safety, regulatory acceptance, and commercial feasibility.

Manufacturing scalability and acid recovery

Conventional acid hydrolysis remains one of the most widely used methods for preparing acid-modified nanocrystalline starch; however, long hydrolysis time, low or variable yield, high acid consumption, and repeated washing steps limit its industrial scalability. Large scale production would require better control of acid concentration, temperature, starch to acid ratio, reaction time, neutralization, and drying conditions. Acid recovery and reuse are also important because mineral acid hydrolysis may generate acidic waste streams and increase production cost. Newer approaches, including assisted hydrolysis, organic acid treatment, heat moisture pretreatment, and combined physical-chemical methods, may reduce preparation time, but their scalability and batch reproducibility still require systematic evaluation.

Residual acid, sulfate esterification, and excipient safety

For pharmaceutical use, residual acid and by-products from the hydrolysis process must be carefully controlled. Sulfuric acid hydrolysis may introduce sulfate ester groups on the starch surface, which can improve dispersion stability but may also alter excipient behavior, compatibility, and safety profile. Hydrochloric acid and organic-acid methods may avoid some sulfate related changes, but they still require adequate purification, neutralization, and drying. Future studies should therefore report residual acid, pH, ash content, ionic residues, surface substitution where relevant, and compatibility with model drugs and common excipients. Safety evaluation should also include cytotoxicity, irritation potential, microbial quality, and stability under storage conditions.

Batch to batch variability from botanical source

Starch properties depend strongly on botanical source, amylose to amylopectin ratio, granule morphology, native crystallinity, lipid and protein content, and harvesting or processing conditions. As a result, acid-modified nanocrystalline starch prepared from different sources may show different particle size, crystallinity, yield, flow behavior, and compaction performance. Even within the same botanical source, batch to batch variability may occur if raw material quality and hydrolysis conditions are not tightly controlled. Standardized specifications for starting starch, hydrolysis conditions, crystallinity, particle size distribution, moisture content, and powder performance are therefore necessary for reproducible excipient development.

Powder flow engineering and co-processing

One major limitation of nanocrystalline or very fine starch particles is poor flowability. Although acid hydrolysis may improve crystallinity and compactibility, small particle size can increase interparticle cohesion, electrostatic effects, and moisture related adhesion. These properties may impair die filling and weight uniformity during direct compression. For this reason, spray drying, agglomeration, granulation, or co-processing with binders and flow enhancing excipients may be required. However, when improved flow or tabletability is observed after agglomeration or spray drying, the improvement should not be attributed to nanocrystallinity alone. Future studies should distinguish the contribution of crystallinity from the contribution of particle engineering.

Regulatory pathway for novel starch-based excipients

Although starch and several modified starches are already used in pharmaceutical formulations, acid-modified nanocrystalline starch intended as a direct compression excipient may require additional regulatory justification, especially if the material differs substantially in particle size, surface chemistry, crystallinity, or manufacturing process from established starch excipients. Regulatory acceptance would require clear specifications, validated manufacturing controls, impurity limits, safety data, stability data, and compatibility information. The regulatory pathway may be easier if the material is developed as a co-processed starch-based excipient with well-defined quality attributes and consistent performance.

Quality by design framework for starch-based excipients

A quality by design approach would be useful for future development of acid-modified nanocrystalline starch excipients. Critical material attributes may include botanical source, amylose content, particle size distribution, morphology, crystallinity, moisture content, density, Carr’s index, Hausner ratio, angle of repose, compactibility, lubricant sensitivity, and dilution potential. Critical process parameters may include acid type and concentration, hydrolysis time, temperature, agitation, starch concentration, washing, neutralization, drying method, and agglomeration conditions. Linking these process parameters and material attributes to tablet performance would help establish a rational design space for direct-compression applications.

Commercial gaps

At present, there is limited commercial standardization for acid-modified nanocrystalline starch as a direct compression excipient. Many studies report crystallinity, particle size, hardness, or friability, but fewer studies provide complete excipient specifications or compare performance against established commercial fillers such as microcrystalline cellulose, lactose, dicalcium phosphate, or pregelatinized starch. Future studies should include benchmark comparisons with commercial excipients and report standard tableting outcomes such as flow indices, compression force, tensile strength, friability, disintegration, dissolution behavior, dilution capacity, and lubricant sensitivity.

Environmental and cost considerations

The environmental and economic feasibility of acid-modified nanocrystalline starch will depend on raw material availability, processing time, acid consumption, water use, washing requirements, drying energy, solvent recovery, and product yield. Although starch is renewable, biodegradable, and widely available, the environmental advantage may be reduced if preparation requires prolonged acid hydrolysis, large volumes of washing water, or energy-intensive drying. More sustainable preparation routes, including recoverable organic acids, reduced acid concentration, shorter reaction time, and efficient drying or agglomeration methods, should be investigated.

Future studies required before industrial adoption

Future research should move beyond particle preparation and provide integrated excipient performance evaluation. Studies should report standardized crystallinity, particle size distribution, morphology, flow indices, compactibility, tabletability, dilution capacity, lubricant sensitivity, drug excipient compatibility, stability, and safety data. Direct compression studies should include model drugs with different compressibility profiles and should compare acid-modified nanocrystalline starch with established commercial excipients under similar compression conditions. Scale-up studies, process validation, storage stability, and regulatory oriented safety assessment will be essential before acid-modified nanocrystalline starch can be considered for routine industrial use as a direct-compression tablet excipient.