As a new type of foreign trade service provider driven by technological transformation and foreign trade business, HiSiaddi has established a "1+2+3+4=1" service system and can supply chitosan sourced from multiple well-known original manufacturers.
Possessing R&D capabilities, HiSiaddi has repeatedly collaborated with factories on technological transformation and accurately captured market demands to propose chitosan formulation optimization schemes and application improvement suggestions. Below is a consultation case of chitosan product formulation optimization delivered by HiSiaddi.
Please contact HiSiaddi customer service if you require more formulation optimization consultation services.
The buyer is Bioformula Srl, a mid-to-high-end biopharmaceutical enterprise based in Milan, Italy, specializing in three premium product lines: medical wound repair dressings, gastrointestinal sustained-release capsules, and oral mucosal repair gels. Its products are sold in state-owned Italian pharmacy chains, private medical beauty institutions, and organic health supermarkets near the Swiss border. Raw materials comply with EP European Pharmacopoeia standards, Italy’s DM Food and Pharmaceutical Regulations, and LFGB control standards, with an annual total chitosan procurement volume of 11.2 tons, divided into three categories: low-molecular oral-grade, quaternary ammonium modified gel-grade, and high-molecular film-forming dressing-grade chitosan.
The enterprise previously sourced pharmaceutical-grade chitosan from French local manufacturers for a long time. Amid rising European raw material prices and factory capacity cuts, it initiated domestic Chinese raw material replacement. After purchasing raw materials from two domestic chitosan manufacturers for production on Italy’s GMP production lines, three major mass production failures emerged successively: abnormal capsule disintegration, gel stratification and water separation during storage, and easy cracking of dressing films.
Domestic manufacturers only produced off-the-shelf goods in compliance with national standards and solely controlled factory physical and chemical indicators, lacking familiarity with the customer’s terminal formulation systems and European production line operating conditions. They could not simultaneously implement rectification from both raw material and formulation perspectives. Production line shutdowns for debugging and finished product scrapping caused direct economic losses exceeding EUR 76,000, delaying the new product launch schedule by 60 days. The customer entrusted HiSiaddi’s technical team to comprehensively identify root causes and deliver technical rectification from three dimensions: raw material modification optimization, formulation ratio adjustment, and production process improvement.
The customer’s sustained-release capsules rely on slow swelling of chitosan in gastric juice to achieve long-term drug release, with internal control standards: disintegration rate ≤15% after 2 hours in artificial gastric juice, dissolution rate ≥85% after 6 hours. Conventional domestic low-molecular chitosan produced via traditional high-temperature alkaline hydrolysis features a broad molecular weight range of 10,000–50,000 Da with uneven molecular sizes. Small-molecule fractions dissolve rapidly in gastric acid, causing early drug burst release, while large-molecule fractions dissolve slowly and delay later-stage dissolution. Disintegration time errors of the same batch of capsules exceeded 3 hours, rendering large quantities of finished products non-compliant with Italian Pharmacopoeia release standards. Meanwhile, the raw material’s deacetylation degree fluctuated between 82% and 87%; low-deacetylation sites exhibited excessive hydrophilicity, further disrupting dissolution parameters.
The customer’s oral gel formulation blends modified chitosan with propylene glycol and plant extracts, requiring uniform gel without stratification after 12 months at room temperature. Domestic manufacturers adopted crude quaternary ammonium modification processes with quaternary ammonium substitution degrees ranging from 26% to 49%. Fractions with low substitution degrees lacked sufficient water solubility, failing to form a complete colloidal network within the system; fractions with high substitution degrees featured excessive hydrophilicity of molecules, and redundant free hydrophilic groups disrupted system balance, resulting in a clear water lower layer and thick paste upper layer after standing for 30–45 days, making the product unmarketable. In addition, trace residual protein impurities in raw materials triggered minor microbial growth during storage, causing slight yellowing and odor deterioration of the gel.
The customer’s sterile dressings rely on natural flow casting of chitosan to form films, with requirements that films withstand 180° bending without cracking while maintaining breathability and bacteriostasis. Domestic manufacturers adopted prolonged high-temperature deacetylation processes; high-temperature shearing fractured high-molecular chain segments, resulting in an actual molecular weight of only approximately 520,000 Da, far below the customer’s internal control index of 720,000–780,000 Da. High internal stress remained within formed films, leading to dense microcracks after drying, with a breakage rate of 32% during sterilization and packaging, drastically elevating production costs.
Domestic suppliers only monitored national standard indicators such as raw material purity and deacetylation degree, without supporting formulation application laboratories. They failed to understand the impacts of chitosan molecular weight and substitution degree on sustained release, gel formation, and film-forming performance, and could only passively produce off-the-shelf goods without targeted improvement of raw material properties or coordinated optimization of customer formulations.
HiSiaddi set up a special team consisting of chitosan raw material engineers, formulation pharmacists, and third-party testing specialists. Aligned with European Pharmacopoeia indicators, it coordinated domestic leading factories with enzymatic refining and refined modification qualifications to implement rectification in three phases: raw material process optimization, formulation system adjustment, and standardized on-site operation specifications.
1. Raw Material Process Rectification: Discontinue high-temperature strong alkaline hydrolysis and adopt directional biodegradation by chitosanase combined with nanofiltration membrane grading to precisely intercept narrow-range molecules of 23,000–28,000 Da, controlling the molecular weight dispersion coefficient within 9%. Low-temperature deacetylation procedures were optimized to stabilize the deacetylation degree at 90%±0.5%, eliminating dissolution deviations caused by fluctuating deacetylation degrees.
2. Formulation Fine-Tuning: HiSiaddi coordinated with the Italian R&D department to add 3% microcrystalline cellulose as a sustained-release regulator and adjust the proportion of lactose filler to buffer chitosan swelling rates. Small trial verification showed capsule disintegration of 13.2% after 2 hours in gastric juice and dissolution of 87.1% after 6 hours, fully meeting internal pharmacopoeia standards with batch dissolution errors controlled within ±3%.
1. Raw Material Modification Optimization: Factories controlled feed molar ratios, reaction temperatures, and pH values in sealed reaction kettles, adding quaternary ammonium reagents dropwise in stages to stabilize the quaternary ammonium substitution degree between 37% and 39%. Multi-stage ultrafiltration impurity removal procedures were added to eliminate residual free proteins and unreacted monomers, reducing the risk of colloidal demulsification induced by impurities.
2. Formulation System Optimization: The glycerol dosage in the formulation was slightly increased by 1.2%, paired with a 0.05% citric acid buffer system to stabilize gel pH and strengthen the colloidal network structure. Accelerated stability testing confirmed uniform, transparent gel without stratification, discoloration, or water separation after 120 days at room temperature.
1. Raw Material Production Optimization: Switch to fresh deep-sea Norwegian shrimp shell raw materials and adopt low-temperature staged alkaline deacetylation to avoid molecular chain cleavage at high temperatures, stabilizing the finished product molecular weight at 750,000 Da with a deacetylation degree of 90.2%. Spray drying parameters were optimized to reduce internal stress within powder.
2. Film-Forming Process Optimization: Guide the customer to increase the solid content of the liquid mixture, implement gradient low-temperature drying post flow casting to slowly release internal film stress, and blend a small amount of food-grade glycerol into the film-forming liquid to enhance flexibility. After improvement, dressing films withstand repeated bending without cracking, with the product breakage rate reduced from 32% to 1.8%.
Combined with production line parameters of the three product categories, HiSiaddi compiled bilingual production guidelines specifying chitosan feeding sequence, stirring speed, batching temperature, dissolution soaking duration, and standardized operating procedures for frontline operators to avoid finished product fluctuations caused by human error.
Four gradient batches of test samples passed full testing per EP Pharmacopoeia standards at an Italian third-party laboratory. A small trial purchase of 5.1 tons of optimized chitosan was put into production, with three production lines operating at full load for 72 consecutive hours without process failures and all finished products fully compliant. The customer finalized an annual framework procurement order of 11.2 tons: 4.3 tons for sustained-release capsules, 3.7 tons for oral gels, and 3.2 tons for dressings, shipped in 10 evenly distributed monthly batches. Leveraging domestically optimized raw materials, the customer completed Italian drug administration filing for the three new products on schedule and launched full-channel distribution.
1. Customer Benefits: Domestic raw material replacement reduced comprehensive procurement costs by 23.5%, recovering losses from early scrapping and production shutdowns. In the following year, the customer fully entrusted HiSiaddi with all chitosan procurement and technical services for its Spanish and Greek subsidiaries, expanding annual procurement volume to 15.7 tons.
2. Factory Benefits: Cooperating factories matured three standardized processes: narrow molecular weight grading, precise quaternary ammonium modification, and high-molecular chain preservation, forming a standardized product line for EU pharmaceutical-grade chitosan. They subsequently secured customized orders from two high-end pharmaceutical enterprises in Portugal and Slovenia.
3. Realized Service Value of HiSiaddi: Breaking the traditional model of pure product supply, HiSiaddi acts as a third-party technical service provider forming a two-way technical closed loop covering upstream raw material process improvement and downstream terminal formulation optimization, bridging information gaps between Chinese raw material applications and European customers.
Most domestic chitosan manufacturers prioritize mass production of general bulk goods in compliance with national standards with fixed production processes and lack formulation application research capabilities, only meeting basic food-grade demands. Formulations of mid-to-high-end European and American pharmaceutical enterprises are developed around imported European raw materials, leading to frequent physical and chemical mismatches and mass production failures after switching to domestic raw materials. Drawing on industrial chain resources and application technical reserves, HiSiaddi simultaneously implements rectification from both raw material source process transformation and terminal formulation optimization dimensions to efficiently resolve customer mass production challenges and help domestic high-end chitosan access Southern European pharmaceutical raw material supply chains.
Please contact HiSiaddi customer service if you require more formulation optimization consultation services.
+86-13120989737 
info@hisiaddi.com 
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