As a new-type foreign trade service provider driven by technological transformation and foreign trade services, HiSiaddi has established a "1+2+3+4=1" service system and can supply chondroitin sulfate sourced directly from multiple well-known original manufacturers.
Endowed with R&D capabilities, HiSiaddi has repeatedly proposed chondroitin sulfate formulation optimization solutions and application improvement recommendations through technological transformation cooperation with manufacturers and precise insight into market demands. Below is a formulation optimization consulting case completed by HiSiaddi for chondroitin sulfate products.
Should you require formulation optimization consulting services, please contact HiSiaddi customer service.
The cooperating party is ARTROCARE, a nutrition group headquartered in Barcelona, Spain. For over 30 years, it has focused on high-end medical joint preparations and sports nutrition raw materials for professional football leagues across the Iberian Peninsula and southern France. Its products are sold in rehabilitation departments of Spanish public hospitals, physical therapy supply chains for La Liga clubs, and local premium organic pharmacy chains. All products comply with the United States Pharmacopeia (USP), EU EFSA food raw material standards, Spanish AENOR food safety regulations, and TSE/BSE animal source control requirements. The group mainly produces three categories of high-end finished products: enteric-coated sustained-release tablets, composite softgels, and high-concentration joint oral liquids, with all raw materials used exclusively for proprietary formula medical food products – distinct from low-cost bulk raw materials dumped in large quantities. The group maintains stable annual chondroitin sulfate procurement of 36 tons.
Previously, the group sourced customized shark-derived chondroitin sulfate from French pharmaceutical manufacturers year-round. Driven by surging European raw material prices, shrinking local production capacity, and extended delivery cycles of 102 days, the group launched a domestic raw material substitution procurement project in 2025. It independently sourced pharmacopoeia-grade raw materials from three leading domestic chondroitin sulfate manufacturers, yet three systematic technical failures emerged during mass production on its automated production lines after raw material delivery: sustained-release tablet delamination and cracking, unqualified in-vitro dissolution curves of enteric-coated softgels, and flocculent turbidity precipitation of oral liquids under low-temperature storage. Five consecutive batches of pilot finished products were fully scrapped, resulting in raw material and auxiliary material losses exceeding EUR 73,000 and delayed new product launch schedules. The client repeatedly contacted the technical departments of supplying manufacturers for assistance, yet domestic production enterprises only focus on raw material extraction and purification control, with limited expertise in downstream overseas formulation logic and terminal mass production processes. They could only slightly adjust basic raw material content, failing to resolve finished product manufacturing failures from dimensions of formulation compatibility, powder modification, and parameter matching. Multiple manufacturers only emphasized compliance of their raw materials with national standards and basic USP indicators, declining in-depth technical assistance under the pretext that terminal formulation issues fell outside their service scope. Trapped in technical deadlock, the client fully entrusted HiSiaddi, a foreign trade service provider, to resolve technical pain points one by one through raw material indicator optimization, downstream fine-tuning of formulations, and mass production process improvement relying on its raw material physical and chemical database and formulation engineer resources, delivering a modified raw material scheme compatible with the client’s proprietary formula and supporting production guidance.
Original mandatory raw material benchmarks for the client’s finished product formulations: Shark cartilage-extracted chondroitin sulfate with content ≥95.0%, weight-average molecular weight 21,000 Da±1,500 Da, free protein ≤0.8%, compatible for simultaneous production of three product dosage forms.
HiSiaddi’s technical team received unqualified finished products, delivered raw materials, and full-formula auxiliary material samples from the client, reproducing mass production failures through physical and chemical testing and small-scale trials to lock failure root causes categorized into raw material physical property defects, formulation ratio flaws, and unreasonable terminal process parameters.
The client’s tablet formula combined chondroitin sulfate, glucosamine, MSM, and microcrystalline cellulose via automated wet granulation and high-speed rotary tableting. Mass production suffered particle stratification, tablet cracking, hardness deviation exceeding ±5N per batch, and surface cracking after 30 days of storage. Trace testing identified root causes: excessively wide particle size distribution of domestic raw material powder with unbalanced coarse/fine particle ratios (fine powder proportion exceeding 32%) and high raw material moisture absorption causing localized caking during auxiliary material blending and uneven granulation moisture. The raw material’s inherent repose angle of 37.8° resulted in poor flowability; significant density disparity between the raw material and water-soluble auxiliary materials triggered material segregation during blending, forming the core driver of tablet delamination. Trace residual free protein in raw materials altered adhesive properties post-heated granulation, making tablets prone to cracking under compression. Domestic manufacturers only control content and ash indicators during factory release without particle fluidity and particle size grading testing, rendering them unable to predict hidden compatibility risks for downstream formulations.
The client’s softgels adopted enteric coating formulations requiring ≥85% dissolution within 45 minutes in pH 6.8 intestinal medium; multiple batches tested less than 67% dissolution at 60 minutes, with lagging active ingredient release violating Spanish pharmaceutical administration listing standards. Root causes included broad raw material molecular weight distribution with excessive high-molecular-weight polysaccharide fragments and trace residual inorganic salt impurities delaying capsule shell erosion and active ingredient dissolution. Additionally, deviation of the raw material’s sulfation ratio from the client’s formulation benchmark strengthened hydrogen bonding between polysaccharide molecules, triggering weak complexation reactions with capsule shell auxiliary materials and further inhibiting active ingredient release. Manufacturers only control average molecular weight without segmented molecular weight cutting, making raw materials incompatible with precise release requirements of enteric preparations.
The client’s oral liquids adopt a weak acid system with pH controlled between 4.1 and 4.3, passing room-temperature filling inspections yet developing white flocculent precipitates after 15 days of storage at 2–8°C, rendering products unmarketable in supermarkets. Testing confirmed small-molecule degraded polysaccharides and trace thermally unstable residual proteins in raw materials precipitated under weak acid and low-temperature conditions; insufficient water-solubility modification of domestic raw material polysaccharides reduced solubility in weak acid environments. Conventional domestic manufacturing processes lack low-temperature stability modification sections, producing raw materials adapted to neutral beverages rather than the client’s weak acid formulation storage conditions.
Technical staff from all three supplying manufacturers lacked formulation R&D expertise and could only adjust raw material content instead of targeted optimization of powder, molecular weight, and modification indicators, stalling technical rectification.
HiSiaddi assembled a dedicated team of raw material process engineers, formulation scientists, and on-site process guidance specialists, establishing a three-step rectification roadmap: prioritize raw material physical property modification → slightly optimize the client’s terminal formulation → adjust mass production equipment parameters, delivering targeted technical schemes for each of the three dosage forms.
Revised internal control indicators for chondroitin sulfate were redefined based on shared requirements of all three dosage forms, with manufacturers coordinated to add post-production modification sections to original production lines for four key raw material upgrades:
1. Particle size grading modification: Install air flow classification screening equipment to remove ultra-fine and oversized particles, controlling raw material D90 at 105 μm with fine powder proportion <12% and repose angle optimized to 30°±1°, drastically improving powder flowability to resolve material blending stratification;
2. Precise molecular weight cutting: Adopt nanofiltration membrane grading processes to intercept oversized molecular fragments and eliminate small-molecule degraded products, locking weight-average molecular weight at 21,000 Da±800 Da with a molecular weight distribution coefficient ≤1.4, narrowing molecular weight ranges to enhance enteric dissolution performance;
3. Deep impurity removal & protein control: Add three-stage resin adsorption refining to reduce free protein from original 1.1% to ≤0.7% and strictly limit ash content ≤2.2%, eliminating hidden low-temperature precipitation risks from impurities;
4. Low-temperature surface modification: Adopt low-temperature liquid-phase coating modification processes to boost raw material solubility in weak acid environments, ensuring no precipitation after 72 hours of storage at 6°C for compatibility with oral liquid weak acid systems.
HiSiaddi simultaneously issued full-item COA test reports for modified raw materials, with all physical and chemical indicators re-verified by SGS third-party testing.
Minor adjustments to auxiliary material ratios were implemented without altering core proportions of the client’s proprietary formula to avoid compatibility conflicts between raw materials and auxiliary materials:
1. Sustained-release tablet formulation optimization: Adjust ratios of microcrystalline cellulose and pregelatinized starch, add 5% dry binder to reduce overall system moisture absorption and minimize granulation moisture fluctuations; adjust lubricant addition timing to split feeding into two stages during blending for improved particle uniformity;
2. Enteric-coated softgel formulation optimization: Slightly adjust plasticizer ratios of enteric coating materials to match dissolution characteristics of modified raw materials and prevent complexation between raw materials and coating auxiliary materials;
3. Oral liquid formulation optimization: Add small dosages of food-grade chelating agents to complex trace metal ions in raw materials and further strengthen stability under low-temperature systems.
HiSiaddi dispatched technical specialists to remotely coordinate the client’s Spanish production workshop, adjusting key automated production line parameters item by item:
1. Tablets: Lower wet granulation drying temperature by 5°C, control particle moisture at 3.2%–3.8%, and adjust tableting spindle pressure in segments to reduce tablet hardness deviation per batch;
2. Softgels: Optimize temperature control parameters for capsule shell swelling and lower instantaneous heating temperatures during filling to prevent raw material thermal denaturation;
3. Oral liquids: Optimize sterilization temperature rise curves and adopt segmented low-temperature instantaneous sterilization to reduce polysaccharide thermal degradation.
Three batches of modified raw material samples were shipped to Spain, with the client conducting full-dosage-form pilot production using optimized formulations and processes: Tablets exhibited no delamination or cracking with hardness fluctuations within standard ranges; enteric-coated softgels delivered an average dissolution rate of 88.2% at 45 minutes complying with European Pharmacopoeia standards; oral liquids remained clear without precipitation after 60 days of refrigerated storage. All three dosage forms passed full-item testing at Spain’s AENOR laboratory, prompting the client to issue a technical rectification acceptance confirmation letter.
The annual 36-ton customized chondroitin sulfate order was split into seven monthly production batches. HiSiaddi conducted on-site pre-delivery sampling testing of physical and chemical indicators for each batch, alongside full sets of export compliance documents (USP, LFGB, TSE/BSE). Goods were shipped in batches from Qingdao Port to Barcelona Port with full customs clearance and warehouse receipt without quality discrepancies. The client restored full-capacity mass production across all production lines, launching the previously delayed new products onto Spanish and French markets as scheduled. Cost comparison: Comprehensive procurement costs fell by 23.8% versus raw materials previously imported from France, while ocean delivery cycles shortened from 102 days to 37 days.
1. ARTROCARE Group of Spain completely terminated procurement from European original manufacturers and fully switched its entire annual 36 tons of raw material demand to modified domestic supplies supplied by HiSiaddi. In the following year, the group put forward a new customization demand for small-molecule chondroitin sulfate specially used in pediatric medical food oral liquids, adding an annual procurement volume of 12.5 tons.
2. Drawing on the formulation compatibility experience accumulated through this round of technical rectification, HiSiaddi assisted its cooperative manufacturers in perfecting standardized production processes for graded chondroitin sulfate applicable to multiple dosage forms, and successfully secured two mid-to-high-end nutrition brands of equivalent market positioning in Portugal and Italy.
3. The client entrusted HiSiaddi to formulate pre-storage inspection standards for incoming raw materials. Small-scale dosage-form trials are conducted in advance for every batch of raw materials before factory delivery to predict potential risks, thus eliminating technical hazards in subsequent mass production at the source.
Most domestic chondroitin sulfate manufacturers mainly focus on raw material extraction and refining processes, adopting physical and chemical indicators specified by national standards and pharmacopoeias as factory release acceptance criteria. They lack expertise in downstream formulation R&D and terminal mass production processes. While they can guarantee individual indicators of raw materials meet standards, they fail to predict the cascading impacts of raw material physical properties on tablets, capsules and oral liquids.
Mid-to-high-end European and American medical food enterprises develop proprietary in-house formulas, where raw material physical properties are highly correlated with terminal formulations. Slight fluctuations in raw material physicochemical properties may lead to full production line scrapping. Clients who contact manufacturers independently often fall into a technical dilemma: "raw materials meet standard indicators, yet finished product mass production fails".
Breaking the traditional foreign trade model that merely matches buyers with raw material suppliers, HiSiaddi centers its business on full-chain technical services and connects the complete technical chain covering raw material production modification, downstream formulation optimization and terminal process guidance. It analyzes the root causes of production failures from a neutral perspective balancing both suppliers and buyers. On one hand, it helps mid-to-high-end European clients resolve mass production technical obstacles, recover economic losses and smoothly complete the substitution of domestic raw materials. On the other hand, it supports domestic manufacturers to optimize product portfolios, escape cut-throat homogenized low-price competition, and successfully enter the high-end European medical food raw material supply chain, achieving long-term win-win results for both sides of supply and demand.
If you require further consultation services for formulation optimization, please contact HiSiaddi customer service.
+86-13120989737 
info@hisiaddi.com 
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