32 Pharmaceutical Technology EXCIPIENTS & SOLID DOSAGE FORMS 2004 w w w. p h a r m t e c h . c o m

n the past few years, many publishedarticles have detailed the develop-ments in the enteric coating process(1). Significant progress has beenmade in the coating of both hard gel-atin capsules and softgels (2–4), andsome progress has been made in thecoating of small particles such asbeads and granules. In addition, im-provement has been seen in the en-teric coating systems for tablets.Oneexample is the advances in applyingcolored latex enteric films.

In particular, there has been greatinterest in the enteric coating of as-pirin (6, 7). The resins available forenteric coating have undergone somechanges during the past five years.The current situation is as follows:● cellulose acetate phthalate is stillused and is applied from organicsolvent and as an aqueous latex

● hydroxypropyl methylcellulosephthalate is still used and is ap-plied from organic solvent or froman ammoniated aqueous solution

● polyvinyl acetate phthalate is stillavailable, but the manufacturer ofthis resin is now aggressively pro-moting an acrylic system

The Use of Acrylic Resinsfor Improved AqueousEnteric CoatingCharles A. Signorino,* Stephen Levine, Aaron Barkley, and Lou Forcellini

I

Recent technologyimprovements have madeacrylics the preferredsystem for the aqueousenteric coating of tablets.

SE

NS

IEN

T

C h a rle s A . Sig n orin o, P h D,is the president of EmersonResources, Inc ., 600 Markley St.,Norristown, PA 19401, tel.610.279.7450, ext. 223,charlie@emersonresources.com.Ste p h e n L e vin e is a seniorscientist, A a ro n B a rkle y is a group leader, and Lo u F orc e lliniis a manager of manufacturing, all atEmerson Resources, Inc .

*To whom all correspondence should be addressed .

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● hydroxypropyl methyl-cellulose succinate ac-etate is promoted as adispersible powder anda hot-melt resin

● shellac is useful as anammoniated solutionbut releases at a highpH (usually at pH !7.5)

● zein is no longer actively used forenteric coatings

● acrylics now are the system ofchoice and competition has madeseveral suppliers available. Chemi-cally similar alternate materialsare available, but their equivalencemust be tested.

Acrylics are the system of choiceHistorically, acrylic coatings havebeen unstable and have tended to ag-glomerate easily, making them diffi-cult to use. Because of the improve-ments that have been made to acrylicsystems and the techniques for ap-plying them, however, acrylics cur-rently are the most widely usedresins for aqueous enteric coatings.The resins are now more stable, andthey can now be used with glycerides

as detackifiers instead of talc, therebymaking their application much eas-ier. In addition, the ability to addcolor to the enteric coating has re-duced the complexity of the coatingprocess. Because color can now beincorporated into the enteric system,a final color layer over a clear entericfilm is no longer required.

A study using acrylic enteric emulsionsThe following study of the use ofacrylic enteric emulsions in aspirinprovides a clear indication of theimprovements that have been madein these systems.

Tablet cores. Three commonlymarketed dosages of aspirin tablets(81, 325, and 500 mg) were com-pacted as listed in Table I.

Aqueous coating formulations and

Table I: Tablet cores used in the study. Dosage Tablet Hardness(mg) weight (mg) (Kp) Friability

81 175.5 6–10 "0.4%325 390.0 8–12 "0.4%500 600.0 9–13 "0.4%

Table II: HPMC subcoat formulation.Material % %description Function Supplier Solids Solution FilmSpectrablend* 50857 Film/plasticizer Sensient 96.0% 12.50 100.00Deionized water, USP Medium Emerson 0.0% 87.50 0.00Total seal coat solution Seal coat Emerson 12.0% 100.00 100.00*Spectrablend (Sensient Technologies Co., South Plainfield, NJ) is a 96% solidsgranulation of HPMC and includes a plasticizer, which in the case of 50857 istriethyl citrate at 10% of HPMC.

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procedures for enteric aspirin. AnHPMC subcoat formulation for 81-,325-, and 500-mg aspirin tablets, aslisted in Table II, was applied as aseal coat to enhance the perform-ance of the aspirin tablets in accel-erated stability testing.

Subcoat procedure for all tablets.Thefirst step in the subcoat procedurefor all three dosages of aspirin was tomix Spectrablend into water until asolution was formed. Next, a 15-in.side-vented pan was charged with 2-kg aspirin cores and sprayed to 1.5%weight gain of solution at approxi-mately 20 g/min, with exhaust tem-perature at 45–50 #C, process air at250 cfm, atomizing air at 40 psi, andat a speed of 12–15 rpm.

Acrylic enteric topcoat formulationfor 81-mg aspirin. The acrylic enterictopcoat formulation for 81-mg as-pirin is listed in Table III.

Enteric topcoat procedure for 81-mgaspirin. The following procedure wasused to prepare the topcoat for the81-mg tablets:● Mix Eudragit (screened), Plasacryl

(screened), and triethyl citrate in80% of the additional water for 60min.

● Combine Spectraspray with theremaining 20% of the additionalwater.

● Combine the two suspensions andmix for 10 min; rescreen the result-ing suspension and continue gentlemixing throughout the coating run.

Table III: Acrylic enteric topcoat formulation for 81-mg aspirin.Material % % %description Function Supplier Solids Suspension Film

Eudragit Film Degussa 30.0 49.22 73.66L30D55* formationPlasacryl† Detackifier/ Emerson 20.0 4.91 4.90

plasticizerTriethyl citrate, Plasticizer Morflex 100.0 1.47 7.33PG, NFSpectraspray‡ Color Sensient 41.0 6.90 14.11Yellow SS-1243Deionized Spray Emerson 0.0 37.50 0.00water, USP mediumTotal enteric Enteric coat Emerson 20.0 100.00 100.00suspension* Eudragit L30D55 (Degussa, Röhm America, Piscataway, NJ) is a copolymer

dispersion of methacrylic acid and ethyl acrylate, at 30% solids. This filmsolubilizes at a pH $5.5.

† Plasacryl (Emerson Resources, Norristown, PA) is 20% solids emulsion, whichfunctions as a detackifier and as a plasticizer. Plasacryl is specially formulated foruse in aqueous acrylic coating suspensions.

‡ Spectraspray (Sensient Technologies Co.) is a pigment disperser. SS-1243 isspecifically designed for compatibility with acrylic emulsions.

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● Charge a 15-in. side-vented panwith 2030 g of subcoated 81-mg aspirin tablets and spray to 9%weight gain with a suspension at20–25 g/min, with inlet air at %55#C at 250 cfm, exhaust air at 35–40#C, atomizing air at 30 psi, and apan speed of 15–18 rpm.Enteric topcoat formulation for 325-

and 500-mg aspirin. The topcoat for-mulation for the 325- and 500-mgaspirin tablets is listed in Table IV.

Enteric topcoat procedure for 325-and 500-mg aspirin. The following

procedure was used to apply the en-teric topcoat to the 325- and 500-mg tablets:● Follow the topcoat suspensionpreparation procedure used forthe 81-mg aspirin.

● Charge a 15-in. side-vented panwith 2030 g of subcoated 325-mgaspirin tablets and spray to a 8%weight gain of suspension, as indi-cated above for the 81-mg aspirin,but with the pan speed at 15 rpm.

● Charge a 15-in. side-vented panwith 2030 g of subcoated 500-mg

Table IV: Acrylic enteric topcoat formulation for 325- and 500-mg aspirin. Material % % %description Function Supplier Solids Suspension Film

Eudragit Film Degussa 30.0 49.22 73.78L30D55 formationPlasacryl Detackifier/ Emerson 20.0 4.91 4.91

plasticizerTriethyl citrate, Plasticizer Morflex 100.0 1.47 7.35PG, NFSpectraspray Color Sensient 40.5 6.90 13.96Orange D-489Deionized water, Spray Emerson 0.0 37.50 0.00USP mediumTotal enteric Enteric coat Emerson 20.0 100.00 100.00suspension

Table V: Analytical testing results for 81-mg aspirin. Stability test Time Potency Free Diss.† Diss.†conditions Desiccant (months) % SA % acid % buffer %RT* Without 0 (initial) 98.3 0.1 0.4 100RT With 3 97.3 0.1 1.0 104RT Without 3 97.3 0.2 0.0 102Accelerated With 1 97.6 0.3 0.7 100Accelerated With 3 98.4 0.7 0.0 103Accelerated Without 1 98.7 0.5 0.9 97Accelerated Without 3 96.9 1.7 1.0 103* room temperature† dissolution

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aspirin tablets; spray to 7% weightgain, as indicated in the coatingprocedure for the 325-mg aspirin.The application of the subcoats and

topcoats to the tablets of all three sizeswas performed using a Compu-LabAccela-Cota tablet coater (ThomasEngineering Inc.,Hoffman Estates, IL)equipped with a 15-in. side-ventedpan and using a single 1⁄4 JAU spray gun(Spraying Systems Co, Wheaton, IL)with a SS 40100 liquid cap.

Stability study setupSamples of the three dosages of en-teric aspirin tablets were subjectedto a stability study. Samples weretaken monthly for analytical testing.

Bottling. Within seven days aftercoating, tablets of each dosage weretransferred to high-density poly-ethylene–sealed bottles, with andwithout desiccants. Tests were con-ducted under room temperature(RT) and accelerated stability con-ditions, and the bottles were desig-nated as time initial, one month,and three months.

Storage. The samples designed forRT storage were kept at 25 & 3 #Cand 40% relative humidity (RH).The samples in the accelerated sta-bility study were kept at 40 #C and75% RH. Bottles were kept sealeduntil testing. The RT samples werepulled from stability and tested

Table VI: Analytical testing results for 325-mg aspirin. Stability test Time Potency Free Diss. Diss.conditions Desiccant (months) % SA % acid % buffer %RT Without 0 (initial) 99.1 0.1 0.3 98.0RT With 3 101.2 0.1 1.0 104RT Without 3 99.6 0.1 0.0 103Accelerated With 1 99.3 0.2 1.3 99Accelerated With 3 102.7 0.6 1.0 103Accelerated Without 1 101.7 0.2 0.9 100Accelerated Without 3 102.4 0.5 1.0 102RT is room temperature

Table VII: Analytical testing results for 500-mg aspirin. Stability test Time Potency Free Diss. Diss.conditions Desiccant (months) % SA % acid % Buffer %

RT Without 0 (initial) 98.5 0.04 0.3 94RT With 3 99.3 0.1 1.0 99RT Without 3 101.8 0.1 1.0 97Accelerated With 1 97.4 0.1 1.6 95Accelerated With 3 101.7 0.2 1.0 99Accelerated Without 1 98.5 0.2 1.1 98Accelerated Without 3 98.1 0.8 1.0 100RT is room temperature

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three months after the date of pack-aging. The accelerated stability sam-ples were pulled from stability andtested one month and three monthsafter the date of packaging. OneTime 0 (initial) sample was tested.

Analytical testingAll testing was conducted withinseven days of sample pulls. Sampleswere tested for potency, free salicylicacid (SA), and USP enteric coateddissolution. Testing was performedby Boston Analytical Inc. (Salem,NH).

Aspirin potency. Tablets were testedby HPLC assay according to theUSP monograph for delayed-releaseaspirin tablets and reported interms of percentage of label claim.A passing result was 95.0–105.0% oflabel claim.

Limit of free SA.Using USP sali-cylic acid RS, USP assay results wereobtained in terms of percentage offree SA. A passing result was "3.0%free SA.

USP enteric coated dissolution. Withthe use of USP test 724, method B,six tablets of each sample weretested for enteric dissolution drugrelease as specified in the USPmonograph for delayed-release as-pirin tablets. A passing result for thein-gastric (acid) portion of the testis "10% dissolved. A passing resultfor the intestinal (buffer) portion ofthe test is !75% dissolved.

Analytical resultsThe analytical testing results for 81-325-, and 500-mg aspirin are listedin Tables V, VI, and VII, respectively.The analytical results for all aspirin

tablets of all three dosages werepassing results.

Conclusion.The analytical testing results for allthree dosage forms (81-, 325-, and500-mg aspirin), including boththose stored at room temperatureand those stored under acceleratedstability conditions, with and with-out desiccant, were within the speci-fied criteria for passing results. Thepositive results of these testsdemonstrate the advances that havebeen made in acrylic polymers foraqueous enteric coating of tablets.

References.1. C.A. Signorino, “Aqueous Enteric

Coating,” Pharm. Technol. Tableting &Granulation Yearbook, 1999.

2. L.A. Felton and J.W. McGinity, “En-teric Film Coating of Soft GelatinCapsules,” Drug Delivery Technol. 3(6), 34–39 (2003).

3. K. Thoma and K. Bechtold, “EntericCoated Hard Gelatin Capsules,” Cap-sugel Technical Bulletin, pp. 1–16(1986).

4. R. Pissinati and P. Oliviera, “EntericCoating Soft Gelatin Capsules bySpouted Bed,” Eur. J. Pharm. Bio-pharm. 55, 313–321 (2003).

5. K. Thoma and K. Bechtold, “Influenceof Aqueous Coatings on the Stabilityof Enteric Coated Pellets and Tablets,”Eur. J. Pharm. Biopharm. 47, 39–50(1999).

6. C.R. Cunningham and K.A. Fegley,“One-Step Aqueous Enteric CoatingSystems: Scale-up Evaluation,” Pharm.Technol. 25 (11), 36–44, (2001).

7. J. Yuan, N.M. Clipse, and S.H. Wu,“The Effects of Alternating Combina-tions of an Enteric Coating andHPMC as Inner and Outer Coatingson the Performance of Coated AspirinTablets,” Pharm. Technol. 27 (11),70–82 (2003).PT

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