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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 (24), 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 still
used 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
Charles A. Signorino, PhD,is the president of EmersonResources,
Inc., 600 Markley St.,Norristown, PA 19401, tel.610.279.7450, ext.
223,[email protected] Levine is a
seniorscientist, Aaron Barkley is a group leader, and Lou
Forcelliniis a manager of manufacturing, all atEmerson Resources,
Inc.
*To whom all correspondence should be addressed.
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E xc i p i e n t s & S o l i d D o s a g e Fo r m s
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) Friability81 175.5 610 0.4%
325 390.0 812 0.4%500 600.0 913 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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Pharmaceutical Technology EXCIPIENTS & SOLID DOSAGE FORMS
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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 4550 C, process air at250 cfm, atomizing air at 40
psi, andat a speed of 1215 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, Rhm 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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E xc i p i e n t s & S o l i d D o s a g e Fo r m s
Charge a 15-in. side-vented panwith 2030 g of subcoated 81-mg
aspirin tablets and spray to 9%weight gain with a suspension at2025
g/min, with inlet air at 55C at 250 cfm, exhaust air at 3540C,
atomizing air at 30 psi, and apan speed of 1518 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 suspension
preparation 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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E xc i p i e n t s & S o l i d D o s a g e Fo r m s
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 14 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-ethylenesealed 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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Pharmaceutical Technology EXCIPIENTS & SOLID DOSAGE FORMS
2004 39
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
95.0105.0% 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), 3439 (2003).
3. K. Thoma and K. Bechtold, EntericCoated Hard Gelatin
Capsules, Cap-sugel Technical Bulletin, pp. 116(1986).
4. R. Pissinati and P. Oliviera, EntericCoating Soft Gelatin
Capsules bySpouted Bed, Eur. J. Pharm. Bio-pharm. 55, 313321
(2003).
5. K. Thoma and K. Bechtold, Influenceof Aqueous Coatings on the
Stabilityof Enteric Coated Pellets and Tablets,Eur. J. Pharm.
Biopharm. 47, 3950(1999).
6. C.R. Cunningham and K.A. Fegley,One-Step Aqueous Enteric
CoatingSystems: Scale-up Evaluation, Pharm.Technol. 25 (11), 3644,
(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),7082 (2003).PT
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