Hypertension is identified as a cardiovascular risk factor, and is often called a ‘‘silent killer’’ because hypertensive individuals are often asymptomatic for years. Hypertension is a worldwide problem of epidemic proportions that affects 15–20% of all adults. Due to the potential antioxidant and antihypertensive properties of FSGH2 and FSGH4, further research is needed to explore their possible use as natural supplementary raw materials in food and nutraceutical products. Taken together, FSGH2 and FSGH4 showed high antioxidant activity and potent anti-ACE activity. In addition, FSGH2 and FSGH4 showed higher angiotensin-I-converting enzyme (ACE)-inhibitory activity as compared to FSGH1 and FSGH3. Additional biological functional analyses showed that all of the studied gelatin hydrolysates FSGH1–FSGH4 possessed antioxidant activity dose-dependently as revealed by DPPH scavenging, ABTS scavenging, and reducing power analyses. Moreover, the physicochemical characteristics of FSGH1–FSGH4 were examined by analyses of their degree of hydrolysis, amino acid composition, UV spectrum, FTIR spectrum, molecular weight, and RP-HPLC profile. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform infrared (FTIR) analyses showed the extracts FSG1 and FSG2 possessed characteristics of gelatin. The extrusion-pretreatment process enhanced the extraction yield of gelatin from fish scale. In the current study, fish gelatin was extracted from non-extruded milkfish scale (FSG1) or extrusion-pretreated milkfish scale (FSG2) extracted gelatins were hydrolyzed with different combinations of Flavourzyme and Alcalase to give four different hydrolysates, namely: FSGH1 (FSG1 hydrolyzed with Flavourzyme), FSGH2 (FSG1 hydrolyzed with Alcalase + Flavourzyme), FSGH3 (FSG2 hydrolyzed with Flavourzyme), and FSGH4 (FSG2 hydrolyzed with Alcalase + Flavourzyme). Numerous approaches were developed to ameliorate the lyophilization performance.Fish gelatin hydrolysates have been shown to possess various biological activities due to their unique Gly-Pro-Y and Gly-X-Hyp sequences.The formulation excipients and the dispersion medium play crucial roles in designing a successful process.Optimizing the lyophilization cycle requires controlling the process parameters.Lyophilization is a propitious drying technique for thermolabile materials.In addition, this work points out the quality by design (QbD), critical quality of attributes (CQAs), limitations, and drawbacks of lyophilization. This review attains to disassemble freeze-drying complications through a detailed explanation of the lyophilization concept, stages, the factors influencing the process including controlled ice nucleation, and the modified and innovative freeze-drying technologies proposed in recent years to overcome the shortage of traditional freeze-drying. Although FD possesses several merits as its suitability for thermolabile materials and its ability to produce dry products with high-quality attributes, it is a complex and prolonged process that requires optimization of both process and formulation variables. It is a drying process where the solvent is crystallized at low temperatures and then sublimed from the solid-state directly into the vapor phase. Freeze-drying (FD) is the most substantial drying technique utilized in the pharmaceutical and biopharmaceutical industries.
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