Nonproprietary Names
Applications in Pharmaceutical Formulation or Technology
USP:Ascorbyl Palmitate Technology
PhEur:Ascorbyl Palmitate Ascorbyl palmitate is primarily used either alone or in combination USP-NF: Ascorbyl Palmitate with alpha tocopherol as a stabilizer for oils in oral pharmaceutical formulations and food products; generally 0.05% w/v is used. It may also be used in oral and topical preparations as an antioxidant
Synonyms
for drugs unstable to oxygen. The combination of ascorbyl L-Ascorbic acid 6-palmitate; ascorbylis palmitas; E304; 3-oxo-L- palmitate with alpha tocopherol shows marked synergism, which gulofuranolactone 6-palmitate; vitamin C palmitate. increases the effect of the components and allows the amount used to be reduced.
Chemical Name and CAS Registry Number
The solubility of ascorbyl palmitate in alcohol permits it to be L-Ascorbic acid 6-hexadecanoate [137-66-6] used in nonaqueous and aqueous systems and emulsions.
Empirical Formula and Molecular Weight
Description
C22H38O7 414.54 Ascorbyl palmitate is a practically odorless, white to yellowish powder.
Structural Formula
Table I: Pharmacopeial specifications for ascorbyl palmitate. Test PhEur 6.0 USP32–NF27 Identification Appearance of solution Melting range þ þ — þ — 107–1178C Specific rotation (10% w/v in methanol) þ218 to þ248 þ218 to þ248 Loss on drying 41.0% 42.0% Residue on ignition — 40.1% Sulfated ash 40.1% — Heavy metals 410 ppm 40.001% Assay (dried basis) 98.0–100.5% 95.0–100.5% 9 Pharmacopeial Specifications See Table I .
Functional Category
Antioxidant. 10 February 2009. 1100 1300 1500 1700 1900 2100 2300 2500 Wavelength/nm Figure 1: Near-infrared spectrum of ascorbyl palmitate measured by reflectance.
Typical Properties
NIR spectra see Figure 1. Solubility see Table II. Table II: Solubility of ascorbyl palmitate. Solvent Solubility at 208C unless otherwise stated(1) Acetone 1 in 15 Chloroform 1 in 3300 1 in 11 at 608C Cottonseed oil 1 in 1670 Ethanol 1 in 8 1 in 1.7 at 708C Ethanol (95%) 1 in 9.3 Ethanol (50%) 1 in 2500 Ether 1 in 132 Methanol 1 in 5.5 1 in 1.7 at 608C Olive oil 1 in 3300 Peanut oil 1 in 3300 Propan-2-ol 1 in 20 1 in 5 at 708C Sunflower oil 1 in 3300 Water Practically insoluble 1 in 500 at 708C 1 in 100 at 1008C
Stability and Storage Conditions
Ascorbyl palmitate is stable in the dry state, but is gradually oxidized and becomes discolored when exposed to light and high humidity. In an unopened container, stored in a cool place, it has a shelf life of at least 12 months. During processing, temperatures greater than 658C should be avoided. The bulk material should be stored in an airtight container at 8–158C, protected from light.
Incompatibilities
Incompatibilities are known with oxidizing agents; e.g. in solution oxidation is catalyzed by trace metal ions such as Cu2þ and Fe3þ.
Method of Manufacture
Ascorbyl palmitate is prepared synthetically by the reaction of ascorbic acid with sulfuric acid followed by reesterification with palmitic acid. Ascorbyl Palmitate
Safety
Ascorbyl palmitate is used in oral pharmaceutical formulations and food products, and is generally regarded as an essentially nontoxic and nonirritant material. The WHO has set an estimated acceptable daily intake for ascorbyl palmitate at up to 1.25mg/kg body- weight.(2) LD50 (mouse, oral): 25g/kg(3) LD50 (rat, oral): 10g/kg
Handling Precautions
Observe normal precautions appropriate to the circumstances and quantity of material handled. Ascorbyl palmitate dust may cause irritation to the eyes and respiratory tract. Eye protection is recommended.
Regulatory Status
GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Database (oral, rectal, topical preparations). Included in nonparenteral medicines licensed in the UK. 17 Related Substances Ascorbic acid; sodium ascorbate.
Comments
In order to maximize the stability and efficacy of ascorbyl palmitate the following precautions are recommended: stainless steel, enamel, or glass should be used; deaeration (vacuum) procedures and inert gas treatment are recommended where feasible; protect from light and radiant energy. The formation of ascorbyl palmitate vesicles (Aspasomes) and their pharmaceutical applications has been investigated.(4) The EINECS number for ascorbyl palmitate is 205-305-4. The PubChem Compound ID (CID) for ascorbyl palmitate is 5282566. 19 Specific References 1 Kla¨ui H. Tocopherol, carotene and ascorbyl palmitate. Int Flavours Food Addit 1976; 7(4): 165–172. 2 FAO/WHO. Toxicological evaluation of certain food additives with a review of general principles and of specifications. Seventeenth report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1974; No. 539. 3 Sweet DV, ed. Registry of Toxic Effects of Chemical Substances. Cincinnati: US Department of Health, 1987. 4 Gopinath D et al. Ascorbyl palmitate vesicles (Aspasomes): formation, characterization and applications. Int J Pharm 2004; 271: 95–113.
General References
Austria R et al. Stability of vitamin C derivatives in solution and topical formulations. J Pharm Biomed Anal 1997; 15: 795–801. Daniel JW. Metabolic aspects of antioxidants and preservatives. Xenobiotica 1986; 16(10–11): 1073–1078. Pongracz G. Antioxidant mixtures for use in food. Int J Vitam Nutr Res 1973; 43: 517–525. Sˇpiclin P et al. Stability of ascorbyl palmitate in topical microemulsions. Int J Pharm 2001; 222: 271–279. Weller PJ et al. Stability of a novel dithranol ointment formulation, containing ascorbyl palmitate as an anti-oxidant. J Clin Pharm Ther 1990; 15: 419–423.
Author
PJ Weller.
Date of Revision
9 January 2009.