Ie has been shown that the increased force required to expel coconut oil fam plastic syringes was due to uptale ofthe ol ino the rubber plunger; this resulted in swelling ofthe rubber plunger and ap) inereased” resistance to movement down the ‘sycinge wee aa 13 Method of Manufacture Coconve oil is the fixed oil obrained from the seeds of Cocos nucifera Lin. (Paltmae). This oils then refined to produce refined coconut oil, whichis referred 1o in the coconut industry as RED, (refined, bleached, and deodorized) coconut cil 14 Sofety When adminiscered orally, coconuc oil is essentially nontoxic, slthough ingestion of large amounts. omay cause digestive oF fastroincesdnal ivtation oF upsee. Coconuc il can act as aa estat when applied tothe skin and when im cantace with the eyes yy be absorbed through the skin. lobilation of mist oF vapor may cause respiratory tract eta 15. Handling Precautions Observe normal precautions appropriate to the circumstances and. quantity of the aerial handled. Coconn¢ ol should be kept away fom heat and sources of ignition, and contact with oxidizing agents, acid, and alkalis showld be avoided Tei the solid form, lage spillages of cocanut oil shoul be deale with by shoveling che material into. svaste disposal container, For liquid Spillages, the ei shuld be absorled with an inest material betore removal for €isposa 18 Regulatory Status Included in che FDA Inactive Ingeedients Database (ora canst and tablets topical creams, solutions, aad on Scalp intents and therapeutic shampoos licensed 17 Related Substances Almond el; anol oil castor ol; castor oil, hydeoxenateds corn coitonseed ik, mediumehain triglycerides; olive oil; peanut cil Sesame oi; soybean cil, sunflower ol. {> Colloidal Silicon Dioxide 1 Nonproprictary Nemes DP. Cola Anyous in igh aby Sce Ad Pir Sicn, Caos Ayous USPINP, Cail Sicon Diode 2 Synonyms LL Avrosi; Cab-OSil: Cab-O-Si! MSP; colloidal silica: fumed silica, famed silicon dioxide; hochdspersessilicum dionidy $43) silica collotdalis anhydeea; silica sol; silicic anhydride; sien dioxide colloidal; silicon dioxide fumed; syntheric amorphes silica Wacker HDK 1 Colloidal Silicon Dioxide 185 18 Comments A specification for coconut oil (aphyydeogenated) is contained ithe Food Chemicals Codex {FOC}. 19° Specific References 1) Hang CE etal The eer of oi components on the physcochemal propectis abd deug delivery of emelstone tocol exalsion vers lipid son IJ Pho 2007, 9361-2. 193-202, Akad O. Preparation of cloudy coconut oil emulsions tg dispersed THO using atonzes J Dispersion Se) Tb 1986, 75 S153, 3 Fang et Lipid uanohubmiccon emails 8 every vehi or ‘opie fariprofn delivery, Orig Des 2004, 192} 97-105, 4 Neen TW" er al. Tneanasaladminitncion of lee liquid formuloions of buseanide to rabbit. bu J Pharm 2000; 20611"2) ae 5 Tanabe K ot al. Eifece of diteren supposcory bases on release of indomethacin J Pharm Se ecb Jom 1084, 4; 115°120, 6 BrodaHaral Pepacation and esting of suppositories with cepheadie ~ evaluation of phaunaceuteal avaabity and blegcal ara. urn Pol 1993; 4911 o1 2h 8, 7 Osbols DO et an wir antimicrobial properties of of coconat ol on (Civ species ia fbadan, Nigeria. J Med Food 2007, 102). 384-387, nso. Niion, Parr) 2000, 265.45. Pajoubuand A eral Survival Galowing sevetealusiniany phosphide poston, Phorn Proce Res 003,334) 397-299. 10 Patel TR Sales of coconut. Pann} 1992; 249.382 Ui Todd 8G, Wade, es. The Pbarmtcetical Codex, Lhe, Landon Dhoreacarcl Ores, 1979, 211 12 Desir Bis hott Mf The evaloaion ofthe orceta expel injection ‘chiles fom syringes, J Pharm Pharnzeol 1979 3197-800, 13 Food Chemicals Coles, th edn.” Detesda, MD: Unied Sats Phanoasopic, 2008, 233, General References 22 Date of Revision 27 February 2009, 3 Chemical Name and CAS Registry Number Silica (7631-86-5] 4 Empirical Formula and Molecular Weight SiO, 60.08 5 Structural Formula See Section 4. 6 Functional Category Adsorbent;antcaking agent; emulsion stabilize; glidant suspend- inggagentstablee disintegrant; thermal stabilizer; viscosity increasing agent186 Calleidol Silicon Dioxide 7 Applications in Pharmaceutical Formulation or Technology Colloidal silicon dioxide is widely sed ia pharmaceuscals onesies, and Food products; se Table 1 ts small parle ie and Targe sexi surface acca give ie dsieabe low charactsistis that ae eapowed to improve the flow neopets of dry powders ina numberof process such as tablet an expe fling. Colloidal siicon dioxide i also used to stabilize emulsions and as a thootopic thickening and suspending agent in gels and Semisoidprepacations." With other ingredients of snl rele tive index eraparet gels may be formed The degree of wscosty increase depends on the polarity of she lguid polar liguids ienerally eure a reste concentration of colloidal ticon dene than nonpolar guid). Viscosy is largely independent. of temperatre: However, changes tothe plT ofa syste may at the escosig see Section 11 In aerosols other than those for inbalation, colloidal silicon diosie is wed to promote particulate suspension, eliminate asd seuling, and. minimize the clogging of spray novles. Colla) Silcon iexide is also used aya tabler Uismeegrane ands. an adsorbent dispersing agent for liquids in povakcrs Collokdal Sicon diowde i tequendy added to suppository formulations conaining lpophile excipients to erease viscosity, prevent Sedimentation daring molding, and decrease the release rate Colloalsicon dose is also usa 9¢ an adsorbent during the Preptation of wax microsphere” au a thickening. agen for topical preparacons; and as heen sede) aid the Ieeze-deying of nanoeapsules and nanosphere suspensions." Tobe t Uso of cllidl sheen donde, Ue Concenirtion Aecaks 05-20 Emon sobiize 1050 ait9, 20-100 8 Description Calloida! silicon dioxide is a submicroscopic fumed silicn with 2 parce size of about 15 nm leis alight, loos, bluish-white-colored, dors, asteless, amorphous powder SSE Espen! cll sileon dose [Aeros A200); monufacre: Evonk Dogusse Corp tno: B72 [O419C), magnieaian: 00>, ‘olage: 20k 58! Excpiont:clledal slicon diode (Neos A200}; manfocirer Evonik Dagusto Carp. hana: 87% (04169C}; mogniicton: 2.400% vahage: 2080. 9 Pharmacopeial Specifications ‘See Table I. See alka Section 18, Table i Phomocopaialseciicaions fr tolidllcondibide Tot JeXY Pwr. USPS2-NFZT ifentiesion + . Chorastre . £ S BALE w/e depersion) = 3555 3555 Avonie Seem 8u/ hove 0.011% — &250ppm Heavy metas SA0pem £25 ppm ‘Abana : Cole + how 500pom 2 less on dying <70% 25% lesson igtian E1204 sou 20% ‘lone eg won}. 270m = = Asay (on gnied sample] 298.0% —_99.0-100.5% 990-100.5% 10. Typical Propertios Aciditylalkalinity pki =3.8-4.2 (4% wi aqueous dispersion) an 3.5-4.0 (10% wiv aqueous dispersion) for Cab-O-8il MSP Density (bulk) 0.029-0.042 pers Dousity (tapped) see Vables Ill, TV, and V. Melting pornt 1600°C. Moisture content sce Figare 1.02" Particle sive disvilution » Primary particle sizes 7160, Aeroit forins loose agglomerates of 10-200 im. See alo Figuce 2 Refractive index 1.46 Solubility Practically insoluble in onganie solvents, water, and ‘acids, except hylrofluecic acid; soluble in hor solutions of alkali hydroxide, Forms a colloidal dispersion with watec For Aerosi, solability i water is 150mg/L at 25°C (pH 7) Specific gravity 2.2 Specific Surface area 100-400 aig depending on grade, See also Tables I (Vand V. Several grades of colloidal silicon dioxide are commercially available, wlich are produced by modifying the manufactue ing process. The modifications da not affect the silica content,89, 70 oo sof 4 30 Equilibrium maisture (%) 20 10 °o 10 20 30 40 30 60-70 80 90 100 Relative humidity (%) + Serlon-desorpion them fo coloidel sikcon diode 100 90] 20] 70| | 30 «0 50 Weight oversize (%) 20 tof °o 10 20-30 40 30 60 70 ad $0 100 Particle size (pm) Sigur 2 Reticle size dstibtion of eolidlsticon dioxide [Aeros 4 200, Evenik Degussa Comp) specfe gravy, retrace inden colon or amorphous frm However pale size, surface areas and. desc ate alfeaed, "The physical properties of thee conmerialy Srailable aod siicon diodes, Acroa! von Degussa. Gorm), Cab-0.S (Calor Corporaony and Wacker HDR (WackeeChemie GB) are spown in Tales Ul, TV and ¥, respec 11. Stability and Storage Conditions Colloidal silicon dioxide is hygroscopie buc adsorbs large quanciies, fof water without lquefying, Wen weed in aqueous system ata pH 0-75, colloidal silicon dioxide is elective in snereasing the viscosity of « System. However, at a pH greater chan 7.5 the viscosity Increasing properties of colloidal silicon dioxide ave reduced and at 2 pHl greater shan 10.7 this ahility is lost eniely since the scom Uiexide dissolves co form silicates." Colloidal silicon dioxide powder should be stored in a well-closed eoneaines, Colloidal Silicon Dioxide 187 Tobe Mk Physical prepenies of Aci ea Grade Spacticsufoce ere Deny topped) i/o?) nial a 130 1304.28 05 130. 130.5 25 O12 200 200 38 05 200+ 2003 23 012 300) 500 £30, bas 500 500 £30, 012 30 380.830 05 38038030 one (0B Toble ve Physical propmies of CabOSt io Grade Specie surface creo" Density oppe en? inva) ™ ow as 130 4 25 50 130.2 28 ms 200228 Hs jas 28 es 390 2 40 ra 203 . (lee eto Table Vi Physical properties WackorHOK, Grade feces ac Doty tre fen’) inl 2 213 125 « 15 208 vis 0.08 Noo doe 0 doe 140 Boe ed Sou 0 Soa #30 808 3000 032 Hobe 8.08 Hoo1s 0 020 12050 10830 020, - (8 a 12. Incompatibilities Incompatible with diethyltilbestrol preparations.) 13. Method of Manufacture Colloidal silicon dioxide is prepared by the flame hydrolysis of cblocosilancs, such as silicon tetrachloride, at 800°C using, @ hydroger-oxygen flame. Rapid cooling from the molten state ‘during manufacture causes the product to remain amorphos. 14 Sefety Colloidal siicon dioxide is widely used in oval and topical ppharmaceorical products nd is generally regarded as an essentially nontoxic and noniretant excipient. However intraperioneal and subcutaneous injection may produce local dssue reactions andor walomas, Colloidal silicon dioxide should therefore not be istered parenterally. Ds (eat, IV} 0.015 ge!" LDsy (t86 oral} 3.16 kg Be a188 Colloidal Silicon Dioxide 15. Handling Precautions Observe normal precautions appropriate to the circumstances and quantiy of material bandied. Eye protection and gloves are recommended. Considered a nuisance dust, precautions shoul be ‘taken avoid inhalation of colloidal silicon dioxide, ln the absence ‘of suitable containment facies, dust mask shonid he worn when handling small quantities of material. Por larger quanites,a dust respicator is recommended. Inhalation of colloidal silicon dioxide cust may eause irritation to the respiratory act but its not associated with fibrosis of the Fungs(iitosis) which ean oecur upon exposure to crystalline silica, 16 Regulatory Acceptance: GRAS listed. included in the EDA Inactive Ingredients Database (oral capsules, suspensions, and cable; teansdermal, eectal, and ‘vaginal preparations) Also approved by the FDA asa food adaive and for food contact, Inchaded in noaparenteral medicines licensed jn the UK. Included in the Canadian List of Acceptable Now ‘medicinal Ingredients. 17 Related Substances Hydrophobic colloidal sila, 18 Comments Colloidal silicon dioxide is one of the materials that have been selected for harmonization by the Pharmacopeial. Discussion Group. For further information see the General Information Chapter <1196> in the USP32-NF27, the General Chapter 5.3 ju PHEue 6.0, along with the State of Work’ document on the PhEur EDQM website, and also the General Information Chapter 8in the BPX, The PhEur 6.0 also contains « spevification for hydrated colloidal silicon dioxide. ‘The incidence of microbial contamination ‘of colloidal silicon dioxide is low!" de co the high production temperatures and inorganie precursor materials ‘Note that porons silica el particles may also be vscd as a aidan, thickener, dispersant and to adsorb moisture which maybe an advantage for some formalations. Syoid 2447? mects the USP= INP requirements Jor silicon dioxide, and Syloid 244 FP-BU meets the PhEur and JP requicements for silicon diowide,"" Another CAS number that is used for colloidal silicon dioxide is 112345.52.5 The EINECS number for colloidal silicon dioxide is 231-545-4 ‘The PubChem Compound ID {CID} for colloidal silicon dioxide 24261. 19. Specific References 1 York B Application of powder fale testing equipment in assesing fie of dans on Sowabality of ehesie pharaacuticl pov. J Phanne 31975, 68; 1216-1221 Lee CF ef of interact of lubricants and colloidal ice ding ‘mixing with excipients effec on tabesting, Pharm Ata Hb 197% ase. 3 Lark GE Rolmis GK, Inversion of lobicans and colloidal sia using xing with excipins Telecom wettability ad olin velocity, Pharm Acta Hele 1977; 82: 39-44 4 Joust at al Taiacne of compacted byéoopbobie and hydeophie colloidal sicon dioxide on tblesing properties of pharmacciticl ‘cpins: Drug De Ind Phar 248; 31 687-496, 5, Daniels eral The sabi of dug absortates om silica. Drug Dee Ind Pharm 1986; 13: 2127-2156 6 Shavit M, Ease RP Rbeologeal aud de eleaseprepetcs of ol fel soncaning olla slcon digs, J Pharm Si 197% 6H B42 7 Toker |}, De Racy CJ. The scion of calla silicon dioxide to stupension suprontorcs le The impact on i aro rleae ad oneal. Arto Pane Technol 1984, 30: 135-160. 8 Reakdon Nata. fers of silcum dioxide om davg clase fom ‘suppositories: rug Dex Ind Phare 199723. 1025-1001 9 Mani Net al Microencapsulstion of & hudrophiie drug ino a Hdrophobic murs sh a salngove procalue, fl Ete of useuent on’ mieosphere prnpentis. Drag Dev bed Phar 20, SOU: 5-95, 10 Gallagher 5) ral. Etfcets of membrane ype and Kgudiqu phase boundary on ro selese of ketopefer ony pel formations J Drag Target 2003; 316} 373-379, 1 Schaitanc SR otal, Frese dying polymeric cllidalsbspensions ‘anocapls, ntncnpheres and hangers, A compare std Eur Phone Biopharm 2008; S63) 301-308 12 Entinger Mf a [Adtorpion ar eve sac of fred lien.) Arch Pharm 1947 320, |=IShin Cerna 13, Callan JC ef ak Eqasbeum moisture content of pharnceatical ‘cpients. Ding De Ind Phan 1982, 3550369, 14 Cabot Corporanon Tele Irate: Cabs OS fumed sie he Peformance adives, 1995 15. Johansen I, Mller Ni. Solve deposion of deupe on excpions inveepresion oils, sorpcion and abeoreion charac sts ‘of dge Arch Pharm Chen Sl Ed 19775: 33-1, 16 Lewis ed Soe Dangers Properties of dual Mater eh fd New York Wiley, 004; 3208, 17 Rienbols M. [he behavivut of bacera in highly pre slice acid Pharm Id 19 32: 677-6790 Gers 18 WH Grace & Co. Techni liner: Splnid 244, 2002, 20 General References ‘Cabot Corporation. echnical ieeatute PDSI7: Gab-O Si M50 2006, Evonk Degussa Coes. Teal Bullen Fine Parles Now 11 TOOT "asc charscterac Aeros red sil 2006 Evonik Degussa Corp. Tehmcal Meratere 11 128)-t» Aeros colloidal “icon desi fr phaemacetia, 2006 Europens Diesorae for the Qualisy of Madicites and Healdare [EDQM). European Phaenacopeca ~ State OF Woke Ot inernationa| Harmonisision. Phurnentopa 2009; 211 42-143, heparan smceubiel or 4hea sccessed 3 February 2009), Moree K. Zimermunn 1 Ect uf gant binaey powder mixtures. ower Technol 2004, 139. 40-54, ‘Wacker Chemie Gl. Toshnial liesaure: Wacker FIDK ued sen, 1998 Waddell WW. Sica amorpliaus Kak Orbner Enovclapedia of Chemeal Technology Sth in, vol. 22: New York Johs Wiley 8 Sons, 2001, s80i0e ‘Wagner Brunner. Aerie its peeparation, popes and behaioa i ‘nga bau. Angee Chon 1980, 72: 734-750, Yang KY er a lec of acrbous sion diosices on drug dslution | ‘Pharm Se) 1979; 38: 560-365. ‘inestna Jet el. Nanomaterials a8 flow eeglstors in dey powders. Z Phys Chem 2004 218: 51-102 21 Author KP Hapgood. 22 Date of Revision 3 February 2008