Poloxamers Explained: A Comprehensive Guide to Non-Ionic Block Copolymer Surfactants
Poloxamers Explained: A Comprehensive Guide to Non-Ionic Block Copolymer Surfactants
What they are (definition & origin)
Poloxamers are amphiphilic triblock copolymers with the general formula HO–(EO)_a–(PO)_b–(EO)_a–H (EO = ethylene oxide, PO = propylene oxide). In water they self-assemble into micelles and, for some grades at sufficient concentration, form thermoreversible gels. Commercial families include BASF’s Pluronic/Kolliphor P, Croda’s Synperonic PE, and the USP/INN name poloxamer (e.g., poloxamer 188, 407).
Historically, these copolymers have been studied extensively since the 1990s (e.g., Alexandridis & Hatton’s classic review on EO–PO–EO surfactants in water and at interfaces).
About the CAS: 9003-11-6 is a generic registry entry for “oxirane, methyl-, polymer with oxirane,” i.e., EO/PO block copolymers — which poloxamers (and specific grades like P188 or P407) fall.
Composition, structure & naming
• Structure: symmetric PEO–PPO–PEO; hydrophobic PPO core flanked by hydrophilic PEO chains.
• USP definition: “Poloxamer is a synthetic block copolymer of ethylene oxide and propylene oxide,” with types defined by average molecular weight and % poly(ethylene oxide) (PEO).
Naming rules (two common conventions):
• Poloxamer Pabc (USP): ab × 100 ≈ PPO block MW; c × 10 ≈ wt% PEO.
Example: Poloxamer 188 → PPO ≈ 1,800; ~80% PEO. (USP table lists P188 81.8 ± 1.9% PEO.)
•
Pluronic F/L/P-xy (BASF): first one–two digits × 300 ≈ PPO MW; last digit × 10 ≈ wt% PEO; letter gives physical form at 25 °C (Liquid/Paste/Flake). Conventions differ slightly across brands, but both encode PPO size and PEO content.
Here is an example of Naming and Synonyms for Poloxamer 188, which helps to understand naming rules, all four names correspond to the same underlying chemistry (EO–PO–EO triblock with PPO ~1,800; ~80% PEO). The differences reflect supplier and application context (compendial vs industrial vs pharma vs Croda branding).
Naming and Synonyms for Poloxamer 188
Name / Code | Owner / Context | Meaning | Notes / Application |
Poloxamer 188 | USP / Ph.Eur. / INN | Compendial (generic) name; “188” encodes PPO ~1,800 and ~80% PEO | Used in pharmacopeias, regulatory documents (FDA IID, USP–NF) |
Pluronic® F-68 | BASF (industrial brand) | “F” = Flake/solid form; “68” encodes PPO size & %PEO | Original BASF trademark for this chemistry |
Kolliphor® P 188 | BASF (pharma/bioprocess brand) | Pharma-grade branding of Pluronic F-68 | Used in injectables, ophthalmics, and cell culture media |
Synperonic™ PE/F68 | Croda | “PE” = polyethylene–polypropylene block copolymer family; “F68” aligned with BASF code | Croda’s brand for the same composition |
Core physicochemical properties (and why they matter)
Self-assembly & gelation
· CMC & CMT:
Micellization occurs above a critical micelle concentration (CMC) and critical micellization temperature (CMT). CMC decreases with increasing PPO length and temperature, and increases with salts/solvent modifiers or shorter PPO. Reported values vary with method and conditions (hence ranges are expected).
Typical data (illustrative): Poloxamer 188 (F-68) CMC ~0.04 mM at 20–25 °C; other sources report higher (~0.48 mM) depending on method/grade. Poloxamer 407 (F-127) exhibits very low CMC (tens of µM); it also thermogels at ~15–30% w/w.
· Micelle size & morphology:
Micelles are typically 10–100 nm hydrodynamic diameter (grade- and condition-dependent). Aggregation number and size increase with temperature and PPO content — key for drug solubilization capacity.
· Thermogelling (notably P407):
Above sol-gel transition temperature (T_sol→gel usually near room/body temperature for 18–25% P407), solutions form reversible gels — strategic for in-situ forming depots.
Interfacial activity & HLB（Hydrophilic–Lipophilic Balance）
• HLB increases with PEO content (more hydrophilic).
Example: P407 HLB ~18–23; P188 HLB often quoted ≥24–29 — useful for choosing emulsifier vs wetting/solubilizer roles.
Cloud point & solubility
• High-EO grades (e.g., P188) have cloud point > 100 °C at typical use concentrations—i.e., excellent aqueous clarity over normal processing temperatures.
Stability & impurities
• Pharmaceutical/bioprocess grades are often stabilized with BHT (~50–150 ppm); labeling of any antioxidant is required by USP. Lot-to-lot polydispersity and trace species can affect performance, especially in cell culture.
Below are widely used, pharmacopeial poloxamers (all within the generic CAS 9003-11-6)：
• Poloxamer 188 = Pluronic F-68 = Kolliphor® P 188 = Synperonic PE/F68
Solid (flakes/prills). %PEO ≈ 81.8 ± 1.9; typical MW 7,680–9,510. HLB ≥ 24–29; Cloud point > 100 °C. Widely used as solubilizer, shear protectant in cell culture.
• Poloxamer 407 = Pluronic F-127 = Kolliphor® P 407 = Synperonic PE/F127
Solid; MW ~12,000–14,000; ~70% PEO; thermogelling at ~15–30% w/w; common in in-situ gels and topical/otic/ophthalmic forms.
• Poloxamer 338 = Pluronic F-108
MW ~14,000–15,000; ~80% PEO; (very high %PEO; hydrophilic solid) — used where very high HLB and viscosity building are desired.
• Poloxamer 184 = Pluronic L-64
MW ~2,900–3,100; ~40% PEO; cloud point 42–46 °C; (lower %PEO; liquid); more hydrophobic — useful for wetting/oil solubilization and as a co-surfactant.
• Poloxamer 84= Pluronic® P-84=Synperonic™ P84
MW ~4,000; ~40–50% PEO; intermediate hydrophilicity; liquid/paste form; Emulsifier and wetting agent in industrial & pharma formulations
Poloxamers with various Grade & purity carried by Aladdin
Aladdin catalog | Product name | Grade & Purity |
Poly(ethylene glycol)-block-poly(propylene glycol) -block-poly(ethylene glycol) | average Mn ~1,100(EO：PO=10:1) | |
Synperonic® PE P105 | surfactant | |
Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) | average Mn ~4,400(30%PEG) | |
Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) | average Mn ~2,000(EO：PO=1：9) | |
Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) | average Mn ~14,600(EO：PO=8：2) | |
Poly(propylene glycol)-block-poly(ethylene glycol)-block-poly(propylene glycol) | Average Mn~2700 (EO: PO=3: 7) | |
Poly(propylene glycol)-block-poly(ethylene glycol)-block-poly(propylene glycol) | average Mn ~2,000 | |
Kolliphor® P 188 |
| |
Poly(propylene glycol)-block-poly(ethylene glycol)-block-poly(propylene glycol) | average Mn ~3,300 | |
Poloxamer 407 | purified, non-ionic | |
Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) | average Mn ~5800(EO：PO=3：7) | |
Synperonic® F 108 | surfactant, non-ionic | |
Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) | average Mn ~2,900(EO：PO=2：3) | |
Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) | average Mn ~2,800 | |
Kolliphor® P 188 Micro |
| |
Kolliphor® P 407 | Ethylene oxide 71.5–74.9% | |
Kolliphor® P 407 Micro |
| |
Pluronic® F-127 | BioReagent, for cell culture, granular waxy form | |
Synperonic® PE/P84 |
| |
Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) | average Mn ~8,400(EO：PO=4：1) | |
Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) | average Mn ~12,600(EO：PO=7：3) |
How properties influence use (summary “design” guidance)
• Need shear protection/defoaming in bioreactors or high clarity in solutions?
→ pick high-EO, high-HLB grades (e.g., P188).
• Need in-situ gelling depot or prolonged residence?
→ P407 near 18–25% w/w; tune gel point with blends (e.g., add P188 or polysaccharides).
• Need oil solubilization/emulsification in topical/otic/ophthalmic?
→ match PPO size to payload hydrophobicity; consider mixed micelles with a more hydrophobic Pluronic (e.g., P123) for capacity.
• For parenterals,
→ check preservative compatibility (phenol/cresol can alter micelles) and sterilization effects (especially for P407 gels).
Poloxamers: Advantages vs Limitations
Advantages / Special Features | Limitations / Cautions |
Amphiphilic versatility: EO–PO–EO triblock structure allows micellization, emulsification, defoaming, solubilization, and gel formation depending on grade and concentration. | Batch-to-batch variability: As UVCB substances (complex mixtures), poloxamers can vary in MW distribution, hydroxyl value, cloud point, and performance — critical in bioprocesses and regulated pharma use. |
Wide grade spectrum: Different codes (e.g., P188, P407, P84, P184) cover a broad range of molecular weights, hydrophilic-lipophilic balance (HLB), and functions. | Method-dependent CMC/CMT: Critical micelle concentration/temperature values vary widely across measurement methods, solvents, and ionic conditions; must be determined under formulation-relevant conditions. |
Biocompatibility & regulatory acceptance: Listed in USP/Ph.Eur., present in FDA IID; generally safe, non-ionic, low toxicity; used in approved drugs (e.g., OTIPRIO® with P407). | Sterilization sensitivity: Heat sterilization and gamma irradiation can alter P407 gelation and rheology; validation required for parenteral/injectable systems. |
Protein & cell protection: Poloxamer 188 (F68) protects therapeutic proteins from aggregation and mammalian cells from shear damage in bioreactors. | Stabilizers & impurities: Many grades contain BHT (~50–150 ppm); not always acceptable in sensitive formulations. Lot variability in residual monomers or stabilizers may affect biopharma quality. |
Thermoresponsive gelation: Poloxamer 407 forms in situ gels at body temperature — used for long-acting ocular, nasal, rectal, and injectable drug delivery. | Preservative interactions: Phenol and m-cresol can cause micelle aggregation or turbidity in P188 solutions; requires compatibility testing in parenterals. |
Foam control & wetting: Mid-range grades (e.g., P84, P184/L64) are excellent antifoams and wetting agents in industrial fermentations, pulp/paper, and metalworking. | Cloud point sensitivity: Some grades (e.g., P184/Poloxalene) have relatively low CP (≈42–46 °C) and risk phase separation if storage/processing temperatures approach this range. |
Solubilization power: High-PEO grades (P188, P338) solubilize poorly water-soluble drugs and nutraceuticals, stabilize emulsions, and improve bioavailability. | Dose/route caveats: Generally safe as excipients, but very high systemic doses (esp. P407 in rodents) induce hyperlipidemia; safe margins must be respected. |
Versatility across industries: Used in pharma, bioprocessing, cosmetics, food, and industrial formulations — one surfactant class serving multiple sectors. | Environmental & cost considerations: As synthetic polymers, poloxamers are petrochemical-derived, not biodegradable at the same rate as natural surfactants; cost is higher than commodity surfactants. |
References:
1. United States Pharmacopeia. Poloxamer monograph. USP–NF Online. United States Pharmacopeial Convention; 2023.
2. United States Pharmacopeia. Poloxamer: compendial table of types. USP–NF Online. United States Pharmacopeial Convention; 2023.
3. European Pharmacopoeia. Poloxamers. European Directorate for the Quality of Medicines & HealthCare; 2023.
4. U.S. Food and Drug Administration. Inactive Ingredient Database (IID): Poloxamer entries. FDA; 2023.
5. Chemical Abstracts Service (CAS). Registry entry 9003-11-6: Oxirane, methyl-, polymer with oxirane. ChemIDplus/NIST/EPA SRS; 2023.
6. Alexandridis P, Hatton TA. Poly(ethylene oxide)–poly(propylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling. Colloids Surf A Physicochem Eng Asp. 1995;96(1–2):1-46.
7. Rieger J, van der Linden M. Poloxamers and related triblock copolymers: nomenclature, micelles, and applications. Polym Chem. 2011;2(3):587-97.
8. Schmolka IR. Artificial skin. I. Preparation and properties of pluronic F-127 gels for treatment of burns. J Biomed Mater Res. 1972;6(6):571-82. (Example of early P407 thermogel work.)
9. BASF. Kolliphor® P 188 technical information sheet. BASF SE; 2022.
10. BASF. Kolliphor® P 407 technical information sheet. BASF SE; 2022.
11. BASF. Poloxamers in biopharmaceutical upstream processing. Technical brochure. BASF SE; 2022.
12. Croda International. Synperonic™ PE/F68 and Synperonic™ PE/F127 product data sheets. Croda; 2022.
13. Sigma-Aldrich/Merck. Poloxamer 188 (Pluronic F68) product information. MilliporeSigma; 2022.
14. Sigma-Aldrich/Merck. Poloxamer 407 (Pluronic F127) product information. MilliporeSigma; 2022.
15. SERVA Electrophoresis. Poloxamer 188 datasheet. SERVA; 2021.
16. U.S. Food and Drug Administration. OTIPRIO® (ciprofloxacin otic suspension) NDA approval package. FDA; 2015.
17. Roscigno R, et al. Effect of preservatives on micellization of poloxamer 188. Int J Pharm. 2018;548(1):214-22.
18. Ricci EJ, Lunardi LO, Nanclares DM, Marchetti JM. Sustained release of lidocaine from poloxamer 407 gels. Int J Pharm. 2005;288(2):235-44.
19. Mortensen A, et al. Poloxamer 407 as a model for hyperlipidemia in rats: mechanisms and outcomes. Atherosclerosis. 2001;156(1):9-19.
Aladdin: https://www.aladdinsci.com/