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01 Excipients Prelims 1..9

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01 Excipients Prelims 1..9 Calcium Stearate 1 Nonproprietary Names 9 Pharmacopeial Specifications C BP: Calcium Stearate See Table I. JP: Calcium Stearate PhEur: Calcium Stearate 10 Typical Properties USP-NF: Calcium Stearate Acid value 191–203 Ash 2 Synonyms 9.9–10.3%; Calcii stearas; calcium distearate; calcium octadecanoate; Deasit 9.2% for Synpro. PC; HyQual; Kemistab EC-F; octadecanoic acid, calcium salt; Chloride <200 ppm stearic acid, calcium salt; Synpro. Density (bulk and tapped) see Table II. 3 Chemical Name and CAS Registry Number Octadecanoic acid calcium salt [1592-23-0] SEM 1: Excipient: calcium stearate (standard); manufacturer: Durham Chemicals; lot no.: 0364; voltage: 20 kV. 4 Empirical Formula and Molecular Weight C36H70CaO4 607.03 (for pure material) The USP32–NF27 describes calcium stearate as a compound of calcium with a mixture of solid organic acids obtained from fats, and consists chiefly of variable proportions of calcium stearate and calcium palmitate. It contains the equivalent of 9.0–10.5% of calcium oxide. The PhEur 6.3 describes calcium stearate as a mixture of calcium salts of different fatty acids consisting mainly of stearic acid [(C17H35COO)2Ca] and palmitic acid [(C15H31COO)2Ca] with minor proportions of other fatty acids. It contains the equivalent of 9.0–10.5% of calcium oxide. 5 Structural Formula SEM 2: Excipient: calcium stearate (precipitated); manufacturer: Witco Corporation; lot no.: 0438; voltage: 12 kV. 6 Functional Category Tablet and capsule lubricant. 7 Applications in Pharmaceutical Formulation or Technology Calcium stearate is primarily used in pharmaceutical formulations as a lubricant in tablet and capsule manufacture at concentrations up to 1.0% w/w. Although it has good antiadherent and lubricant properties, calcium stearate has poor glidant properties. Calcium stearate is also employed as an emulsifier, stabilizing agent, and suspending agent, and is also used in cosmetics and food products. 8 Description Calcium stearate occurs as a fine, white to yellowish-white, bulky powder having a slight, characteristic odor. It is unctuous and free from grittiness. 103 104 Calcium Stearate SEM 3: Excipient: calcium stearate (fused); manufacturer: Witco 2.0 2326 0.3 Corporation; voltage: 15 kV. 2295 1748 2339 0.0 1215 1765 C 2440 1731 2388 log(1/R) 2352 [2nd deriv. log(1/R)] × 2312 1000 −4.0 −0.2 1100 1300 15001700 1900 2100 2300 2500 Wavelength/nm Figure 1: Near-infrared spectrum of calcium stearate measured by reflectance. Table II: Density (bulk and tapped) of calcium stearate. Bulk density (g/cm3) Tapped density (g/cm3) Durham Chemicals Standard — 0.26 A — 0.45 Table I: Pharmacopeial specifications for calcium stearate. AM — 0.33 Ferro Corporation Test JP XV PhEur 6.0 USP32–NF27 Synpro 0.2 — Witco Corporation þþþ Identification EA 0.21 0.27 Characters þþ— 3 Fused 0.38 0.48 Microbial limit — 10 cfu/g — Precipitated 0.16 0.20 þ Acidity or alkalinity — — Undesa 4 4 4 Loss on drying 4.0% 6.0% 4.0% Kemistab EC-F 0.3 — Arsenic 42 ppm — — Heavy metals 420 ppm — 410 mg/g Chlorides — 40.1% — 2 4 Specific surface area 4.73–8.03 m /g Sulfates — 0.3% — Sulfate <0.25% Cadmium — 43 ppm — Lead — 410 ppm — Nickel — 45 ppm — 11 Stability and Storage Conditions Assay (as CaO) — — 9.0–10.5% Calcium stearate is stable and should be stored in a well-closed Assay (as Ca) 6.4–7.1% 6.4–7.4% — container in a cool, dry place. 12 Incompatibilities Density (true) — 1.064–1.096 g/cm3; 1.03 g/cm3 for Kemistab EC-F. 13 Method of Manufacture Flowability 21.2–22.6% (Carr compressibility index) Calcium stearate is prepared by the reaction of calcium chloride Free fatty acid with a mixture of the sodium salts of stearic and palmitic acids. The 0.3–0.5%; calcium stearate formed is collected and washed with water to 0.3% for Synpro. remove any sodium chloride. Melting point 149–1608C; 14 Safety 130–1568C for Kemistab EC-F; Calcium stearate is used in oral pharmaceutical formulations and is 1558C for Synpro. generally regarded as a relatively nontoxic and nonirritant material. Moisture content 2.96%; 15 Handling Precautions 2.7% for Synpro. Observe normal precautions appropriate to the circumstances and NIR spectra see Figure 1. quantity of material handled. Calcium stearate should be used in a m m Particle size distribution 1.7–60 m; 100% through a 73.7 m well-ventilated environment; eye protection, gloves, and a respira- m (#200 mesh); 99.5% through a 44.5 m (#325 mesh). tor are recommended. Shear strength 14.71 MPa Solubility Practically insoluble or insoluble in ethanol (95%), ether, chloroform, acetone, and water. Slightly soluble in hot 16 Regulatory Status alcohol, and hot vegetable and mineral oils. Soluble in hot GRAS listed. Included in the FDA Inactive Ingredients Database pyridine. (oral capsules and tablets). Included in nonparenteral medicines Calcium Sulfate 105 licensed in the UK. Included in the Canadian List of Acceptable 19 Specific References Non-medicinal Ingredients. 1 SpecialChem (2005). Metallic stearates center. http://www.special- chem4polymers.com/tc/metallic-stearates/index.aspx?id-2404 17 Related Substances (accessed 13 February 2009). Magnesium stearate; stearic acid; zinc stearate. 2QiXLet al. Preparation of tablets containing enteric-coated diclofenac sodium pellets. Yao Xue Xue Bao 2008; 43(1): 97–101. 3 El-Kamel AH. Testosterone solid lipid microparticles for transdermal C 18 Comments drug delivery. Formulation and physicochemical characterization. J Calcium stearate exhibits interesting properties when heated: Microencapsul 2007; 24(5): 457–475. softening between 120–1308C, and exhibiting a viscous consistency 4 Food Chemicals Codex, 6th edn. Bethesda, MD: United States at approximately 1608C. At approximately 1008C, it loses about Pharmacopeia, 2008; 151. 3% of its weight, corresponding to 1 mole of water of crystal- lization. The crystalline structure changes at this point, leading to the collapse of the crystal lattice at a temperature of about 1258C.(1) 20 General References Calcium stearate was studied as a component of a ‘cushioning Bu¨ sch G, Neuwald F. [Metallic soaps as water-in-oil emulsifiers.] J Soc pellet’ during compression of enteric-coated pellets to protect the Cosmet Chem 1973; 24: 763–769[in German]. enteric coating. The cushioning pellets were composed of stearic Phadke DS, Sack MJ. Evaluation of batch-to-batch and manufacturer-to- acid/microcrystalline cellulose (4 : 1 w/w) and were successful in manufacturer variability in the physical and lubricant properties of avoiding rupture of the enteric coating during the compression calcium stearate. Pharm Technol 1996; 20(Mar): 126–140. process.(2) Calcium stearate was hot-melt extruded with testosterone in a study to characterize testosterone solid lipid microparticles to be applied as a transdermal delivery system. The results showed good 21 Author release of the drug from the matrix.(3) See Magnesium stearate for further information and references. LV Allen, Jr. A specification for calcium stearate is contained in the Food Chemicals Codex (FCC).(4) The EINECS number for calcium stearate is 216-472-8. The 22 Date of Revision PubChem Compound ID (CID) for calcium stearate is 15324. 13 February 2009. Calcium Sulfate 1 Nonproprietary Names 6 Functional Category BP: Calcium Sulphate Dihydrate Desiccant; tablet and capsule diluent. PhEur: Calcium Sulphate Dihydrate USP-NF: Calcium Sulfate 7 Applications in Pharmaceutical Formulation or Technology 2 Synonyms Calcium sulfate dihydrate is used in the formulation of tablets and capsules. In granular form it has good compaction properties and Calcium sulfate anhydrous anhydrite; anhydrous gypsum; anhy- moderate disintegration properties.(1,2) drous sulfate of lime; Destab; Drierite; E516; karstenite; Calcium sulfate hemihydrate (see Section 17), is used in the muriacite; Snow White. preparation of plaster of Paris bandage, which is used for the Calcium sulfate dihydrate alabaster; calcii sulfas dihydricus; Cal- immobilization of limbs and fractures; it should not be used in the Tab; Compactrol; Destab; E516; gypsum; light spar; mineral formulation of tablets or capsules. white; native calcium sulfate; precipitated calcium sulfate; Anhydrous calcium sulfate is hygroscopic and is used as a satinite; satin spar; selenite; terra alba; USG Terra Alba. desiccant. The uptake of water can cause the tablets to become very hard and to fail to disintegrate on storage. Therefore, anhydrous 3 Chemical Name and CAS Registry Number calcium sulfate is not recommended for the formulation of tablets, capsules, or powders for oral administration. Calcium sulfate [7778-18-9] Therapeutically, calcium sulfate is used in dental and craniofacial Calcium sulfate dihydrate [10101-41-4] surgical procedures.(3,4) 4 Empirical Formula and Molecular Weight 8 Description CaSO4 136.14 Both calcium sulfate and calcium sulfate dihydrate are white or off- Á CaSO4 2H2O 172.17 white, fine, odorless, and tasteless powder or granules. 5 Structural Formula 9 Pharmacopeial Specifications See Section 4. See Table I..
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