Lee YC, Simamora P, Yalkowsky SH. Effect of Brij-78 on systemic delivery of insulin from an ocular device. J Pharm Sci 1997; 86(4): 430–433.

Sawicki W, Janicki S. Influence of polyoxyethylene-10-oleylether on in vitro verapamil hydrochloride penetration through mucous membrane from model buccal drug formulation. STP Pharma Sci 1998; 8(2): 107–111.

Al Gohary OM, Foda NH. Pharmaceutical and microbiological aspects of nalidixic acid suppositories. Egyptian J Pharm Sci 1996; 37(1–6): 273–284.

El Assasy AH, Foda NH, Badawi SS, Abd-El-Rehim RT. Formulation of flurbiprofen suppositories. Egyptian J Pharm Sci 1995; 36(1–6): 31–53.

El Assasy AH, Foda NH, Badawi SS, Abd-El-Rehim RT. Release characteristics and bioavailability of pirprofen from suppository bases. Egyptian J Pharm Sci 1995; 36(1–6): 15–29.

Harmia-Pulkkinen T, Ojantakanen S. In vitro release kinetics of timolol and timol oleate from polyethylcyanoacrylate nanoparti- cles. Part 2. Nanoparticles manufacture with timolol maleate using different surfactants and organic solvents. Acta Pharm Fenn 1992; 101(2): 57–63.

Muller RH, Wallis KH, Troster SD, Kreuter J. In vitro characterization of poly(methyl-methacrylate) nanoparticles and correlation to their in vivo fate. J Control Release 1992; 20: 237– 246.

Troster SD, Muller U, Kreuter J. Modification of the body distribution of poly(methylmethacrylate) nanoparticles in rats by coating with surfactants. Int J Pharm 1990; 61: 85–100.

Cabrera J, Redondo P, Becerra A, et al. Ultrasound-guided injection of polidocanol microfoam in the management of venous leg ulcers. Arch Dermatol 2004; 140(6): 667–673.

Brisaert MG, Everaerts I, Plaizier-Vercammen JA. Chemical stability of tretinoin in dermatological preparations. Pharm Acta Helv 1995; 70(2): 161–166.

Azaz E, Donbrow M, Hamburger R. Incompatibility of non-ionic surfactants with oxidizable drugs. Pharm J 1973; 211: 15.



McDonald C, Richardson C. The effect of added salts on solubilization by a non-ionic surfactant. J Pharm Pharmacol 1981; 33: 38–39.

The Registry of Toxic Effects of Chemical Substances. Atlanta, GA: National Institute for Occupational Safety and Health, 2000.

General References

Ammar HO, Khali RM. Solubilization of certain analgesics by Cetomacrogol 1000. Egypt J Pharm Sci 1996; 37: 261–271.

Elworthy PH, Guthrie WG. Adsorption of non-ionic surfactants at the griseofulvin-solution interface. J Pharm Pharmacol 1970; 22 (Suppl.): 114S–120S.

Guveli D, Davis SS, Kayes JB. Viscometric studies on surface agent solutions and the examination of hydrophobic interactions. J Pharm Pharmacol 1974; 26 (Suppl.): 127P–128P.

Malcolmson C, Satra C, Kantaria S, et al. Effect of oil on the level of solubilization of testosterone propionate into non-ionic oil-in-water microemulsions. J Pharm Sci 1998; 87: 109–116.

Vasiljevic D, Vuleta G, Dakovic LJ, Primorac M. Influence of emulsifier concentration on the rheological behavior of w/o/w multiple emulsions. Pharmazie 1994; 49: 933–934.

Walters KA, Dugard PH, Florence AT. Non-ionic surfactants and gastric mucosal transport of paraquat. J Pharm Pharmacol 1981; 33: 207–213.

Authors

RR Gupta, KK Singh.

Date of Revision

5 August 2005.

Polyoxyethylene Castor Oil Derivatives

Nonproprietary Names

BP: Polyoxyl castor oil

Hydrogenated polyoxyl castor oil PhEur: Macrogolglyceroli ricinoleas

Macrogolglyceroli hydroxystearas USPNF: Polyoxyl 35 castor oil

Polyoxyl 40 hydrogenated castor oil Polyoxyethylene castor oil derivatives are a series of materials obtained by reacting varying amounts of ethylene oxide with either castor oil or hydrogenated castor oil. Several different types of material are commercially available, the best-known being the Cremophor series (BASF Corp.). Of these, two castor oil derivatives are listed in the PhEur 2005 and USPNF 23.

See also Sections 2, 3 and 4.

Synonyms

Synonyms applicable to polyoxyethylene castor oil derivatives are shown below. See Table I for information on specific materials.

Acconon; Arlatone; Cremophor; Etocas; Eumulgin; Jee- chem; Lipocol; Mapeg; Marlowet; Nikkol; Protachem; Simul- sol.

Table I: Synonyms of selected polyoxyethylene castor oil derivatives.

Name Synonym

Polyoxyl 5 castor oil Acconon CA-5; castor oil POE-5; Etocas 5;

Hetoxide C-5; Jeechem CA-5; PEG-5 castor oil; polyoxyethylene 5 castor oil.

Polyoxyl 9 castor oil Acconon CA-9; castor oil POE-9; Jeechem CA-

9; PEG-9 castor oil; polyoxyethylene 9 castor oil; Protachem CA-9.

Polyoxyl 15 castor oil Acconon CA-15; castor oil POE-15; Jeechem

CA-15; PEG-15 castor oil; polyoxyethylene 15 castor oil; Protachem CA-15.

Polyoxyl 35 castor oil Castor oil POE-35; Cremophor EL; Cremophor

ELP; Etocas 35; glycerol polyethyleneglycol ricinoleate; PEG-35 castor oil; polyethoxylated castor oil; polyoxyethylene 35 castor oil.

Polyoxyl 40 castor oil Castor oil POE-40; Cirrasol G-1284; Croduret

40; Etocas 40; Eumulgin RO; Hetoxide C40; Jeechem CA-40; Marlowet R40; Nikkol CO 40TX; Nonionic GR-40; PEG- 40 castor oil; polyoxyethylene 40 castor oil; Protachem CA-40.

Chemical Name and CAS Registry Number

Polyethoxylated castor oil [61791-12-6]

Empirical Formula and Molecular Weight

Polyoxyethylene castor oil derivatives are complex mixtures of various hydrophobic and hydrophilic components. Members

within each range have different degrees of ethoxylation (moles)/PEG units as indicated by their numerical sufffix (n).

Polyoxyl 40 hydrogenated castor oil

Cremophor RH 40; Croduret 40; Eumulgin HRE 40; glycerol polyethyleneglycol oxystearate; Hetoxide HC40; hydrogenated castor oil POE-40; Jeechem CAH-40; PEG-40 hydrogenated castor oil; polyethoxylated hydrogenated castor oil; polyoxyethylene 40 hydrogenated castor oil; Lipocol HCO-40; Lipocol LAV HCO 40; Nikkol HCO 40 Pharma; Nonionic GRH-40; Protachem CAH-40.

The chemical structures of the polyethoxylated hydrogenated

castor oils are analogous to polyethoxylated castor oils with the exception that the double bond in the fatty chain has been

Polyoxyl 60 castor oil Castor oil POE-60;Jeechem CA-60; Nikkol

CO 60TX; PEG-60 castor oil; polyoxyethylene 60 castor oil.

saturated by hydrogenation.

The PhEur 2005 states that polyoxyl castor oil contains mainly ricinoleyl glycerol ethoxylated with 30–50 molecules of ethylene oxide (nominal value), with small amounts of macrogol ricinoleate, and of the corresponding free glycols. The PhEur 2005 also states that polyoxyl hydrogenated castor

oil contains mainly trihydroxystearyl glycerol ethoxylated with

Polyoxyl 60

hydrogenated castor oil

Croduret 60; Eumulgin HRE 60; Hetoxide

HC60; hydrogenated castor oil POE-60; Jeechem CAH-60; PEG-60 hydrogenated castor oil; polyoxyethylene 60 hydrogenated castor oil; Lipocol HCO-60; Nikkol HCO 60 Pharma; Protachem CAH- 60.

7–60 molecules of ethylene oxide (nominal value).

In polyoxyl 35 castor oil (Cremophor EL), the relatively

hydrophobic constituents comprise about 83% of the total mixture, the main component being glycerol polyethylene

Polyoxyl 100 castor oil Hydrogenated castor oil POE-100; Jeechem

CA-100; PEG-100 hydrogenated castor oil; polyoxyethylene 100 hydrogenated castor oil.

glycol ricinoleate. Other hydrophobic constituents include fatty

acid esters of polyethylene glycol along with some unchanged castor oil. The hydrophilic part (17%) consists of polyethylene

Polyoxyl 100

hydrogenated castor oil

Cirrasol G-1300; Jeechem CA-100; Nikkol

HCO 100; polyoxyethylene 100 hydrogenated castor oil.

glycols and glycerol ethoxylates. Cremophor ELP, a ‘purified’ grade of Cremophor EL is also a polyoxyl 35 castor oil; it has a lower content of water, potassium, and free fatty acids and

Polyoxyl 200 castor oil Hetoxide C200; Jeechem CA-200;

polyoxyethylene 200 castor oil; PEG-200 castor oil; castor oil POE-200.

hence is claimed to have improved stability.

In polyoxyl 40 hydrogenated castor oil (Cremophor RH 40), approximately 75% of the components of the mixture are hydrophobic. These comprise mainly fatty acid esters of

Polyoxyl 200

hydrogenated castor oil

Hydrogenated castor oil POE-200; Jeechem

CAH-200; PEG-200 hydrogenated castor oil; polyoxyethylene 200 hydrogenated castor oil.

Polyoxyethylene Castor Oil Derivatives 573

glycerol polyethylene glycol and fatty acid esters of polyethy- lene glycol. The hydrophilic portion consists of polyethylene glycols and glycerol ethoxylates.

Structural Formula

See Section 4.

Functional Category

Emulsifying agent; solubilizing agent; wetting agent.

Applications in Pharmaceutical Formulation or Technology

Polyoxyethylene castor oil derivatives are nonionic surfactants used in oral, topical, and parenteral pharmaceutical formula- tions.

Polyoxyl 35 castor oil is mainly used as an emulsifing and solubilizing agent, and is particularly suitable for the produc- tion of aqueous liquid preparations containing volatile oils, fat- soluble vitamins, and other hydrophobic substances.(1,2) Cremophor EL emulsifies or solubilizes the fat-soluble vitamins A, D, E, and K in aqueous solutions for oral and topical administration. In 1 mL of a 25% v/v aqueous polyoxyl 35 castor oil (Cremophor EL) solution it is possible to incorporate approximately 10 mg of vitamin A palmitate; approximately 10 mg of vitamin D; approximately 120 mg of vitamin E acetate; or approximately 120 mg of vitamin K1.

In aqueous alcoholic solutions, it very readily solubilizes essential oils. Aqueous solutions of hydrophobic drugs (e.g. miconazole, hexetidine, clotrimazole, benzocaine) can also be prepared with Cremophor EL. Cremophor EL has also been used as a solubilizing agent for drugs like cyclosporin A,(3) paclitaxel,(4) and cisplatin.(5) Cremophor ELP is manufactured by purifying Cremophor EL and is therefore suitable for parenteral applications, e.g. Taxol preparations. In oral formulations, the taste of polyoxyl 35 castor oil (Cremophor EL) can be masked by a banana flavor.

Polyoxyl 35 castor oil (Cremophor EL) has also been used as a solvent in proprietary injections of diazepam, propanidid, and alfaxalone with alfadolone acetate; see Section 14. A self- microemulsifying drug delivery system (SMEDDS) for oral bioavailability, and the enhancement of halofantrine,(6) and simvastatin,(7) has been prepared using Cremophor EL. Cremophor EL has also been used as a buffering agent for aqueous tropicamide eyedrops.(8) It has also been used in an aqueous mixture together with caprylic/capric glyceride for mucosal vaccination, providing a potential alternative to parenteral vaccination.(9) It has also been used to enhance the permeability of peptides across monolayers of Caco-2 cells by inhibiting the apically polarized efflux system, enhancing intestinal absorption of some drugs.(10) Cremophor has been used as a vehicle for boron neutron-capture therapy in mice; which is a form of radiation therapy used in the treatment of glioblastoma multiforme.(11) Polyoxyl 35 castor oil is also used in the production of glycerin suppositories.

In veterinary practice, polyoxyl 35 castor oil can be used to emulsify cod liver oil, and oils and fats incorporated into animal feeding stuffs.

In cosmetics, polyoxyl 35 castor oil is mainly used as a solubilizing agent for perfume bases and volatile oils in vehicles containing 30–50% v/v alcohol (ethanol or propan-2-ol). In hand lotions, it can be used to replace castor oil.

Polyoxyl 40 hydrogenated castor oil may be used in preference to polyoxyl 35 castor oil in oral formulations since



it is almost tasteless. In aqueous alcoholic or completely aqueous solutions, polyoxyl 40 hydrogenated castor oil can be used to solubilize vitamins, essential oils, and certain drugs. Using 1 mL of a 25% v/v aqueous solution of polyoxyl 40 hydrogenated castor oil, it is possible to solubilize approxi- mately 88 mg of vitamin A palmitate, or approximately 160 mg of vitamin A propionate. Other materials that can be solubilized are alfadolone, alfaxalone, hexachlorophene, hex- etidine, levomepromazine, miconazole, propanidid, and thio- pental.

In aerosol vehicles that include water, the addition of polyoxyl 40 hydrogenated castor oil improves the solubility of the propellant in the aqueous phase. This enhancement applies both to dichlorodifluoromethane and to propane/butane mixtures.

Foam formation in aqueous ethanol solutions containing polyoxyl 40 hydrogenated castor oil can be suppressed by the addition of small amounts of polypropylene glycol 2000.

Polyoxyl 40 hydrogenated castor oil is also used as an emulsifier of fatty acids and alcohols.

Polyoxyethylene castor oil derivatives have been used experimentally as a surfactant for the controlled release matrix pellet formulation containing nanocrystalline ketoprofen,(12) and for the transdermal delivery of vinpocetin.(13)

Hydrogenated castor oil (HCO) derivatives containing more than 20 oxyethylene units were found to prolong the plasma circulation times of menatetrenone incorporated in lipid emulsions.(14) Polyoxl 60 hydrogenated castor oil has been reported to provide a self-microemulsifying system with enhanced oral absorption,(15) and a drastic reduction in plasma clearance of lipid emulsions.(16) It has been used in the formulation of liposomes,(17) and it has been suggested that more than 60% aids in the targeting of liposomes to the liver.(18) Also, polyoxyl 60 hydrogenated castor oil micellar solutions of cyclosporin A delivered the drug via the GI tract to the lymphatics with an extremely high selectivity.(19,20)

Cremophor RH 40 and RH 60 have been used as additives to enhance the drug release from suppository formula- tions.(21,22)

Description

Polyoxyl 35 castor oil occurs as a pale yellow, viscous liquid that is clear at temperatures above 268C. It has a slight but characteristic odor and can be completely liquefied by heating to 268C.

Polyoxyl 40 hydrogenated castor oil occurs as a white to yellowish, semisolid paste at 208C that liquefies at 308C. It has a very faint characteristic odor and is almost tasteless in aqueous solution.

Polyoxyl 60 hydrogenated castor oil occurs as a white paste at room temperature. It has little taste or odor in aqueous solution.

Pharmacopeial Specifications

See Table II.

Typical Properties

See Tables III, IV, and V.

Stability and Storage Conditions

Polyoxyl 35 castor oil (Cremophor EL and Cremophor ELP) forms stable solutions in many organic solvents such as

574 Polyoxyethylene Castor Oil Derivatives

Table II: Pharmacopeial specifications for polyoxyethylene castor oil derivatives.

 

Test PhEur 2005 USPNF 23    

Polyoxyl castor oil Polyoxyl hydrogenated castor oil Polyoxyl 35 castor oil Polyoxyl 40 hydrogenated castor oil    

Identification + + + +    

Characters + + — —    

Appearance of solution + + — —    

Alkalinity + + — —    

Relative density ≈1.05 — — —    

Specific gravity — — 1.05–1.06 —    

Congealing temperature Viscosity at 258C

Water —   500–800 mPa s

43.0% —

—

43.0% —  650–850 cP s

43.0% 16–268C

—

43.0%    

Total ash 40.3% 40.3% — —    

Residue on ignition — — 40.3% 40.3%    

Heavy metals 410 ppm 410 ppm 40.001% 40.001%    

Acid value

Hydroxyl value 42.0

+ 42.0

+ 42.0

65–80 42.0

60–80    

Dioxan

Free ethylene oxide Organic volatile impurities 410 ppm 41 ppm

— 410 ppm 41 ppm

— —

—

+ —

—

+  

chloroform, ethanol, and propan-2-ol; it also forms clear, stable, aqueous solutions. Polyoxyl 35 castor oil (Cremophor EL and Cremophor ELP) is miscible with other polyoxyethy- lene castor oil derivatives and on heating with fatty acids, fatty alcohols, and some animal and vegetable oils. Solutions of polyoxyl 40 hydrogenated castor oil (Cremophor RH 40) in aqueous alcohols are also stable.

On heating of an aqueous solution, the solubility of polyoxyl 35 castor oil (Cremophor EL and Cremophor ELP) is reduced and the solution becomes turbid. Aqueous solutions of polyoxyl hydrogenated castor oil (Cremophor RH grades) heated for prolonged periods may separate into solid and liquid phases on cooling. However, the product can be restored to its original form by homogenization.

Aqueous solutions of polyoxyl 35 castor oil (Cremophor EL and Cremophor ELP) are stable in the presence of low concentrations of electrolytes such as acids or salts, with the exception of mercuric chloride; see Section 12.

Aqueous solutions of polyoxyl 35 castor oil (Cremophor EL and Cremophor ELP) can be sterilized by autoclaving for 20 minutes at 1218C. In this process, a product may acquire a deeper color but this has no significance for product stability. Aqueous solutions of polyoxyl hydrogenated castor oil (Cremophor RH) can similarly be sterilized by autoclaving at 1218C, but this may cause a slight decrease in the pH value.

Although the method of manufacture used for polyoxyethy- lene castor oil derivatives ensures that they are near-sterile, microbial contamination can occur on storage.

Polyoxyethylene castor oil derivatives should be stored in a well-filled, airtight container, protected from light, in a cool, dry place.

Incompatibilities

In strongly acidic or alkaline solutions, the ester components of polyoxyethylene hydrogenated castor oil are liable to saponify. In aqueous solution, polyoxyl 35 castor oil (Cremophor EL and Cremophor ELP) is stable toward most electrolytes in the concentrations normally employed. However, it is incompatible

with mercuric chloride since precipitation occurs.

Some organic substances may cause precipitation at certain concentrations, especially compounds containing phenolic hydroxyl groups, e.g. phenol, resorcinol, and tannins.

Polyoxyl 40 hydrogenated castor oil (Cremophor RH 40) and polyoxyl 60 hydrogenated castor oil are largely unaffected by the salts that cause hardness in water. Cremophor RH 40 was found to prolong the dissolution time of digoxin tablets.(23)

Method of Manufacture

Polyoxyethylene castor oil derivatives are prepared by reacting varying amounts of ethylene oxide with either castor oil or hydrogenated castor oil under controlled conditions.

Polyoxyl 35 castor oil is produced in this way by reacting 1 mole of castor oil with 35–40 moles of ethylene oxide.

Polyoxyl 40 hydrogenated castor oil is produced by reacting 1 mole of hydrogenated castor oil with 40–45 moles of ethylene oxide. Polyoxyl 60 hydrogenated castor oil is similarly produced by reacting 1 mole of hydrogenated castor oil with 60 moles of ethylene oxide.

Safety

Polyoxyethylene castor oil derivatives are used in a variety of oral, topical, and parenteral pharmaceutical formulations.

Acute and chronic toxicity tests in animals have shown polyoxyethylene castor oil derivatives to be essentially nontoxic and nonirritant materials; see Table VI.(24,25) However, there are reports of cardiovascular changes and nephrotoxicity in various species of animals.(26) Several serious anaphylactic reactions,(27–38) cardiotoxicity,(39–41) nephrotoxicity,(42,43) neu- rotoxicity,(44) and pulmonary toxicty(45) have also been observed in humans and animals following parenteral admin- istration of formulations containing polyoxyethylene castor oil derivatives. The precise mechanism of the reaction is not known.

Table III: Typical physical properties of selected commercially available polyoxyethylene castor oil derivatives.

 

Name Acid value HLB value Hydroxyl value Iodine number Saponification value Water content (%) Melting point (8C) Solidification point (8C) Cloud point for a 1% aqueous solution (8C)    

Polyoxyl 35 castor oil (Cremophor EL) 42.0 12–14 65–78 25–35 65–70 2.80 19–20 — 72.5    

Poloxyl 35 castor oil, purified (Cremophor ELP) 42.0 12–14 65–78 25–35 65–70 40.5 — — —    

Polyoxyl 40 hydrogenated castor oil (Cremophor RH 40) 41.0 14–16 60–80 41 50–60 42.0 ≈30 20–28 95.6    

Polyoxyl 60 hydrogenated castor oil 41.0 15–17 50–70 41 40–50 42 ≈40 — —    

Etocas 29 — 11.7 — — — — — — —    

Etocas 35 — 12.7 — — — — — — —    

Etocas 40 — 13 — — — — — — —    

Croduret 7 Special — 4.9 — — — — — — —    

Croduret 40 — 13 — — — — — — —    

Croduret 50 Special — 14.1 — — — — — — —    

Croduret 60 — 14.7 — — — — — — —    

Eumulgin HRE 40 41.0 — 60–75 42 50–60 41.0 — — 76–82    

Eumulgin HRE 60 41.0 — 50–67 — 40–50 41 — <22 80–86    

Arlatone G Pharma — 10.8 — — — — ≈7 — —    

Cirrasol G-1284 — 13.1 — — — — — — —    

Hetoxide C5 — 4 — — — — — — —    

Hetoxide C-16 — 8.6 — — — — — — —    

Hetoxide C-25 — 10.8 — — — — — — —    

Hetoxide HC-16 — 8.6 — — — — — — —    

Hetoxide HC-40 — 13.1 — — — — — — —    

Hetoxide HC-60 — 14.8 — — — — — — —    

Jeechem CA-5 41.5 — 128–140 63–73 138–153 41.0 — — —    

Jeechem CA-15 41.0 — — — 95–100 41.0 — — —    

Jeechem CA-25 — — 75–85 — 77–85 41.0 — — —    

Jeechem CA-40 42.0 — 77–89 24–30 57–64 43.0 — — —    

Jeechem CA-60 42.0 — 42–55 — 28–38 412.0 — — —    

Jeechem CA-100 42.0 — — — 27–37 41.0 — — —    

Jeechem CA-200 42.0 — 20–34 — 14–20 41.0 125 — —    

Jeechem CAH-25 42.0 — 73–84 41.0 77–87 42.0 — — —    

Jeechem CAH-40 43.0 — 59–68 42.0 50–65 41.0 — — —    

Jeechem CAH-60 41.5 — 39–49 — 41–51 41.0 — — —    

Jeechem CAH-200 42.0 — 20–33 — 14–22 41.0 125 — —    

Lipocol HCO-40 43.0 — — 42.0 60–67 — — — —    

Lipocol LAV HCO-40 41.0 — 60–80 42.0 45–69 43.0 — — —    

Lipocol HCO-60 41.0 — 50–70 41.0 40–50 421.0 — — —    

Nikkol CO-3 — 3 — — — — — — —    

Nikkol CO-10 — 6.5 — — — — — — —    

Nikkol HCO-50 — 13.5 — — — — — — —    

Nikkol HCO-80 — 15 — — — — — — —    

Nikkol HCO-100 — 16.5 — — — — — — —  

Table IV: Typical physical properties of selected commercially available polyoxyethylene castor oil derivatives.

 

Name Density (g/cm3) pH Refractive index at 208C Surface tension of 0.1% w/v aqueous solution (mN/m) Viscosity at 258C (mPa s) Critical micelle concentration (%)    

Polyoxyl 35 castor oil 1.05–1.06 6–8 1.471 40.9 650–800 ≈0.009    

(Cremophor EL)    

Poloxyl 35 castor oil, purified 1.05–1.06 5–7 — — 600–750 ≈0.009    

(Cremophor ELP)

Polyoxyl 40 hydrogenated —

6–7

1.453–1.457

43.0

20–40(a)

0.039    

castor oil (Cremophor RH    

40)    

Polyoxyl 60 hydrogenated — 6–7 — — — —    

castor oil    

Eumulgin HRE 40 1.0220–1.0260 at 708C 6–7 — — — —    

Eumulgin HRE 60 1.0340–1.0380 at 708C 6–7 — — — —    

Arlacel 989 — — — — 1200 —    

Arlatone G Pharma ≈1.0 — — — ≈1400 —    

Cirrasol G-1284 ≈1.10 7–9 — — 1500 —    

Jeechem CA-5 1.0 6–8 — — — —    

Jeechem CA-9 1.02 5.5–7.5 — — — —    

Jeechem CA-15 1.021 6.0–7.5 — — — —    

Jeechem CA-25 1.04 6.0–7.5 — — — —    

Jeechem CA-30 1.01 6.5–7.5 — — — —    

Jeechem CA-40 1.1 5.0–8.0 — — — —    

Jeechem CA-60 1.068 5.0–7.0 — — — —    

Jeechem CA-100 — 5.5–7.0 — — — —    

Jeechem CA-200 1.08 5.0–7.0 — — — —    

Jeechem CAH-16 1.02 6.0–7.5 1.4665–1.4685 — — —    

Jeechem CAH-25 1.03 5.0–7.5 — — — —    

Jeechem CAH-40 1.1 5.5–7.5 — — — —    

Jeechem CAH-60 — 3.5–6.1 — — — —    

Jeechem CAH-100 1.1 3.5–6.1 — — — —    

Jeechem CAH-200 1.1 — — — — —    

Lipocol HCO-40 1.0 — — — — —    

Lipocol HCO-60 1.05 — — — — —  

(a) 30% w/v aqueous solution.

Table V: Solubility of selected commercially available polyoxyethylene castor oil derivatives.

Name Solubility

 

Castor oil Chloroform Ethanol Fatty acids Fatty alcohols Olive oil Mineral oil Water    

Polyoxyl 35 castor oil (Cremophor EL) S S S S S S — S    

Poloxyl 35 castor oil, purified (Cremophor ELP) S S S S S S — S    

Polyoxyl 40 hydrogenated castor oil (Cremophor RH 40) S S S S S S — S    

Polyoxyl 60 hydrogenated castor oil S — S(a) S S S — S    

Etocas 5 S — S — S — I I    

Etocas 29 S — S — S — I S    

Etocas 35 S — S — S — I S    

Etocas 40 S — S — PS — I S    

Croduret 7 Special S — PS — S — I I    

Croduret 40 D — S — D — I S    

Croduret 50 Special D — S — I — I S    

Croduret 60 D — S — D — I S    

Arlacet 989 — — S — — — — I    

Arlatone G Pharma — — S — — — I S    

Cirrasol G-1284 — — — — — — I D    

Jeechem CA-5 — — — — — — — D    

Jeechem CA-9 — — — — — — — D    

Jeechem CA-15 — — — — — — — PS    

Jeechem CA-25 — — — — — — — S    

Jeechem CA-30 — — — — — — — S    

Jeechem CA-40 — — — — — — — S    

Jeechem CA-60 — — — — — — — PS    

Jeechem CA-200 — — — — — — — S    

Jeechem CAH-16 — — — — — — — D    

Jeechem CAH-25 — — — — — — — D    

Jeechem CAH-40 — — — — — — — S    

Jeechem CAH-60 — — — — — — — S    

Jeechem CAH-100 — — — — — — — S    

Jeechem CAH-200 — — — — — — — S    

Lipocol LAV HCO-40 — — — — — — — S    

Lipocol HCO-40 — — — — — — — S    

Lipocol HCO-60 — — — — — — — S    

S = soluble, PS = partially soluble, I = insoluble, D = dispersible.    

(a) Need to add 0.5–1.0% water to maintain a clear solution.  

578 Polyoxyethylene Castor Oil Derivatives