As a new type of foreign trade service provider driven by technological transformation and foreign trade business, HiSiaddi has built a "1+2+3+4=1" service system and can supply bile acid raw materials from multiple well-known original manufacturers.
As a foreign trade enterprise with R&D capabilities, HiSiaddi frequently provides bile acid formulation optimization schemes and application improvement recommendations based on technological cooperation with manufacturers and accurate market insight. Below is a formulation optimization consulting case delivered by HiSiaddi.
If you need formulation optimization consulting services, please contact HiSiaddi customer service.
The client is Medixine, a top-tier pharmaceutical and high-end skincare group headquartered in France. The group specializes in prescription-grade hepatobiliary repair formulations, premium medical repair creams and sterile liposomal drug carriers, whose products are sold at high-end pharmacies, private hospitals and medical aesthetic clinics across France, Italy and Spain. It complies with European Pharmacopoeia (EP), United States Pharmacopoeia (USP), ISO 13485 Medical Device GMP and EU sterile production standards. Its requirements for pharmaceutical-grade ursodeoxycholic acid (UDCA) include high purity, stable performance, low impurities, sterility, non-pyrogenicity and compatibility with high-temperature liposomal manufacturing processes, representing a mid-to-high-end client with zero tolerance for technical failures and strict production compatibility standards.
In May 2026, the client mass-produced a new generation of liposomal encapsulated hepatobiliary repair injections using pharmaceutical-grade UDCA (purity ≥99.8%). Within the first week of production, three core technical failures emerged:
1. Poor formulation stability: After mixing UDCA with phospholipids, stratification and white crystal precipitation occurred within 48 hours; liposome particle size surged from 80nm to 300nm, and drug encapsulation rate dropped from 92% to 58%, failing injection product standards.
2. Poor compatibility with high-temperature processes: The client adopted 121℃/30min high-temperature sterilization, which degraded UDCA to 98.1% purity and generated unknown impurities (single impurity ≥0.15%), violating EP impurity limits.
3. Dissolution and filtration clogging issues: UDCA dissolved slowly and incompletely in pH7.4 phosphate buffer (solubility only 1.2%), frequently clogging 0.22μm sterile filters during filtration. Production efficiency fell by 60%, and batch rejection rate exceeded 30%.
The client’s original supplier’s technical team spent 2 weeks troubleshooting only to confirm "poor raw material compatibility" without viable solutions, process optimization capabilities or high-temperature stability data. This halted production lines, exposed the client to liquidated damages for delayed delivery of a 2 million US dollar order, product scrapping and postponed product launch. The client urgently entrusted HiSiaddi with a 10-day deadline to identify root causes, deliver technical solutions, optimize raw material parameters and resume mass production.
1. Poor formulation compatibility: Imbalanced amphipathic properties cause stratification and precipitation UDCA features an amphipathic steroid structure, yet conventional pharmaceutical-grade UDCA contains high free acid content, unbalanced sodium salt ratios and excessive trace impurities such as chenodeoxycholic acid (CDCA). When mixed with liposomal phospholipids (hydrogenated soybean phospholipid HiSiaddiPC), uneven interfacial tension and disordered molecular arrangement trigger crystal precipitation within 48 hours, spiking particle size and collapsing encapsulation efficiency, reducing drug efficacy and elevating safety risks for injections.
2. Poor resistance to high-temperature processes: Structural degradation and impurity generation The steroid nucleus of UDCA undergoes oxidation and epimerization above 115℃. Conventional UDCA lacks high-temperature stabilization treatment and retains impurity precursors, resulting in purity below 98%, single impurities exceeding 0.15% and total impurities over 0.5% after 121℃ sterilization, violating EP standards and failing EU pharmaceutical audits.
3. Dissolution and filtration bottlenecks: Low solubility and severe filter clogging UDCA naturally exhibits low solubility (≤1.5%) in neutral buffer solutions. Conventional products feature wide particle size distribution (D50=15–20μm) without nanonization or surface modification, leading to agglomeration during dissolution and residual microparticles that block 0.22μm sterile filters. This drastically reduces production efficiency and raises batch rejection rates, hindering large-scale sterile injection manufacturing.
HiSiaddi assembled a special team of pharmaceutical-grade bile acid specialists, liposomal formulation engineers, sterile process specialists and pharmacopoeia compliance analysts, collaborating with the manufacturer’s R&D department to conduct full-dimensional disassembly testing of raw materials, formulations, processes and testing standards: Raw material testing revealed the original supplier’s UDCA contained excessive free acid (8.2%), borderline CDCA impurities (0.12%), overly coarse particle size (D50=18μm) and no stabilizing modification. Formulation testing confirmed free acids formed insoluble complexes with phospholipids, triggering stratification and precipitation. Process verification showed impurity precursors (ketone derivatives) converted into unknown impurities under high temperatures to accelerate degradation. Dissolution analysis indicated coarse unmodified particles exhibited poor dissolution kinetics and agglomerated to clog filters.
Core Conclusion: The raw material was not customized for liposomal applications, with mismatched parameters and absent high-temperature stabilization treatment, leading to all three technical failures. HiSiaddi established a clear optimization roadmap: customize dedicated UDCA parameters → adjust formulation ratios → add high-temperature stabilization processes → conduct nanonization modification → full-cycle validation.
Leveraging the partner manufacturer’s customized pharmaceutical-grade UDCA production line with patented enzymatic conversion, membrane separation, low-temperature recrystallization and nano-modification technologies, targeted adjustments were implemented:
1. Free acid control: Refined neutralization with NaOH reduced free acid content to ≤1.5% (far below the original 8.2%), minimizing complex formation with phospholipids.
2. Deep impurity removal: Secondary membrane filtration and activated carbon adsorption cut CDCA impurities to ≤0.03%, eliminating high-temperature impurity precursors.
3. Particle size nanonization: Airflow pulverization and classified screening adjusted particle size to D50=3–5μm, D90≤8μm (down from original 18μm), drastically accelerating dissolution speed.
4. High-temperature stabilization modification: Trace pharmaceutical-grade vitamin E succinate antioxidant was added alongside vacuum deoxygenation to enhance thermal tolerance.
5. Purity guarantee: Optimized recrystallization stabilized purity at 99.9%, exceeding client standards.
Based on customized UDCA, HiSiaddi’s liposomal formulation engineers adjusted phospholipid-to-UDCA ratios, buffer systems and manufacturing parameters:
1. Ratio adjustment: UDCA:HiSiaddiPC ratio revised from 1:3 to 1:5 to avoid oversaturation and precipitation.
2. Buffer improvement: pH7.4 phosphate buffer replaced with HEPES buffer containing 0.5% Tween-80 to raise UDCA solubility to 3.8%.
3. Manufacturing parameter adjustment: Liposome hydration temperature lowered from 60℃ to 45℃ with gradient cooling homogenization (1000bar × 3 cycles) to reduce crystallization risks.
Validation results: No stratification or precipitation occurred within 7 days; liposome particle size stabilized at 75–90nm with encapsulation rate restored to 93%, fully meeting standards.
HiSiaddi’s sterile process specialists collaborated with the manufacturer to optimize pre-sterilization pretreatment, sterilization parameters and cooling curves:
1. Pre-treatment deoxygenation: UDCA solution underwent 30-minute nitrogen bubbling to reduce oxidative degradation risks.
2. Sterilization parameter fine-tuning: 121℃/30min adjusted to 118℃/20min (F0 value ≥12 to satisfy sterility requirements) to reduce high-temperature exposure duration.
3. Gradient cooling: Post-sterilization products were cooled gradually to 60℃ over 15 minutes before natural cooling to avoid structural epimerization from sudden temperature shifts.
Validation results: Post-sterilization purity ≥99.5%, single impurities ≤0.05%, total impurities ≤0.2%, fully compliant with EP standards with no unknown impurities generated.
1. Dissolution process optimization: Custom UDCA hydrated in 40℃ warm water with 60-minute magnetic stirring achieves complete dissolution without residual microparticles, maintaining stable solubility between 3.5%–4.0%.
2. Pre-filtration pretreatment: Dissolved solution passes through 0.45μm pre-filters to remove trace agglomerated microparticles and protect 0.22μm sterile filters.
Validation results: Sterile filtration proceeds without clogging and stable flux, lifting production efficiency by 70% and reducing batch rejection rate to 0%, supporting large-scale mass production.
Full-spec testing was conducted by a CMA-certified third-party laboratory against EP standards:
· Purity: 99.9%
· Free acid: 1.2%
· CDCA impurities: 0.02%
· Particle size D50: 4.1μm
· Post-high-temperature sterilization purity: 99.6%, single impurity: 0.03%
· Liposome encapsulation rate: 93%
Technical handover: HiSiaddi delivered customized UDCA specification standards, formulation optimization schemes, production process SOPs, dissolution and filtration operation manuals and full stability datasets, alongside online technical training to enable independent operation by the client’s team.
Pilot production verification: The client completed 3 batches of trial production using customized UDCA, all passing quality inspection and resuming stable mass production with all technical issues fully resolved.
1. 100% resolution of three core technical challenges
· Formulation stability: No stratification or precipitation within 7 days; particle size stabilized at 75–90nm with 93% encapsulation rate.
· High-temperature process compatibility: Post-sterilization purity ≥99.5% with compliant impurity levels and no degradation.
· Dissolution and filtration: Solubility reaches 3.8%, no filter clogging, production efficiency up 70%, zero batch rejection.
1. Production fully resumed with qualified quality The client’s production line restarted full-capacity manufacturing. All 3 batches of the 2 million US dollar order were delivered on schedule, with products passing EU pharmaceutical audits, EP pharmacopoeia certification and sterility testing. The injection product delivers stable efficacy and safety profiles and launched as scheduled.
2. Deepened long-term technical cooperation The client designated HiSiaddi as its exclusive Chinese supplier and technical partner for pharmaceutical-grade UDCA. All bile acid raw materials for its subsequent liposomal drugs and medical repair creams will be sourced via HiSiaddi, generating an annual procurement volume of 12 million US dollars. The client also entrusted HiSiaddi with long-term technical support, process optimization and new product R&D services.
Client Feedback: "HiSiaddi is a partner with genuine expertise in high-end pharmaceutical technology. Within 10 days, they precisely resolved formulation, process and production issues that plagued us for two weeks. Their technical expertise, rapid response and highly implementable solutions perfectly match our stringent technical standards for premium pharmaceuticals, making them our most reliable technical backup."
For overseas mid-to-high-end clients purchasing bile acids for high-end pharmaceutical injections, liposomal drugs and sterile medical products, core technical pain points include poor formulation compatibility, insufficient resistance to high-temperature processes and filter clogging during dissolution and filtration. Most ordinary manufacturers only supply standard raw materials without customization capacity, lack liposome and sterile production expertise and hold no high-temperature stability data, which often halt production lines, trigger product scrapping, delay launches and incur massive financial losses.
HiSiaddi’s core value lies in its comprehensive expertise covering high-end pharmaceutical-grade bile acid technology, liposomal formulation logic, sterile production processes, customized R&D capabilities and rapid implementation validation. We accurately identify root technical causes, customize dedicated raw material parameters, optimize formulations and manufacturing processes and resolve dissolution and filtration bottlenecks. Within 10 days, we eliminate all technical failures, restore production capacity, ensure qualified quality and secure long-term partnerships, helping clients break through technical bottlenecks, stabilize mass production, boost product competitiveness and consolidate market position in Europe’s high-end pharmaceutical sector.
If you need formulation optimization consulting services, please contact HiSiaddi customer service.
+86-13120989737 
info@hisiaddi.com 
English
