HiSiaddi is an innovative foreign trade service provider driven by dual pillars of technology commercialization and cross-border trading. We have established a "1+2+3+4=1" service system and can supply succinic acid sourced directly from well-known original manufacturers. As a foreign trader with in-house R&D capabilities, HiSiaddi frequently proposes formulation optimization schemes and application improvement suggestions for succinic acid via technological cooperation with manufacturers and accurate market insight. Below is our technical consulting case on succinic acid formulation optimization.
Contact HiSiaddi customer service for more formulation optimization consulting services.
The buyer is BioPharma B.V. based in the Netherlands, a leading Western European enterprise specializing in mid-to-high-end pharmaceutical excipients. It produces oral sustained-release tablets and oral liquid buffering raw materials, supplying local Dutch pharmacy chains and high-end nutritional formulation factories in Belgium. Its products comply with EP Pharmacopoeia, USP, ICH impurity standards, LFGB and EU REACH regulations. The company long purchased bio-based fermented succinic acid imported from Germany, but switched to domestic Chinese bio-based succinic acid amid price hikes and supply shortages of overseas raw materials, with an annual planned procurement volume of 132 tons. After large-scale production trials, three critical manufacturing failures emerged continuously:
1. Abnormal sustained-release tablet disintegration: With identical formulations, tablets disintegrated excessively fast in the early stage yet exhibited delayed disintegration in the later stage, shifting drug release curves outside pharmacopoeia limits and resulting in scrapping of entire batches of formulations.
2. Turbidity and precipitation of oral liquids under low-temperature storage: Prepared buffer solutions developed fine white floccules after 30 days of refrigeration at 5°C, failing clarity standards for premium oral liquids.
3. Blockages in automated batching systems: Mixed coarse and fine particles plus moisture absorption and caking of fine powder frequently blocked feeding pipelines, triggering unplanned production line shutdowns for maintenance. Domestic succinic acid manufacturers only controlled physical and chemical indicators per national standards and mastered fermentation/synthesis processes, lacking knowledge of pharmaceutical formulation compatibility. Multiple adjustments to feeding ratios failed to fully eliminate failures, delaying the client’s new drug approval progress. The client entrusted HiSiaddi’s technical team to conduct full-dimensional troubleshooting and rectification covering raw material traceability, formulation improvement and workshop production control.
Collaborating with organic acid engineers and pharmaceutical formulation technicians and combining CNAS third-party test data, HiSiaddi identified three core root causes: excessive impurities, irregular crystal particle size distribution and residual free solvents in standard domestic succinic acid.
1. Unstable drug release in tablets: Simplified refining processes in standard succinic acid leave trace by-products fumaric acid and maleic acid, altering the buffering capacity of excipients. Irregular crystal sizes lead to inconsistent dissolution rates, disrupting tablet pore structures and causing erratic disintegration speeds.
2. Low-temperature precipitation and turbidity in oral liquids: Trace high-boiling residual solvents and minor heavy metal levels in raw materials precipitate slowly to form floccules within the weak acid buffer system of oral liquids under low-temperature conditions. Raw material purity of only 99.3% fell below the client’s internal pharmacopoeia threshold of ≥99.7%.
3. Caking and pipeline blockages during feeding: Standard products lack particle size classification, with an excessively high proportion of ultrafine powder and moisture content exceeding 0.35%. High humidity in the Dutch storage facility accelerates moisture absorption and agglomeration of powder, clogging automated feeding pipelines.
1. Cooperate with domestic bio-based succinic acid manufacturers to implement two-stage recrystallization and negative-pressure distillation impurity removal processes. Control succinic acid purity ≥99.78%, single content of fumaric acid/maleic acid ≤0.02%, and residual organic solvents within ICH Q3C limits.
2. Produce two dedicated crystal grades separately: ① 30–40 mesh dense large-particle crystals exclusively for sustained-release tablets to deliver uniform and stable drug release; ② 150-mesh airtight dried sterile ultrafine powder for oral liquids, with moisture strictly controlled ≤0.11% to resist moisture absorption and caking.
1. Sustained-release tablet formulation: Split succinic acid into two feeding stages — add 75% during granulation and the remaining 25% before tableting. Incorporate 0.05% pharmaceutical-grade anhydrous dicalcium phosphate into the formulation to build a balanced buffer system, stabilizing disintegration rates to match pharmacopoeia release curves.
2. Oral liquid formulation: Pre-dissolve succinic acid completely in sterile purified water at 35°C before mixing with other raw materials; add trace sodium citrate to adjust the buffer system and suppress impurity precipitation under low temperatures.
1. Pack raw materials uniformly in high-barrier vacuum aluminum film bags. Maintain workshop temperature at a constant 22°C and environmental humidity ≤52% during feeding.
2. Install simple screening devices at the front end of automated batching lines to block accidental large foreign particles causing blockages.
HiSiaddi delivered laboratory trial samples, pilot production materials and mass production test batches sequentially. The Dutch client conducted accelerated formulation stability tests across five consecutive mass production runs: tablet disintegration indicators fully complied with pharmacopoeia standards, oral liquids remained clear after 120 days of low-temperature storage, and feeding operated smoothly without blockages. Product scrap rates dropped from the original 30.7% to below 0.3%. The client finalized an annual framework procurement contract of 134 tons: 76 tons of 30–40 mesh tablet-specific crystals and 58 tons of 150-mesh oral liquid ultrafine powder, split into 10 monthly production batches. HiSiaddi provided Dutch-English bilingual COA, EP pharmacopoeia test reports, REACH-compliant SDS and bio-based traceability documents, enabling smooth customs clearance and warehousing at Rotterdam Port. The client expanded into the Danish high-end formulation market the following year and placed an additional 39-ton succinic acid procurement order.
1. Mid-to-high-end Dutch pharmaceutical enterprise: The cost of customized domestic succinic acid decreased by 27.2% compared with German imported raw materials, supporting successful EU pharmaceutical authority filing and launch of new products. Raw material acceptance standards compiled by HiSiaddi enabled the enterprise to establish internal incoming succinic acid specifications, cutting formulation adjustment cycles for new raw materials by 55%.
2. Domestic manufacturer: The high-end European order drove completion of refined and graded crystallization production lines for pharmaceutical-grade succinic acid. The factory later secured designated procurement contracts from pharmaceutical enterprises in Switzerland and Finland, successfully entering the supply chain for high-end Nordic pharmaceutical excipients.
3. HiSiaddi Foreign Trade Service Provider: Our integrated technical service covering raw material process optimization, formulation adjustment and on-site workshop guidance deepened long-term cooperation with mid-to-high-end European pharmaceutical enterprises, forming differentiated service advantages in the bio-based succinic acid category.
Most domestic succinic acid manufacturers prioritize mass production of bulk food-grade and industrial-grade products manufactured to national standards, lacking refined impurity removal and particle size screening processes for pharmaceutical-grade materials, and possessing limited expertise in downstream formulation applications. Mid-to-high-end European and American pharmaceutical enterprises adhere to strict pharmacopoeia and ICH control rules, where minor deviations in trace impurities or particle sizes of raw materials can lead to full batch scrapping of formulations. As an independent foreign trade service provider, HiSiaddi breaks technical barriers between upstream production processes and downstream formulation development, implementing synchronous multi-link optimization of raw materials, formulations and production processes to support domestic high-end succinic acid in replacing imported alternatives within the European high-end market.
Contact HiSiaddi customer service for more formulation optimization consulting services.
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