sisii2 Nousiin - Application Data English sees Neusilin CATEGORIES Pharmaceutical Application Dils and extracts to powder Improve flow Anti caking Compressibility Solid dispersion Hygroscopic velocity curve of Neusilin® Hygroscopic equilibrium curve of Neusilin® Cosmetic Application eee meer errr rere eeee References Application Data Typical Application and Quantity Needed in Pharmaceutical Preparationsi512 Nousiin - Application Data a a... .6- aneennen st ae ota! SSS ee erm = = | = |= =) = | 5070 esters) eee Anca Peres = = |) |= = 4) | aos5 cry Pharmaceutical Application I. Oils and extracts to powder 1Ns2N 30:90 1.40 140 055 055 15. 515 30:90 140 eoty ‘The most suitable grade for converting oil to powder is Neusitin® US2. When the oil ad is comparatively high, an addition of 0.5 to 2% UFL2 will improve flowabilty substantially. Newsiin® UFL2 alone at 0.5% can resolve sticking issues of oily formulations. Schematic flow 6:66:60 Oil adsorption capacity ve st FH2 —-US2 —-UFL2-—« MCC. Colloidal silica Neusilin® US2 and UFL2 grades show highersisii2 Nousiin - Application Data Oil to Powder Free flowing powder of linseed oil (with Neusilin® US2) f 281 Neusilin® US2 + 30% linseed oil, Dry at 50’ Linseed oil tablet, @ 1.3mm, 125N at $00kg/em? Tablets of Scopolia extract and soybean oil (with Neusilin UFL2) 10 Monsanto Hardness (ka/em?) Scopolia extract powder Soy bean lecithin powder o 500 1,000 1,500) 2,000 Compression pressure (kg/em?) A mixture containing 25% Scopolia tt Sb il d25%UFL2 dd ith 1 tfLt Thi itsisii2 Nousiin - Application Data Tablets of Vitamin E (with Neusilin® US2) 400 VE 20%, US2 76% VE 25%, US2 71% 350 VE 30%, US2 66% VE 40%, US2 56% 300) -) 4 ve sox, us2 46% 250} use 100% 2 20 I 5 150 100 50 250 500 750 ‘Compression pressure (Ke/om) An ethanol solution of tocopherol acetate (VE) 20-50% was compounded with proportional amount of Neusiin® and mixed well. ‘To this mixture, 3% Croscarmellose sodium and 1% Magensium stearate was added before tabletting. High quality tablets with a load of up to 30% Vitamin E can be prepared with Neusilin® US2. Back to top IL. Improve flow Angle of repose after adding excipient to potato starch 70 Colloidal silica Calcium silicate 60 Neusiling® UFL2 Angie of repose 0 02 OF 10 15s 20 30 40 Concentration (%) ‘Neusilin® UFL2 particle stick to the surface and aid flowsisii2 Nousiin - Application Data Potato starch. (x1,000) Potato starch (10,000) Potato starch + Neusilin® Potato starch + Neusilin® (x 10,000) Electron micrograph showing Neusilin® UFL2 partick UFL2 particles stick to the surface and facilitate flow icking to the starch surface. On addition to starch, the ina ‘roller blade’ model A 0 5% addition of UFL2 tosisii2 Nousiin - Application Data II. Anti caking Addition of 0.5% Neusilin® UFL2 prevents caking 35 30 @— Lactose Mec o— Potato Starch 25 Min Dia of erfce of low (mm) 0 1 2 3 ‘Amount of Neusilin® UFL2 added (%) ‘Neusilin® UFL2 prevents caking at high humidity conditions Sodium L-aspartate at 45°C, 75% RH, 2 days Sodium L-aspartate with 0.5% UFL2 at 45°C, 75% RH, 2 days Back to top Vc ibilitsisii2 Nousiin - Application Data ‘Neusilin® UFL2 increases lactose tablet hardness . 140 “@— 10% Neusilin® UFL2 Y v0 Se Nesting UFL2 “ = 60 Ae © ¢ » 0 500 1,000 1,500 ~—2000 2,600 Compression pressure (kgfem®) Compounding Lactose with 10% Neusiin®® UFL2 results in higher hardness when compared to 15% microcrystalline cellulose, Neusiin® US2 at similar levels can also be used to improve hardness of tablets, High quality tablets at low compression pressure 200 180 = - 100 Hardness (N) 50 1,000 1,500) 2,000 Compression pressure (kgm) Comstareh + Lactose Comstaren + Lactose + NeuslinUS2 5% Comstaeh + Lactase + NeusiinBUS2 10% —e— Cornstarch + Lactose + Colloidal silica 10% Comstaeh + Lactose + Calida sca 15% 4 — Cornstarch + Lactose + Caleium siete 5% Gomstarch + Lactose + Caleium siicate 10% Tablet hardness of comstarch/lactose based tablets compounded with either using Neusiiin® US2 colloidal silica or calcium silicate Com starchsisii2 Nousiin - Application Data Back to top V. Solid dispersion Formulating poorly water soluble drugs by solid dispersion leads to a remarkable improvement in dissolution and bioavailability. Neusilin® can potentially resolve problems associated with tabletting and improve efficiency of solid dispersion, Three methods to apply adsorbent carriers in different solid dispersions Hot Melt Solvent adsorption Emulsion system Poorly soluble API Poorly soluble API Poorly soluble API Polymers or Surfactants 0 suractants/eo ‘or mixture of both Carrier surfactants Polymers or Surfactants Carrier Or mixture of bath a Soli dispersions Soli alspersions SMEDDS/SEDDS ‘Tablets or Capsules Tublets or Capsules Tablets or Capsules V@). Key advantages of Neusilin® as an adsorbant Improve flow High quality tablets at low compression forces High specific surface area High adsorption capacity Higher API load Restricts reversion of amorphous form to crystalline state Inert core material eee wees Vii). Solid dispersion Published examples In developing a solid dispersion system for the BAY 12-9566, Gupta et al,1,2 prepared temary dispersion granules using hot-melt granulation, First, the candidate drug BAY 12-9566 was added to a molten solid dispersion carrier, Gelucire® 50/13 maintaining a temperature of 90°C. Neusilin® US2 was preheated to 80°C ina granukator for 15 min with sting at 300 rpm. The molten mixture was then added drop-wise over a period of one minute to Neusilin® with continued stirring. Hot melt granulation was performed at an increased stirring speed of 600 rpm for one more minute to obtain ternary dispersion granuks of drug, Gelucire® 50/13 and ‘Neusilin® US2. The dispersion granules were allowed to come to room temperature by air cooling followed byaisi2 Neustin-Aptcaton Data 1) Gupta et al, Pharm Dev Tech, 6: 563- 72, 2001 2) Gupta et al, Pharmaceutical Research, 19:1663-72, 2002 Poorly water Molten dispersion Adsorbent soluble drugs carriers BAY-12-9566 Naproxen (Soluce 50/13 Neusiine us2 1 Ketopoen or Hot matt rdomethacin EG 8000 Grandlaton Testosterone 5 Phenacetn 7. Progesterone 250 a vital 200 i ME 2 weeks “4 weeks 180 100 50 : : 8 3 j g KaYGIN. BayGIN BayPIN NapGIN Nap/PIN Ind PhelGN TexGIN PRIGIN Pron Net Yotopefen he: Phenacin —_—G: Glucke ay: BAYI2-9565 Ter: Teotrne PEG 6000 Nop: Nepeoen Pr: Progestercne In Indomethacin N: Nestle Comparison of drug dissolution (after 30 min) fiom intial and stored solid-dispersion granules using USP Type II apparatus at 50 rpm. Data are shown for drug dissolution (% of intial) from solid-dispersion granules after storage at 40°c/75% RH (Gupta et al, 2002) 2) SMEDDS (Self Micro Emulsifying Drug Delivery Systems) Catarzi etal, 6th world meeting on Pharmaceutics, BioPharmaceutics and Pharmaceutical Technology, 2008 Glyburide Preparation: SME formulation was prepared by adding under continuous stirring Tween 20 and Labrafic Hydro WL (oil phase) and then distilled water to Glyburide solubilized in Transcutol. Glyburide tablets were prepared by direct ‘compression. The preparation with Neusilin® US2 resulted in improved flow, compact tablets and improved dissolution profilesisii2 Nousiin - Application Data 100 0 3 60 & 5 —* 3 40 essa * & ” —o— Ret. abet 20 a SME tablet < To tabet ¥ oo 20 40 60 Time ni Glyburide (GLY) dissolution profile fiom the different tablet formulations (Ref. Tablet — commercial GLY formulation; SME tablet— Glyburide SME formulation consisting of Labrafac Hydro® as oil phase, Tween 20 as surfactant and Transcuto!® as co- surfactant; TC tablet — Glyburide formulation consisting of Transcutol (TC). (Catarzi et al, 2008) Back to top VI. Hygroscopic velocity curve of Neusilin® 1) at 37°C, RH 53% uFL2, us2 #, NFL2N, NS2N, SGL sl Fu —— mi yeroscopie Mois Time (he) 2) at 37°C, RH 75%ssa Nousiin - Application Data Hygroscopic Moisture (8) ° 50 100 150 Time (he) Hygroscopic Moisture (6) ° 50 100 150 Time (he) Back to top VII. Hygroscopic equilibrium curve of Neusilin®sisii2 Nousiin - Application Data 60 wm us2/uri2 50 Molsture adsorption (%) ° 20 40 60 80 100 Relative Humicity (%) ‘The Hygroscopic velocity curve of different grades of Neusilin® indicate that Neusilin® is stable and do not absorb moisture up to 70% RH. Neusilin® remains flowable even after absorbing moisture up to 250% of its weight. 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