EJECT
`
`CO PRESS
`
`ADJUST
`EIGHT
`
`DIE
`FILL
`
`CELGENE 2020
`APOTEX v. CELGENE
`IPR2023-00512
`
`

`

`PHARMACEUTICAL
`DOSAGE FORMS
`
`Tablets
`
`SECOND EDITION, REVISED AND EXPANDED
`
`In Three Volumes
`VOLUME3
`
`EDITED BY
`
`Herbert A. Lieberman
`H. H. Lieberman Associates, Inc .
`Consultant Services
`Livingston, New Jersey
`
`Leon Lachman
`Lachman Consultant Services
`Westbury, New York
`
`Joseph B. Schwartz
`Philadelphia College of Pharmacy and Science
`Philadelphia, Pennsylvania
`
`MARCEL DEKKER, INC.
`
`New York and Basel
`
`

`

`Rs~ 0 1
`, T.7 P-'16
`J cf8 9
`tJol . ..s
`
`ISBN: 0- 8247- 8300- X
`
`This book is printed on acid - free paper.
`
`Copyright C 1990 by MARCEL DEKKER, INC. All Rights Reserved
`
`Neither this book nor any part may be reproduced or transmitted in
`any form or by any means, electronic or mechanical, including photo (cid:173)
`copying, microfilming, and recording, or by any information storage
`and retrieval system, without permission in writing from the publisher.
`
`MARCEL DEKKER, INC .
`270 Madison Avenue, New York, New York 10016
`
`Current printing (last digit):
`10 9 8 7 6 5 4 3 2 1
`
`PRINTED IN THE UNITED STATES OF AMERICA
`
`

`

`78
`
`Porter and Bruno
`
`Changes that have occurred in coating processes reflect a desire to :
`
`Consistently obtain a finished product of high and reproducible
`quality
`Achieve processes in which the economics are maximized, particularly
`with respect to process times and equipment utilization
`
`While the methods for applying coatings to solid- dosage forms are
`varied, and some are described elsewhere in this book, this chapter will
`focus on the processes of sugar coating and film coating, and will discuss
`these processes with respect to :
`
`Raw materials
`Application techniques
`Potential problems
`Available coating equipment
`
`II. SUGAR COATI NG
`
`A.
`
`Introduction
`
`The process of sugar coating, which has its or1gms in the confectionery
`industry, is perhaps one of the oldest pharmaceutical processes still in
`existence .
`Although in recent years modernization of the process with respect to
`panning equipment and automation has taken place, sugar coating is still
`considered to be more of an art rather than a science .
`While methods (and materials) for coatings date back over 1000 years
`(early Islam makes reference to pill coatings based on mucillage of
`psyllium seeds), the current pharmaceutical process of sugar coating
`originated in the middle of the nineteenth century when sugar as a raw
`material became plentiful, and the forerunner of modern panning equip(cid:173)
`ment was invented .
`Although the tendency is to produce pharmaceutical coating pans from
`stainless steel, early pans were made from copper because drying was ef(cid:173)
`fected by means of an externally applied heat source. Current thinking,
`even with conventional pans, is to dry the coated tablets with a supply
`of heated air and to extract the moisture and dust -laden air from the
`vicinity of the pan .
`Although the sugar-coating process has experienced declining pop(cid:173)
`ularity in the United States, it is still retained by many companies world(cid:173)
`wide, since many advantages can be realized, including :
`
`Raw materials are inexpensive and readily available
`Raw materials are widely accepted with few regulatory problems (with
`the exception of perhaps colors)
`Inexpensive, simple equipment can be used
`Sugar-coated products are esthetically pleasing and have wide con(cid:173)
`sumer acceptability
`The process is generally not as critical (as film coating) and recovery
`( or rework) procedures are more readily accomplished
`
`

`

`Porter and Bruno
`
`coating of Pharmaceutical Solid - Dosage Forms
`
`79
`
`reflect a desire to :
`
`l reproducible
`
`imized, particularly
`1tilization
`
`:>sage forms are
`, this chapter will
`1g, and will discuss
`
`the confectionery
`rocesses still in
`
`ss with respect to
`1r coating is still
`
`< over 1000 years
`ucillage of
`:ugar coating
`sugar as a raw
`panning equip-
`
`coating pans from
`ie drying was ef(cid:173)
`iurrent thinking,
`: with a supply
`air from the
`
`declining pop (cid:173)
`companies world-
`
`· problems (with
`
`~ve wide con-
`
`g) and recovery
`1hed
`
`However, in spite of the relative simplicity of the sugar-coating
`process, it does have some potential shortcomings, for example :
`
`The size and weight of the finished product results in increased pack(cid:173)
`aging and shipping costs
`The brittleness of the coatings renders the coated tablets susceptible
`to potential damage if mishandled
`The achievement of high esthetic quality often requires the services of
`highly skilled coating operators
`The final gloss is achieved by a polishing step which can malrn im (cid:173)
`printing difficult
`The inherent complexity (from the standpoint of the variety of proce(cid:173)
`dures and formulations used) of the process makes automation
`more difficult
`
`In spite of these difficulties, many companies have made excellent use
`of modern process technology (including automation), so that the require(cid:173)
`ments of current GMPs, including documentation, are readily achieved with
`a high degree of reproducibility in the quality and performance of the
`finished product .
`
`B. Raw Materials Used in Sugar Coating
`
`As expected, the major ingredient used is sugar (sucrose), although this
`may be substituted by other materials (such as sorbitol) for low calorie/
`diabetic products (typically in the candy industry). Sugar-coating formu(cid:173)
`lations are for the most part aqueous .
`The sugar-coating process consists of various steps, each designed to
`achieve a particular function . Consequently, a variety of additives may
`be incorporated into each type of formulation . Examples of such additives
`are:
`
`Fillers ( calcium carbonate, talc, titanium dioxide)
`Colorants (dyes, aluminum lakes, iron oxides, titanium dioxide)
`Film formers (acacia, gelatin, cellulose derivatives)
`Antiadhesives (talc)
`Flavors
`Surfactants ( as wetting agents and dispersion aids)
`
`Although most of the coating formulations used in the sugar- coating
`process are applied as liquids, some (e . g . , dusting powders) are applied
`dry .
`A typical sugar- coating process encompasses five stages :
`
`1. Sealing
`2. Subcoating
`3, Grossing
`4. Color coating
`5. Polishing
`
`. While each of these stages is varied, the common feature throughout
`18 that the process requires repeated applications of coating liquid, each
`
`

`

`80
`
`Porter and Bruno
`
`application followed by a period during which the tablets are allowed to
`tumble freely to allow complete distribution of the coating materials, and
`finally, a drying period when moisture is removed from the coating prior
`to the next application .
`
`Sealing
`
`Most of the coating formulations used in the sugar - coating process are
`aqueous, whereas tablet cores are typically porous, highly absorbent, and
`formulated to disintegrate rapidly when they make contact with water .
`Consequently, if these cores are not appropriately protected at the outset,
`ultimate product stability (both physical and chemical) can be seriously
`compromised . The purpose of sealing is to offer this initial protection,
`and to prevent some tablet core ingredients from migrating into the coat (cid:173)
`ing, and ultimately spoiling the appearance of the final product.
`Sealing is accomplished by the application of a polymer- based coating
`(either by ladle or spray techniques) to the surfaces of the tablet cores .
`Examples of polymers that might be used include shellac, zein, hydroxy(cid:173)
`propyl methylcellulose (HPMC), polyvinyl acetate phthalate (PVAP), and
`cellulose acetate phthalate (CAP) . These are typically dissolved (at a
`15- 30% w /w concentration) in an appropriate organic solvent, preferably
`one of the denatured ethanol products .
`While use of shellac has been universal, this polymer can cause prob (cid:173)
`lems . One problem results from the fact that shellac can polymerize on
`storage, causing the solubility characteristics of the coating to change .
`This problem can either be minimized by incorporating PVP into the shellac
`formulation [ 1] or by using one of the other, more stable polymers ( such
`as PVAP) .
`When using any of the water - insoluble polymers as the basis for a seal(cid:173)
`coat formulation, it is important to apply only the minimum quantity of coat(cid:173)
`ing needed to give the appropriate protection; otherwise drug-release
`characteristics may well be affected .
`When the seal coat is applied by a ladle technique, detackifiers, such
`as talc, are often used to minimize the risk of "twinning" or clumping .
`Overzealous use of talc should be avoided, however, otherwise it might be
`difficult for the subsequent sugar coat to bond to the surface of the seal
`coat .
`Finally, if the final product is to have enteric properties, this result
`is usually achieved by using one of the enteric polymers ( such as PVAP
`or CAP) as the basis for the seal coat and ensuring that sufficient coat (cid:173)
`ing material is applied .
`
`Sub coating
`
`Subcoating is the first major step of the sugar-coating process and pro (cid:173)
`vides the means for rounding off the tablet edges and building up the
`core weight .
`It also provides the foundation for the remainder of the
`sugar-coating process, with any weakness in the final sugar coat often
`being attributable to weaknesses in the subcoat .
`In order to facilitate this buildup, subcoating formulations almost al (cid:173)
`ways contain high levels of fillers such as talc, calcium carbonate, cal -
`cium sulfate, kaolin, and titanium dioxide .
`In addition, auxiliary film
`formers such as acacia, gelatin, or one of the cellulose derivatives may
`
`

`

`'.Jorter and Bruno
`
`tre allowed to
`materials, and
`e coating prior
`
`process are
`absorbent , and
`with water .
`?d at the outset,
`be seriously
`tl protection,
`into the coat -
`1duct.
`- based coating
`e tablet cores .
`ein, hydroxy(cid:173)
`( PVAP), and
`;olved (at a
`1t, preferably
`
`an cause prob (cid:173)
`•olymerize on
`:\' to change .
`into the shellac
`>olymers ( such
`
`basis for a seal(cid:173)
`quantity of coat(cid:173)
`·ug-release
`
`1ckifiers, such
`r clumping .
`1ise it might be
`tee of the seal
`
`!S, this result
`uch as PVAP
`1fficient coat -
`
`ess and pro (cid:173)
`ing up the
`der of the
`: coat often
`
`ns almost al (cid:173)
`>onate, cal -
`:iliary film
`vatives may
`
`coating of Pharmaceutical Solid-Dosage Forms
`
`81
`
`Co ating
`
`Co ating
`
`...
`
`Schematic of examples of acceptable tablet-core shapes for
`Figure 1
`sugar coating .
`
`also be included in order to improve the structural integrity of the
`coating .
`It is important during subcoating to get effective coverage of the
`coating material over the tablet corners and on the edges if a quality re(cid:173)
`sult is to be achieved. To this end, selection of appropriate tablet
`shapes is important. Certainly, tablet shapes which minimize the corners
`(such as tablets compacted on deep concave punches or dual radius
`punches), as shown in Figure 1, can aid in effective coverage . Addi(cid:173)
`tionally, it is necessary to minimize tablet edge thickness, otherwise
`twinning will be more prevalent and incomplete edge coverage (by the
`coating) is likely to occur (Fig. 2) .
`
`Core
`
`can cause)}
`
`~ can cause
`
`Incomplete
`Edge Coverage
`
`Twinning
`
`Schematic example of poor tablet core shape for sugar coating.
`~~gure 2
`he twinning problem illustrated is more prevalent when using capsule(cid:173)
`shaped tablets . )
`
`

`

`82
`
`Table
`Process
`
`Examples of Formulations Used in the Lamination Subcoating
`
`Porter and Bruno
`
`(
`
`1
`
`I
`
`II
`
`Binder solutions
`
`Gelatin
`
`3.3% w/ w
`
`Gum acacia
`
`Sucrose
`
`Distilled water
`
`8. 7
`
`55.3
`
`32 . 7
`
`Dusting powders
`
`Calcium carbonate
`
`40 . 0% w/w
`
`Titanium dioxide
`
`Talc (asbestos free)
`
`Sucrose (powdered)
`
`Gum acacia
`
`5. 0
`
`25 . 0
`
`28.0
`
`2. 0
`
`6. 0%w/w
`8. 0
`
`45 . 0
`
`41.0
`
`1.0
`
`61. 0
`
`38 . 0
`
`Two main approaches to the process of subcoating are often practiced,
`depending on whether a lamination technique or a suspension subcoat
`formulation is used . Each has its distinct features and advantages .
`
`LAM INAT ION PROCESS . The lamination process is perhaps the older
`of the two techniques used, and involves alternate applications of binder
`solutions and dusting powder until the required level of coating is achieved .
`While materials and formulations for binder solutions and dusting powders
`are varied, some typical formulations are shown in Table 1.
`When using the lamination technique it is important to ensure that a
`careful balance is achieved between the relative amounts of binder solution
`and dusting powders used . Underutilization of dusting powders increases
`the risk of sticking and twinning, whereas overdusting can create tablets
`that have brittle coatings .
`While achievement of quality results with the lamination process typical (cid:173)
`ly requires employment of skilled operators , there is no doubt that this
`type of process can permit rapid buildup of the coating .
`On the downside, the lamination process can be messy, more difficult
`to use by less- skilled operators, and more difficult to automate .
`
`In simple terms, suspension
`S USPENSION SUBCOAT IN G PROCESS .
`subcoating formulations result from combining the binder and powder
`formulations used in the more traditional lamination process . Examples of
`a typical formulation are shown in Table 2.
`Use of the suspension subcoating approach reduces the complexity of
`the process, allowing it to be used effectively by less - experienced op (cid:173)
`erators, and ultimately facilitates automation of the process .
`
`

`

`Porter and Bruno
`
`coating of Pharmaceutical Solid-Dosage Forms
`
`83
`
`m Subcoating
`
`Table 2 Examples of Suspension Subcoating Formulations
`
`w
`
`w
`
`II
`
`6. 0% w/ w
`8. 0
`
`45 . 0
`
`41.0
`
`1.0
`
`61. 0
`
`38 . 0
`
`, often practiced,
`don subcoat
`ivantages .
`
`rhaps the older
`. tions of binder
`oating is achieved .
`lusting powders
`L.
`ensure that a
`f binder solution
`>Wders increases
`n create tablets
`
`1 process typical -
`mbt that this
`
`, more difficult
`,mate .
`
`1, suspens ion
`nd powder
`1. Examples of
`
`! complexity of
`irienced op -
`
`sucrose
`calcium carbonate
`
`Talc (asbestos free)
`
`Titanium dioxide
`
`Gum acacia
`
`Gelatin ( 120 bloom)
`
`Distilled water
`
`I
`
`II
`
`40 . 0% w/ w
`
`58 . 25%w/w
`
`20 . 0
`
`12. 0
`
`1.0
`
`2. 0
`
`25 . 0
`
`18 . 45
`
`1.00
`
`0. 01
`
`22 . 29
`
`Grossing ( or Smoothing)
`
`In order to manufacture a quality sugar- coated product, it is imperative
`that the surface of the coating be smooth and free from irregularities
`prior to application of the color coat.
`While the requisite smoothness may be achieved during the application
`of the subcoat, it is not unusual to find that further smoothing (prior to
`color coating) is necessary . Depending on the degree of smoothing re (cid:173)
`quired, the smoothing coating may simply consist of a 70% sucrose syrup,
`often containing titanium dioxide as an opacifier / whitening agent, and pos(cid:173)
`sibly tinted with other colorants to provide a good base for subsequent
`application of the color coat •
`If a substantial amount of smoothing is required, as in the case in
`which the subcoat tablets have a pitted surface, other additives ( such as
`talc , calcium carbonate, corn starch) may be used in low concentrations to
`hasten the s moothing process .
`
`Color Coating
`
`Many would agree that color coating is one of the most important steps in
`the sugar- coating process because of the immediate visual impact that is
`associated with overall quality .
`Use of appropriate colorants, which are dissolved or dispersed in the
`coating syrup , allows the desired color to be achieved . Two basic ap (cid:173)
`Pro_aches to coloring sugar- coating syrups exist , each giving rise to dif(cid:173)
`f:rmg coating techniques . These two approaches involve the use of
`either water - soluble dyes or water - insoluble pigments .
`d
`. Prior to the 1950s, soluble dyes were used extensively to achieve the
`esired color . This technique was handled by an experienced coater,
`~hho had acquired his skill over many years of work experience . Much of
`e color coating required 2 or 3 days, and unless handled properly, re (cid:173)
`~ulted in tablets that were nonuniform in color or mottled, since the soluble
`Ye can migrate to the surface during drying . Additionally, color
`
`

`

`84
`
`Porter and Bruno
`
`reproducibility from batch- to- batch was not predictable, and light sensi(cid:173)
`tivity with subsequent fading was also a problem when using dyes .
`The use of insoluble, certified lakes has virtually replaced the soluble
`dye in pharmaceutical tablet coating . Lakes have several advantages;
`namely, color migration on drying is eliminated, since lakes are insoluble,
`light stability is improved, mottled tablets are a rare occurrence, and coat(cid:173)
`ing time is substantially shortened . While lakes are insoluble, they are
`not totally opaque . Consequently, coloring properties can be optimized by
`combining lakes with opacifiers such as titanium dioxide . The most effi(cid:173)
`cient process for color coating involves the use of predispersed, opacified
`lake suspensions . By varying the ratios of lake and opacifier, various
`shades can be produced .
`
`DYE-COATING PROCESS . The features of a typical sugar- coating
`process that utilizes water-soluble dyes as colorants include :
`
`Sequential application of coating syrups containing specific dye concen(cid:173)
`trations (typically, as coating progresses, dye concentrations in
`the syrup may be increased until the target color is achieved)
`Addition of a quantity of colored syrup (at each stage) that is suf(cid:173)
`ficient to just wet the total tablet surface, followed by gentle dry(cid:173)
`ing to achieve requisite smoothness and prevent color migration
`Employment of relatively low concentrations of colorant (necessary to
`achieve final color uniformity), resulting in a requirement to make
`anywhere up to 50 separate color syrup applications (particularly
`for dark colors)
`
`There is no doubt that in the hands of a skilled operator the quality
`of sugar- coated tablets that employ the dye-coating method are difficult to
`match (this is particularly true from the standpoint of "cleanliness, 11 depth ,
`and "brilliance" of the final color) .
`However, such a process is not without its difficulties , namely :
`
`Color migration problems (resulting from either underdrying or too
`rapid a drying) are commonplace .
`Color variability, across the surface of individual tablets , which occurs
`as the result of unevenness of the subcoat layer and transparency
`of the color coat .
`Tablet- to - tablet color variability which may result because the trans (cid:173)
`parent coloring system has not been uniformly distributed .
`Batch - to- batch color variation which is likely to occur because of
`variability in the total quantity of color applications made, or as a
`result of small differences in amount of colorant weighed out for
`each batch (water- soluble dyes produce very intense colors and a
`little goes a long way) .
`The process is time consuming (because of the slow drying required
`and the need to make so many individual color applications) .
`
`PIGMENT- COATING PROCESS. Pigments have demonstrable advantages
`over water - soluble dyes, two important ones being :
`
`1. Lack of solubility in aqueous media (which eliminates color migra(cid:173)
`tion on drying)
`2. Superior light stability
`
`

`

`Porter and Bruno
`
`and light sensi(cid:173)
`sing dyes .
`placed the soluble
`l advantages;
`ces are insoluble,
`,urrence, and coat(cid:173)
`luble, they are
`m be optimized by
`The most effi (cid:173)
`:persed, opacified
`.cifier , various
`
`sugar-coating
`tde :
`
`•ecific dye concen(cid:173)
`mcentrations in
`· is achieved)
`e) that is suf-
`~d by gentle dry (cid:173)
`!olor migration
`t ( necessary to
`uirement to make
`,ns (particularly
`
`ator the quality
`d are difficult to
`eanliness, " depth ,
`
`;, namely :
`
`jrying or too
`
`ets, which occurs
`md transparency
`
`mse the trans (cid:173)
`tributed .
`because of
`1s made, or as a
`eighed out for
`1se colors and a
`
`•ying required
`1lications) .
`
`coating of Pharmaceutical Solid-Dosage Forms
`
`85
`
`However, because pigments are discrete, insoluble particles, careful
`ttention must be paid to the pigment-dispersion process . Hence, the pop(cid:173)
`\arity of commercially available pigment - dispersion concentrates .
`u
`Some of the major characteristics of sugar- coating formulations and
`processes when pigment colorant systems are used include :
`
`use of a single- color concentration throughout the color- coating
`process, thus making it easier to achieve the target end color (in
`order to obtain a different color, it is necessary to vary the ratios
`of the lake pigments with respect to the opacifier, titanium
`dioxide)
`Achievement of batch color uniformity after only a few applications of
`colored syrup (often color development is complete after eight to
`10 applications, and the remaining five to seven applications are
`simply used to smooth off the tablet surface)
`Reduced drying times resulting from the fact that the insoluble color(cid:173)
`ants do not migrate on drying, and thus can be dried more
`rapidly
`Overall shortened color- coating process as a result of reduced number
`of color applications and shortened drying times
`
`One should, however, be aware of what some might construe to be dis (cid:173)
`advantages with pigment coloring systems and the associated coating
`process :
`
`Colorants derived from pigments (especially when lakes are used in
`combination with titanium dioxide) are generally not as bright or
`clean-looking as those obtained with soluble colorants .
`If the pigment color- coating process is rushed, it is relatively easy to
`produce rough tablets that are difficult to polish .
`There is a need to ensure that pigments are effectively dispersed in
`the coating syrup (certainly, pigment color concentrates eliminate
`this problem), otherwise color "specking" might be a problem .
`Since most pigment coloring systems contain lakes (which are typically
`acidic), it is inadvisable to keep coating systems hot for any
`length of time once the color has been added; otherwise excessive
`amounts of invert sugar will be formed .
`
`With the exception of the first of these problems, all the others can
`easily be avoided, and thus advantages of the pigment coating process
`tend to prevail, making it the process of choice .
`Summarizing these advantages, they are:
`
`Greater ability to get a uniform color on the surface of each tablet
`Greater batch-to- batch color uniformity
`Significant reduction in thickness of the color coat
`Significant reduction in processing time
`
`rable advantages
`
`Polishing (Glossing)
`
`es color migra -
`
`Since freshly color- coated tablets are typically dull (i.e . , they have a
`mat~e surface finish), it is necessary to polish them in some way to
`achieve the gloss that is typical of finished sugar- coated tablets .
`
`

`

`86
`
`Porter and Bruno
`
`While methods to achieve a desirable gloss tend to vary considerably,
`it is generally recommended that tablets should be trayed overnight (prior
`to polishing) to ensure that they are sufficiently dry . Excessively high
`moisture levels in tablets submitted for polishing will :
`
`Make achievement of a good gloss difficult
`Increase the risk of "blooming" and "sweating" over longer periods of
`time
`
`Glossing or polishing can be carried out in various types of equipment
`(e . g . , canvas- or wax -lined pans) , including that used for applying the
`sugar coating itself (which is more typical in automated processes) .
`Polishing systems that may be used include :
`
`Organic- solvent- based solutions of waxes (beeswax, carnauba wax,
`candelilla wax)
`Alcoholic slurries of waxes
`Finely powdered mixtures of dry waxes
`Pharmaceutical glazes (typically alcohol solutions of various forms of
`shellac, often containing additional waxes)
`
`Printing
`
`If sugar- coated tablets are to be further identified with a product name,
`dosage strength, or company name or logo, this has to be accomplished by
`means of a printing process .
`Typically, such printing involves the application of a pharmaceutical
`branding ink to the coated tablet surface by means of a printing process
`known as offset rotogravure .
`Sugar- coated tablets may be printed either before or after polishing,
`with each approach having its advantages and disadvantages . Printing
`prior to polishing enables the ink to adhere more strongly to the tablet
`surface, but any legend may subsequently be removed by either friction or
`as a result of contact with organic solvents during the polishing process .
`Printing after polishing avoids the problem of print rub-off during polish(cid:173)
`ing, but branding inks do not always adhere well to the waxed tablet sur(cid:173)
`face . Adhesion of printing inks can be enhanced by application (prior to
`printing) of a modified shellac, preprint base solution .
`
`C. Applicat ion Techn iques
`
`Application of sugar coatings to pharmaceutical tablets has long been con(cid:173)
`sidered one that requires a significant amount of skill on the part of the
`operator . While this philosophy has a lot of truth in it, and while it is
`certainly difficult for untrained operators to achieve quality results, the
`employment of special techniques (such as the use of suspension subcoat
`formulations and coatings colored with proprietary pigment dispersions)
`makes quality results achievable even for less - skilled operators .
`While many different types of coating formulation (Sec . II. B) will be
`applied during the coating process, similarities in application exist for each
`of them .
`The basic application procedure in each case involves three steps in
`sequence :
`
`

`

`Porter and Bruno
`
`ry considerably,
`overnight (prior
`xcessively high
`
`:mger periods of
`
`pes of equipment
`,r applying the
`·ocesses) .
`
`.rnauba wax,
`
`~ious forms of
`
`product name,
`accomplished by
`
`harmaceu tical
`inting process
`
`'ter polishing,
`s . Printing
`to the tablet
`ither friction or
`,hing process .
`during polish -
`xed tablet sur-
`1tion (prior to
`
`mg been con(cid:173)
`~ part of the
`l while it is
`results, the
`sion subcoat
`ispersions)
`,rs .
`I.B) will be
`exist for each
`
`·ee steps in
`
`coating of Pharmaceutical Solid-Dosage Forms
`
`87
`
`1. Application of an appropriate volume ( sufficient to completely
`cover the surface of every tablet in the batch) of coating liquid
`to a cascading bed of tablets
`z. Distribution of the coating liquid uniformly across the surface of
`each tablet in the batch
`3. Drying of the coating liquid once uniform distribution is achieved
`
`Specific details of actual procedures adopted may vary from company(cid:173)
`to-company . However, the ultimate goal in each case is to ensure that
`the coating is uniformly distributed throughout the batch. Although this
`goal may be facilitated by the manner in which the coating liquid is ap (cid:173)
`plied, and by manual stirring of the wet tablets to help eliminate "dead
`spots" (regions in the tablet bed that are difficult to reach with the coat(cid:173)
`ing liquid) , the main mechanism for distribution of the coating liquid re(cid:173)
`lates to the shearing action that occurs as tablets cascade over one
`another .
`For the greatest period of time, sugar- coating liquids were applied
`manually by allowing premeasured quantities of coating liquid to be poured
`across the moving tablet bed .
`In recent times, there has been a greater
`reliance on mechanical dosing techniques , involving the use of spray guns
`or dosing "sparges" (Fig . 3) .
`One of the major misconceptions concerning the use of mechanical
`dosing techniques, particularly spray guns, is that they can exert a
`major influence on uniformity of distribution of the sugar- coating liquid.
`Again, it is important to emphasize that the main factor controlling distribu (cid:173)
`tion of the coating liquid relates to contact between the cascading tablets,
`and transfer of liquid from one tablet to another as the result of this con(cid:173)
`tact. Thus, particularly when using spray guns, it is not necessary to
`finely atomize the coating liquid in order to ensure effective distribution
`of that liquid .
`Indeed, excessive atomization can cause "fogging" where
`much of the coating liquid can end up on the walls of the pan rather than
`on the tablets . Consequently, many advocates for the use of spray guns
`simply allow the liquid to stream from the nozzle . For this reason, use
`of a device similar to that shown in Figure 3 can be equally effective and
`less expensive than using spray guns .
`Summarizing, since coating uniformity is achieved as the result of
`tablet-to - tablet transfer of liquid coating material , it is not necessary for
`each tablet to pass through the zone of application ( which is a necessity
`in the film-coating process) . Factors which influence coating uniformity in
`the sugar- coating process are that:
`
`The coating material remains fluid until it is spread across the surface
`of every tablet in the batch .
`Sufficient volume of coating liquid is applied to ensure that every
`tablet in the batch is capable of being wetted (thus liquid volumes
`may have to be changed as the process progresses in order to
`reflect changes in tablet size and drying conditions) .
`The coating pan exhibits good mixing characteristics , particularly so
`that dead spots are avoided (many coating pans of conventional
`design, i.e . , the traditional pear- shaped design, may have to be
`modified by inclusion of mixing baffles, otherwise mixing may have
`to be augmented by manual stirring of the tablets by the op(cid:173)
`erator) .
`
`

`

`88
`
`Porter and Br,u 110
`
`Figure 3
`
`Figure showing a dosing sparge for sugar coating.
`
`

`

`Porter and Bruno
`
`Coating of Pharmaceutical Solid-Dosage Forms
`
`89
`
`Problems in Sugar Coating
`
`D.
`1 any coating process, a variety of problems may arise . Often such prob-
`l n ms may be related to formulation issues that have been compounded by
`e
`•
`those associated with processing .
`
`Problems with Tablet Core Robustness
`
`The attritional effects of any coating process on tablet cores is well
`understood . Consequently, tablet cores must be sufficiently robust to
`resist the stress to which they will be exposed during coating.
`With this in mind, particular attention must be paid to important tablet
`physical properties such as hardness (diametral crushing strength), fria(cid:173)
`bility, and lamination tendency . Failure to address these issues is likely
`to result in a situation in which tablet fragmentation occurs during the
`coating process .
`Tablet fragmentation is not only a problem from the standpoint that
`the broken tablets will obviously not be saleable (and thus would have to
`be inspected out) , but additionally, the broken fragments may typically be(cid:173)
`come "glued" (because of the adhesive nature of the coating fluids) to the
`surface of undamaged tablets (Fig . 4); thus spoiling a significant portion
`of the batch .
`
`Quality Problems with Finished Tablets
`
`CHIPPING OF COATINGS. Sugar coatings are inherently brittle and
`thus prone to chipping if mishandled . Addition of small quantities of
`polymers ( such as cellulosics, polyvinyl pyrrolidone, acacia, or gelatin) to
`one or more of the various coating formulations often helps to improve
`structural integrity, and thus reduces chipping problems .
`Excessive use of insoluble fillers and pigments tends to increase the
`brittleness of sugar coatings, and thus should be avoided where possible .
`
`CRACKING OF THE COATING . Tablet cores that expand, either dur(cid:173)
`ing or after coating, are likely to cause the coating to crack (Fig. 5) .
`Such expansion may result from moisture absorption by the tablet core,
`or may be caused by stress- relaxation of the core after compaction (a
`Phenomenon which is known to occur, for example, with ibuprofen) .
`Moisture sorption can be minimized by appropriate use of a seal coat,
`whereas expansion due to postcompaction stress relaxation can be resolved
`by extending the time between the compaction event and commencement of
`sugar coating .
`
`Inability to dry sugar coatings properly,
`NONDRYING COATINGS .
`especially those based on sucrose, is often an indicator that excessive
`~evels (greater than 5%) of invert sugar is present.
`Inversion of sucrose
`is exacerbated by keeping sucrose syrups at elevated temperatures under
`acidic conditions for extended periods of