ExcipientFest Americas 2013 April 30th SHELLAC A Versatile Film Coating System 1 HS2 • Sensient • Sensient’s fully formulated coating systems • Spectrablend • Spectrablend II • Spectrafilm • Spectrablend CC (Calcium Carbonate) • Spectrablend MB (moisture barrier) • Protect EN • Shellac-based formula • Shellac • Shellac as a natural versatile resin • About Shellac • Offers tablet coating benefits • Functional properties • Enteric • Sealant • Barrier protection • Taste & odor masking • Aesthetic and immediate release properties DISCUSSION OVERVIEW 2 1 Slide 2 HS2 period after protection Houston Smith, 3/28/2013 ExcipientFest Americas 2013 April 30th • 35 locations around the world • Efficient product • Global resources commercialization • Ultimate confidence in your brand, whether regional or global in distribution 3 Sensient Pharmaceutical is a global leader in superior coating systems, brand‐defining color solutions, and enhanced product performance for the pharmaceutical and nutraceutical markets. 4 2 ExcipientFest Americas 2013 April 30th SENSIENT PRODUCTS COATINGS SPECTRAFILM™ SPECTRABLEND™ SPECTRABLEND II™ A customizable, pre‐blended A customizable, fully formulated A customizable, fully color system. film coating system that consists formulated film coating system of film forming polymer(s), that provides additional plasticizer, and colorant. benefits to Spectrablend. SPECTRABLEND CC™ PROTECT ™SPECTRABLEND MB™ A low‐dust, high solids, An enteric, aqueous coating A film coating for oral solid‐ titanium dioxide‐free, opaque system optimized for use on dosage forms that require coating system. tablets, soft gels, and two‐piece protection from environmental hard capsules. moisture (prevention of influx). 5 HS1 ABOUT SHELLAC ORIGIN • It takes about 300,000 lac • Shellac, also know as Lac is bugs to make 1 kg of shellac cultivated in various countries1: flakes. • India #Name 1 Lac 2 Shellac, handmade (Excluding button lac) • Thailand 3 Shellac, machine made (Excluding garnet lac) 4 Seedlac • China 5 Stick lac 6 Dewaxed & Decolourized lac • Vietnam 7 Bleached lac 8 Gasket lac 9 Button lac 10 Garnet lac 11 Other lac 12 Lac-dye 13 Aleuritic acid 14 Shellac wax 6 3 Slide 6 HS1 comma after India Houston Smith, 3/28/2013 ExcipientFest Americas 2013 April 30th ABOUT SHELLAC ORIGIN • Laccifer Lacca Kerr (Family Coccidae) insects secrete resin on bark (Lac Host) and protect themselves into the adult stage by forming cocoons. • The female lac insects are wingless; however, the male insects swarm impregnating female lac insects and then die.7 • After impregnation, they attach • The stick lac covered branches are pruned pincers under the bark of the host from the host trees and sent for trees to feed while depositing & processing. forming the cocoon of lac resin around them from cranial glands. • Image reference4 7 ABOUT SHELLAC ORIGIN • The Lac encrustations removed from the bark (sticklac/grainlac) is washed in an aqueous media to remove excess erythrolaccin & laccaic acid (red dyes) from the sticklac then filtered and dried. • Historically, colonial ‘British Red Coats’ used Laccaic acid to dye uniforms red. • Today, Laccaic acid is sold principally to the Japanese market for use in dying ketchup. • Image reference4 8 4 ExcipientFest Americas 2013 April 30th ABOUT SHELLAC PROCESSING METHODS Seedlac Three principle processing methods: Heat Solvent ‐ (De‐Waxing) Bleached Heat Processing Seedlac is heated, filtered and then forced through rollers forming thin sheets, dried & broken into flakes Solvent Extraction (De‐Waxing) Seedlac is refluxed with ethanol for an hour, filtered, and then carbon treated to decolorize the shellac. Ethanol is then removed and the shellac is sent through rollers ‐ dried sheets are then flaked. Bleached Processing Seedlac is made alkali‐soluble, filtered then bleached with sodium hyperchlorite. Shellac is precipitated from dilute sulfuric acid, filtered & water washed. The shellac is dried, and ground into a white powder. 9 ABOUT SHELLAC PROCESSED SHELLAC 10 5 ExcipientFest Americas 2013 April 30th HS3 ABOUT SHELLAC CHEMICAL STRUCTURE • Shellac: esters of polyhydroxy carboxylic acids3 • The Ester of Shellac (image to the right) • Main components are: • Aleuritic Acid (35%) R • Jalaric Acid (25%) • Shellolic Acid (8%) • Butolic Acid (8%) • Aleuritic Acid • Perfume manufacturers substitute Civitone with extracted Aleuritic Acid 11 HS4 SHELLAC VERSATILE USES • Pharmaceutical & Nutraceutical Industries • Enteric: intestinal release (acidic properties resist stomach acids) • Sealant • Decreased moisture permeation • Masking taste and odor, • Immediate release & aesthetic film properties • Industrial Uses: Sealant, Lacquer –primer for wood • Food Industry: Candies –Sealant, coating, oxygen barrier for fruits & glaze 12 6 Slide 11 HS3 acids3? Houston Smith, 3/28/2013 Slide 12 HS4 colonic release? I thought it was intestinal release? Houston Smith, 3/28/2013 ExcipientFest Americas 2013 April 30th Shellac – Product Diversification • Pharmaceutical • Nutraceutical 13 HS5 FUNCTIONAL ENTERIC PROPERTIES • Polymers used in enteric shellac coating systems6: • Polyvinyl alcohol, (PVA) – Results: in film cracking and water diffusion • Hydroxypropyl methylcellulose (HPMC) – Results: Increases the film voids which increases the drug release • Carbomer 940 – Results: Swells leading to diffusion and premature drug release • Sodium Alginate – Results: Passes USP enteric testing • Experimentation • De‐waxed & De‐colorized shellac NF (de‐waxed orange shellac) – aqueous solution • Plasticizers added to sustain stable enteric properties with Sodium Alginate 14 7 Slide 14 HS5 same indent for "Added plasticizers"? Houston Smith, 3/28/2013 ExcipientFest Americas 2013 April 30th FUNCTIONAL ENTERIC PROPERTIES • Enteric coated soft‐gel • Dissolution Protocol USP 35 –NF 30 followed • 2040 Disintegration and Dissolution of dietary supplements • Simulated Gastric Testing (SGF) o Passes 60 minutes and 120 minutes • Simulated Intestinal Testing (SIF) o Passes disintegration in 60 minutes 15 HS6 FUNCTIONAL ENTERIC PROPERTIES • Stability of Enteric coated soft‐gels Disintegration in SIF ‐ USP 35 60 50 Time 40 30 Rupture 20 SIF 10 0 ‐1 4 9 141924 Testing: months RT H2 25°C/60% RH H4 40°C/75% RH 16 8 Slide 16 HS6 what is <2040>? Houston Smith, 3/28/2013 ExcipientFest Americas 2013 April 30th HS7 FUNCTIONAL SEALANT PROPERTIES Ibuprofen Release Profile: Uncoated & Shellac Coated 100 90 Uncoated 6.8 pH 80 Uncoated 5.5 pH 70 UV 60 3% wt gain 6.8 pH via 50 3% wt gain 5.5 pH 40 Release % 30 3% wt gain 1.2 pH 20 10 0 0 5 10 15 20 25 30 35 40 45 50 55 60 Time (min) 17 HS8 FUNCTIONAL MOISTURE BARRIER PROPERTIES Permeation Results for Shellac 0.12 0.1 0.08 Absorption 0.06 Actual Absorption Predicted Permeation 0.04 Moisture 0.02 0 0123456 Percent Weight Gain 18 9 Slide 17 HS7 Why would you only seal coat if there is little protection in the mouth and not as much protection in the stomach as Protect? Why not enteric coat? Houston Smith, 3/28/2013 Slide 18 HS8 I can't tell what this slide is about. I would annotate the two curves and expand the title definition. Houston Smith, 3/28/2013 ExcipientFest Americas 2013 April 30th HS9 FUNCTIONAL BARRIER PROPERTIES • Reference: • According to the Berlin College of Pharmacy, 5 o Shellac‐coated tablets showed . Decreased water uptake rates than HPMC‐coated systems at the same coating level. Increased stability of acetaminophen compared with HPMC‐ coated systems, irrespective of the storage humidity • Overall, lower shellac coating levels were required to achieve the same degree of drug protection • Shellac coatings effectively masked the unpleasant taste of acetaminophen tablets5 19 FUNCTIONAL TASTE ‐ MASKING PROPERTIES Shellac as a Taste‐Maskant 8.0 7.0 6.0 5.0 Released 4.0 3.0 2.0 Ibuprofen 1.0 % 0.0 0 10203040506070 ‐1.0 T = seconds Uncoated Ibuprofen at 5.5 pH 3% shellac wt gain pH 5.5 Uncoated Ibuprofen at 6.8 pH 3% shellac wt gain pH 6.8 • According to the International Journal of Drug Testing, the normal pH range for saliva is considered to be 5.6 to 7.9. Children have higher pH, Adults average 6.5. 20 10 Slide 19 HS9 did you mean to switch fonts? Indention is different on "Shellac coatings" Houston Smith, 3/28/2013 ExcipientFest Americas 2013 April 30th HS11 FUNCTIONAL IMMEDIATE RELEASE PROPERTIES • Creating Immediate Release (IR) • Incorporate other polymers ( 5 to 50% w/w) • Hydroxypropyl methylcellulose (HPMC) • Methyl cellulose (MC) • Hydroxypropyl cellulose (HPC) • Polyvinyl pyrrolidone (PVP) • Modified starches & Maltodextrin • Natural gums • Benefits • Increased • Solutions solids • Lower viscosity • Finer atomization • Coating uniformity • Production through‐puts • Glossiness • Aesthetic appeal 21 ABOUT SHELLAC REGULATORY • Shellac is an approved food • Flexible product development additive: • Global commercialization • US & Europe • Natural coating system • Shellac is listed: • USP & European Pharmacopoeia • JP, FCC, E904 22 11 Slide 21 HS11 use commas at the ends or don't, not both ways. Houston Smith, 3/28/2013 ExcipientFest Americas 2013 April 30th ABOUT SHELLAC REFERENCES 1. HTTP://WWW.DMSHELLAC.COM/ABOUT_SHELLAC.HTML 2. HTTP://WWW.DGFT.ORG/ITC_HS_CODE.HTML. 3. S.K. SHARMA, S. K. SHUKLA & D. N. VAID, DEFENCE SCIENCE CENTRE, METCALFE HOUSE, DELHI DEF SCI J. VOL 33, NO. 3, JULY 1983, PP 261‐271 4. SMITH & RODGER LTD, IMAGES: HTTP://WWW.FRENCHPOLISHES.COM/CONTACT.HTM 5. PEAMCHOB N, SIEPMANN J, BODMEIER R., COLLEGE OF PHARMACY, FREIE UNIVERSITAET BERLIN, BERLIN, GERMANY: PHARMACEUTICAL APPLICATIONS OF SHELLAC: MOISTURE‐PROTECTIVE AND TASTE‐MASKING COATINGS AND EXTENDED –RELEASE MATRIX TABLETS. HTTP://WWW.NCBI.NLM.NIH.GOV/PUBMED/14570313 6. QUSSI B, SUESS WG, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, INSTITUTE OF PHARMACY, UNIVERSITY OF LEIPZIG, LEIPZIG, GERMANY: DRUG DEV IND PHARM. 2005 JAN; 31(1): 99‐108. HTTP://WWW.NCBI.NLM.NIH.GOV/PUBMED/15704861 7. TONY CHUFFO, CORIELL ASSOCIATES INC: E‐MAIL CORRESPONDENCE ON APRIL 1, 2013 6:20PM. 23 ABOUT ACKNOWLEDGEMENTS • Excipientfest 2013 Forum • Sensient Laboratory Personnel for Product Testing • All supporting references & correspondences 24 12 ExcipientFest Americas 2013 April 30th THANK YOU 25 13.