Comparative synthesis of acid-hydrolyzed nanocrystalline starch preparation methods.
| Comparison | Evidence from reviewed studies | Interpretation |
|---|---|---|
| Highest reported crystallinity | HCl hydrolyzed Dioscorea starch showed relative crystallinity up to 71.3%; ethanol-acid penetration with dry heating showed crystallinity of 61.22%; supercritical CO2 pretreatment followed by enzymatic hydrolysis showed crystallinity of 60.2%. | HCl hydrolysis can produce high crystallinity, but newer assisted methods may also improve crystallinity while reducing processing time. |
| Highest reported yield | Dry-heated oxalic acid hydrolysis showed the highest reported yield of 89.6%, followed by H2SO4 hydrolysis of cassava starch with yield of 85.66%. | High yield does not necessarily indicate better nanocrystalline quality because higher yield may occur with lower crystallinity. Yield and crystallinity should therefore be interpreted together. |
| Shortest preparation time | Ultrasound assisted H2SO4 hydrolysis produced particles within 45 min, while mixed HCl/H2SO4 hydrolysis reduced preparation time to 1 h. | Assisted hydrolysis methods are promising for time reduction, but their reproducibility, crystallinity retention, and suitability for pharmaceutical processing require further confirmation. |
| Operational simplicity | Conventional HCl or H2SO4 hydrolysis. | These methods are widely reported and technically simple, but they often require long hydrolysis times and may produce low yield. |
| Potential scalability | Heat moisture pretreatment followed by H2SO4 hydrolysis, mixed acid hydrolysis, and organic acid-based hydrolysis. | These approaches may offer better balance between processing time, operational simplicity, yield, and product quality, but scale-up evidence remains limited. |
| Potential pharmaceutical suitability | Methods that produce reproducible crystallinity, minimize harsh processing concerns, and generate material suitable for drying, agglomeration, or direct-compression evaluation. | Pharmaceutical suitability cannot be judged by crystallinity alone; residual acid control, batch reproducibility, flowability, compactibility, and excipient safety also need consideration. |
| Direct-compression relevance | Spray dried or agglomerated acid hydrolyzed starch excipients reporting flow indices, compression force/pressure, tensile strength or hardness, friability, disintegration, dilution capacity, and lubricant sensitivity. | Direct compression relevance is strongest when studies evaluate tablet performance, not only particle preparation. |