4’?4’?
`
`
`
`‘‘
`
`
`
`
`
`
`
`
`
`

`
`in the year 1885 by Joseph P Remington,
`to Act of Congress,
`Entered according
`in the Office of the Librarian
`at Washington,
`DC
`of Congress,
`Copyright
`1889,1894, 1905,1907,1917, by J011eph P Remington
`1926, J 936, by Joseph P Remington
`Estate
`Copyright
`College of Pharmacy and Science
`1948, 1951, by The Philadelphia
`Copyright
`
`of Pharmacy and
`College
`1960, 1965, 1970, 1975, 1980, 1985, by The Philadelphia
`Copyright <ell956,
`Science
`
`All Rights Reserved
`
`Library of Congress Catalog Card No 60-53334
`
`ISBN 0-912734-03-5
`
`of the t.e:r.t of USP XX, NF XV, fllld l/SJ\N umllhP liSP Jlirtiollttl')'
`nf nwc
`The u.�e of porlwns
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`of quototio11
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`or b.v ob.�nlt•srrrtu• rP.�IIIting
`the OrtJIIIlal conlt•xt
`fr!lm
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`t�f a supplemt'nl
`publi<"otilln
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`of nr u 3Ub�titute
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`for thl' trffictal
`1-'ormulary (NF) In lhP. PI>Pnl 11f a11y di{ft•rPMfl t>r discrt•pcmcy l�etrt P/! 11 thr rurrl'nt
`11f{iciul
`punlY, f)fii'NIIJIIllll and label me /tJr dntgs and
`USP r>r NP �tamlards of �trength,
`l{llalitv,
`a/ them herPin,liiP c-untt>:rt and r/fl'd 1Jf tltc 11f/icial
`c:umpl'ndia shalt
`n•prPsPnlaliotL�
`prct'Oil.
`
`Company, Easton, Penrnyluania
`Printed in the United Slates of America by the Ma<"k Printtng
`
`

`
`.Ac-
`
`don,
`
`llan,
`
`>hie,
`
`non,
`
`rbor
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`non,
`
`A.ca-
`
`CHAPTER 90
`
`Oral Solid Dosage Forms
`
`
`
`"()b•rt E King, PhD
`
`
`
`
`
`Profe-ssor of lndustrlol Phormoc:y
`
`Jos•ph D Schwort.z, PhD
`
`Professor of Pharmoce>ullc.s
`
`
`
`Philadelphia Colle-ge of Pharmacy ond Science
`Philadelphia,
`
`PA 19104
`
`orally administered Drug substances are most frequently
`
`
`
`by means of solid dosage forms such as tablets and capsules.
`
`
`Large-scale production methods used for their preparation
`
`
`
`
`of other as described later in the chapter require the presence
`
`materials in addition to the active ing:t:'edients. Additives may
`
`
`
`to enhance the physical also be included in the formulations
`
`
`
`appearance, improve stability, and aid in disintegration after
`
`
`
`administration. These supposedly inert ingredients, as well
`
`
`as the production methods employed, have been shown in
`
`
`' some cases to influence the release of the drug substances_!
`
`
`Therefore care must be taken in the selection and evaluation
`
`
`of additives and preparation methods to ensure that the
`
`
`
`physiological availability and therapeutic efficacy of the active
`
`ingredient will not be diminished.
`number of cases it has been shown that the drug
`In a limited
`
`
`
`
`substance's solubility and other physical characteristics _have
`
`
`influenced its physiological availability from a solid dosage
`
`
`
`form. These characteristics include its particle size, whether
`
`
`
`it is amorphous or crystalline, whether it is solvated or non­
`form. After clinically
`
`solvated, and its polymorphic
`effective
`
`
`
`formulations are obtained, variations among dosage units of
`
`
`a given batch, as well as batch-to-batch differences, are re­
`Fig 90-1. Tablet press operators checking batch record
`
`
`
`duced to a minimum through proper in-process controls and
`in confor·
`mance with Current Good Man ufactur ing Practices (courtesy,
`
`
`
`good manufacturing practices. The recognition of the im­
`Lilly).
`
`
`
`portance of validation both for equipment and processes has
`
`
`
`
`ability of a clinically effective formulation but also on the raw
`
`
`
`greatly enhanced assurance in the reproducibility of formu­
`It is in these areas that significant
`lations.
`progress has been
`
`
`
`
`materials, facilities, personnel, validated processes and
`
`
`
`equipment, packaging, and the controls used during and after
`
`
`
`of a made with the realization that large-scale production
`
`preparation (Fig 90-1).
`
`
`satisfactory tablet or capsule depends not only on the avail-
`
`Tablets
`
`ministration. Compression equipment continues to improve
`
`
`
`
`
`
`
`Tablets may be defined as solid pharmaceutical dosage
`both as to production
`
`
`
`forms containing drug substances with or without suitable
`
`speed and the Ul}iformity of tablets
`
`
`
`diluents and prepared either by compression or molding
`
`
`
`compressed. Recent advances in tablet technology have been
`use since the latter
`reviewed.2-5
`
`methods. They have been in widespread
`are more frequently
`
`
`
`part of the 19th century and their popularity continues. The
`Although
`tablets
`
`discoid in shape, they
`term compressed tablet is believed
`
`
`
`also may be round, oval, oblong, cylindrical, or triangular.
`to have been first used by
`
`
`
`They may differ greatly in size and weight depending on the
`
`
`John Wyeth and Brother of Philadelphia. During this same
`
`
`
`amount of drug substance present and the intended method
`
`period molded tablels were inLroduced to be used as "hypo­
`
`
`
`of administration. They are divided into two general classes,
`
`
`dermic" tablets for the extemporaneous preparaUon of solu­
`as a dosage form
`
`
`
`whether they are made by compression or molding. Com­
`tions for injection. Tablets remain popular
`
`because
`
`
`
`
`
`pressed tablets are usually prepared by large·scale production
`
`of the advantages afforded both to t.he manufacturer
`(eg, simplicity
`
`
`
`und economy of preparation, stability, and
`
`
`methods while molded tablets generally involve
`small-scale
`
`
`
`convenience in packaging, shipping, and dispensing) and the
`
`
`
`operations. The various tablet types and abbreviations used
`
`
`
`
`Patient (eg, accuracy of dosage, compactness, portability,
`
`
`in referring to them are listed below.
`blandness
`
`of taste, and ease of administration).
`Compressed Tablets (CT)
`Although
`
`
`the basic mechanical approach for their manu­
`and contain no special coating.
`has under­
`
`facture has remained the same, tablet technology
`
`
`These tablets are formed by compression
`or granular
`
`
`
`gone great improvement Efforts are wntinually being made
`They are made from powdered,
`
`
`crystalline, materials, alone
`or in combination with binders,
`to understand
`
`
`
`disintegrants, lubricants, diluents, and
`
`
`more clearly the physical characteristics of
`
`in many cases, colorants.
`
`Tablets (SCT)-These are compressed con­
`
`
`
`
`tablet compression and the factors affecting the availability
`tablets
`taining a sugar coating. Such coatings may he co lored and are beneficial
`Sugar-Coated
`
`of tbe drug substance from the dosage form after oral ad-
`1603
`
`

`
`1804· CHAPTER 90
`
`in covering up drug substances possessing objectionable tastes or odors,
`
`
`to indicate that they are not to be swallowed. Examples of these tablets
`
`
`
`
`and in protecting materials sensitive to oxidation.
`
`
`are Hala7.one Tablets for Solution and Potassium Permanganate Tablets
`for Solution.
`
`
`Film-Coated Tablets (FCT)-'l'hese are compressed tablets which
`
`Effervescent Tablets-In addition to the drug substance, these con­
`
`are covered with a thin layer or film of a water-soluble material. A number
`
`and an organic acid such as tartaric or citric. I11
`
`
`
`of polymeric substances with film-forming properties may be used. Film
`tain sodium bicarbonate
`the presence of water, these additives react liberating carbon dioxide which
`
`coating imparts the same general characteristics as sugar coating with the
`
`
`
`added advantage of a greatly reduced time period required for the coating
`
`
`acts as a distintegrator and produces effervescence. Except for small
`operation.
`
`
`
`quantities of lubricants present, effervescent tablets are soluble.
`Tablets (ECT)-These are compressed tablets coated
`Enteric-Coated
`
`Compressed Suppositories or Inserts-Occasionally vaginal sup­
`
`
`
`with substances that resist solution in gastric fluid but disintegrate in the
`
`
`
`positories, such as Metronidazole Tablets, are prepared by compression.
`
`
`
`intestine. Enteric coatings can be used for tablets containing drug sub·
`Tablets for this use usually contain lactose as the diluent. In this case,
`or destroyed in the stomach, for those which
`as well as for any tablet intended for administration
`stances which are inactivated
`other than by swal­
`t.he manner in which it is to be used.
`
`irritate the mucosa, or as a means of delayed release of the medication.
`lowing, the label must indicate
`Multiple Compressed Tablets (MCT)-These are
`Tablets- These are small, flat,
`
`compressed tablets
`Buccal and Sublingual
`oval tablets:
`
`Tablets intended for buccal administration by inserting into the buccal •
`cycle.
`made by more than one compression
`
`
`Dayered Tablets-Such tablets are prepared by compressing
`additional
`
`
`
`pouch dissolve or erode slowly, therefore they are formulated and com­
`pressure to give a hard tablot.
`
`tablet granulation on a previously compressed granulation. The operation
`
`
`
`pressed with sufficient
`Progesterone
`
`may be repeated to produce multilayered tablets of two or three layers.
`
`
`
`tablets, Tablets may be administered in this way. Sublingual such as those
`
`Special tablet presses are required to make layered tablets such as the
`
`
`
`containing nitroglycerin, isoproterenol hydrochloride, or erythrityl
`Versa press (Stokes-Pennwalt).
`
`
`tetranitrate, are placed nnder the tongue. Sublingnal tablets dissolve
`
`Press-Coated Tablets-Such tablets,
`are
`also referred to as dry-coated,
`
`
`
`this form of ad­rapidly and the drug substances are readily absorbed by
`
`
`
`
`prepared by feeding previously compressed tablets into a special tablt!tin�:
`machine and compressing another granula tion layer around the preformed
`ministration.
`They have all the advantages
`Molded Tablets or Tablet Triturates (TT)
`tablets.
`
`
`of compressed tablets, ie, slotting,
`
`monogramming, speed of disintegration, etc, while retaining the attributes
`
`
`
`Tablet triturates are usually made from moist material using a triturate
`
`of sugar-coated tablets in masking the taste of the drug substance in the
`
`core tablets. An example of a press-coated tablet pTess is the Manesty
`
`
`
`mold which gives them the shape of cut sections of a cylinder. Such tablets
`Drycota. Preaa-coated tablets can also be used to acporotc incompatible
`must be completely and rapidly soluble. The problem arising from
`they can provide a means to give an enteric
`
`
`compression of these tablets is the failure to find a lubricant that is com­
`
`
`
`drug substances; in addition,
`pletely water-soluble.
`
`
`coating to the core tablets. Both types of multiple-compressed tablets
`
`Dispensing Tablets (DT)-These tablets provide a convenient
`
`have been widely used in the design of prolonged-action dosage forms.
`of potent drug that can be incorporated readily into powders and
`Controlled-Release
`can be form ulated
`quantity
`
`Tablets-Compressed tablets
`
`to re lease the drug substance i n a manner to provide medication
`liquids,
`
`
`thus circumventing the necessity to weigh small quantities. These
`over a
`
`
`tablets are supplied primarily as a convenience for extemporaneous
`period of time. There are a number of types which include delayed-action
`compounding and should never be dispensed
`as a dosage form.
`
`
`
`tablets in which the release of the drug substance is prevented for an in­
`terval of time after administration
`
`Hypodermic Tablets (HT)-Hypodermic tablets are soft, readily
`or until certain physiological conditions
`
`
`soluble tablets and were originally used for the preparation of solutions
`
`exist; repeat-action tablets which periodically release a complete dose of
`solutions are now available for most
`
`
`the drug substance to the gastrointestinal fluids; and the extended-Telease
`to be injected. Since stable parenteral
`there is no justification
`drug subetances,
`
`for the use of hypodermic tablets
`
`
`
`or sustained-release tablets which continuously release increments of the
`
`
`for injection. Their use in this manner should be discouraged since the
`
`
`
`contained drug sub�tance to the gastrointestinal fluids. These tablets
`are discussed in Chapter 92.
`
`
`
`resulting solut.ions are not sterile. Large quantities of these tablets con­
`tablets to be used for preparing
`
`tinue to he made but for oral administration. No hypodermic tablets have
`Tablets for Solution-Compressed
`to solutions must be labeled
`
`
`ever been recognized by the official compendia.
`
`
`solutions or imparting given characteristics
`
`
`
`
`
`Compressed Tablets ( CT)
`
`In order for medicinal substances, with or without diluent.�,
`
`
`and is subsequently ejected from the die. The weight of the
`
`
`to be made into solid dosage forms with pressure, using
`
`tablet is determined by the volume of the material which fills
`
`
`
`
`available equipment, it is necessary that the material, either
`
`
`
`the die cavity. Therefore, the ability of the granulation to
`flow freely into the die is important
`an uniform fill,
`
`
`in crystalline or powdered form, possess a number of physical
`in insuring
`
`
`as well as the continuous movement of the granulation from
`
`
`
`characteristics. These characteristics include the ability to
`
`
`
`flow freely, cohesiveness, and lubrication. Since most ma­
`the source of supply or feed hopper. If the tablet granulation
`
`
`terials have none or only some of these properties, methods
`
`
`the tablet after com­does not possess cohesive properties,
`
`
`of tablet formulation and preparation have been developed
`
`pression will crumble and fall apart on handling. As the
`to the material
`
`
`to impart these desirable characteristics which
`
`punches must move freely within the die and the tablet m'ust
`
`
`be readily ejected from the punch faces, the materiltlmust
`is to be com pre58e d into tablets.
`The basic mechanical unit in all tablet-compression
`
`
`
`have a degree of lubrication to minimize friction and to allow
`
`equipment includes a lower punch which fits into a die from
`
`for the removal of the compressed tablets.
`
`the bottom and an upper punch, having a head of the same
`There are three general methods of tablet preparation:
`(1)
`
`shape and dimensions, which enters the die cavity from the
`
`method; the wet-granulation method; (2) the dry-granulation
`
`
`
`
`top after the tableting material fills the die cavity. See Fig
`
`
`and and (3) direct compression. The method of preparation
`90-2. The tablet is formed by pressure applied on
`the punches
`
`
`
`the tablet in order to give the added ingredients are selected
`
`
`
`
`formulation the desirable physical characteristics allowing
`
`the rapid compression of tablets.
`After compression the
`
`
`
`
`tablets must have a number of additional attributes such as
`
`
`appearance, hardness, disintegration ability, appropriate
`
`
`characteristics, and uniformity which are also
`dissolution
`
`influenced both by the method of preparation and by the
`
`
`
`added materials present in the formulation. In the prepa­
`
`
`ration of compressed tablets the formulator must also be
`
`
`cognizant of the effect which the ingredients and methods of
`
`
`
`preparation may have on the availability of the .active ingre­
`
`
`dients and hence the therapeutic efficacy of the dosage form.
`
`
`
`In response to a request by physicians to change a dicumarol
`tablet in order that it might be more easily broken, a Canadian
`
`company reformulated to make a large tablet with a score.
`lower punch,
`
`
`Subsequent use of the tablet containing the same amount of
`
`Fig 90-2. Basic mechanical unit for tab let compression:
`
`die, and upper punch (courtesy, Vector/Colton).
`
`

`
`•
`
`•
`
`s
`)
`I,
`l
`11
`e . t
`.t
`N
`.) l;
`
`d
`lt
`g
`te
`lS
`;e 10
`
`te
`'1·
`)e
`of
`e·
`n.
`ol
`Ill
`·e.
`of
`
`ORAL SOLID DOSAGE FORMS 1605
`
`lhot wuler-soluble diluonl.ll he
`
`
`solubility, it iR recommended
`drug substance as the previous tablet, resulted in complaints
`
`
`
`
`used to avoid possible biouvullability problem:;. Highly ad­
`
`that larger-than-usual doses were needed to produce the same
`sorbent subi>Lanccs, �-��. hcntonile and kaolin, arc to l.x: vvoideJ
`therapeutic
`
`
`response. On the other hand, literature reports
`
`
`
`indicate that the reformulation of a commercial digoxin tablet
`
`
`in making tablets of drugs used clinically in small dosage, such
`
`
`
`resulted in a tablet, although containing the same quantity
`
`as the cardiac glycosides, alkaloids, and the synthetic estro­
`
`
`clinical of drug substance, that gave the desired
`
`gens. These drug substances may be adt�orbcd lo the point
`
`response at
`aflcr nd mini11l r:ttiun.
`
`where they are not completely available
`
`
`that can be half its original dose. Methods and principles
`of amine bases with Inclose, ur amine salts
`The combination
`
`
`
`
`used to assess the effects of excipients and additives on drug
`
`
`with lactose in the presence of an alkaline lubricant, results
`
`
`absorption have been reviewed.6,? See Chapters 38, 76, and
`in tablets which discolor on aging.
`77.
`
`
`
`Microcrystalline cellulose (Avice!) is usually used as an
`
`
`excipient in direct compression formulas. However, its
`Tablet Ingredients
`
`
`
`presence in 5-15% concel)trations in wet granulations has been
`
`
`shown to be beneficial in the granulation and drying processes
`In addition to the active or therapeutic ingredient, tablets
`
`
`
`
`
`in minimizing case-hardening of the tablets and in reducing
`
`contain a number of inert materials. The latter are known
`tablet mottling.
`
`
`
`according They may be classified as additives or excipients.
`
`
`to the part they play in the finished tablet. The first group
`those which help to impart satisfactory
`Binders
`contains
`processing
`lo th� furmulvtion.
`to the powdered
`and comprt>..ssion chnmcterL<>t.ics
`rl'he�>e
`
`Agents used to impart cohesive qualities
`to as binders or granulators.
`include (1) dilucnts, (2) binders,
`
`material are referred
`They Im­
`and (3) glidont.'>
`nnd Jubri
`cants. The second group of SHided substances .belps t.n give
`
`
`
`part a cohesiveness to the tablet formulation which insures
`
`phys ical characteristit.'fl lo lh� finbhed
`
`
`the tablet remaining intact after compression, as well as im­
`additional
`de!!irahle
`are (1) disintegrants, (2) colors,
`
`
`
`
`proving the free-flowing qualities hy the formulation of
`
`tablet. Included in this group
`
`
`granules of desi:rcd lmn.lnes.'l nnd size. Materials commonly
`
`and (4) and in the case of chewable tablets, (3) flavors,
`
`used as binders include slarch,
`
`gelntin, and sugars as sucrose,
`
`sweetening agents.
`
`
`
`
`glucose, dextrose, molasses, and lactose. Natural and syn­
`Although the term inert has been applied to these added
`
`thetic gums which have been used include acacia, sodium al­
`
`
`materials, it is becoming increasingly apparent that there is
`
`
`ginate, extract of Irish moss, pan war gum, ghatti gum, muci­
`
`
`
`
`of t.he ex­between lho properties an important relationship
`
`lage of isapol husks, carboxymethylcellulose, methylcellulose,
`
`
`cipients and the dosage forms containing thorn. Preformu­
`Veegum, and larch arabogalactan.
`
`
`lation studies demonstrate their influence on HtnbWty, bio­
`polyvinylpyrrolidone,
`Ol.her a,gonts which rnay hi' considered
`
`binders under Gertain
`availabilit.y,lllld the processes by which the dosage forms ure
`are polyethylene
`
`
`glycol, ethylcellulose, waxes,
`
`
`
`prepared. 'T'he need for acqtLiring more informAtion and use
`circumstances
`for axcipients
`in a joint venture
`hM been rocognized
`water, and alcohol.
`sl�md1lrds
`The quantity of binder used has considerable influence on
`
`
`
`
`of the Academy of Pharmaceutical Sciences and the Council
`
`
`the characteristics of the compressed tablets. The use of too
`
`
`of the Pharmaceutical Society of Great Britain. The program
`much binder or too strong a binder will make a hard tablet
`
`
`is called the Codex of Pharmaceutical Excipient Project and
`
`which will not disintegrate easily and which will cause exces­
`
`
`
`
`the Academy's Industrial Pharmaceutical Technology Section
`
`
`sive wear of punches and dies. Differences in binders used
`
`
`has undertaken its organization and implementation.
`
`
`
`for CT Tolbutamide resulted in differences in hypoglycemic
`which have 1111
`
`effects ,observed
`Materials
`r-uhel!ive
`clinically.
`Diluents
`of their own will require o stmnger
`qualities
`hinder l.lt<Ul those
`Frequently the single dose of the active ingredient is small
`
`
`
`with these qualities. Alcohol and water arc not hinders in the
`
`
`and an inert substance is added to increase the bulk in order
`
`
`true sense of the word; but because of their solvent action on
`
`
`to make the tablet a practical size for compression. Com­
`
`
`
`
`8<lme ingredients �;uch as lactose, starch, and cell uloses, they
`
`
`
`per pressed tablets of dexamethasone contain 0. 75 mg steroid
`
`
`chtlnge U1e powdered muleti:)l to granules and the residual
`moisture rrtaim.'tl enables the materials
`
`
`
`tablet, hence it is obvious that another material must be added
`to adhere together
`.
`to make tablet.ing
`Diluents used for
`possible.
`this purpose
`when compressed
`
`
`
`
`include dicalcium phosphate, calcium sulfate, lactose, cellu­
`
`Binders are used both as a solution and in a dry form de­
`
`
`
`
`lose, kaolin, mannitol, sodium chloride, dry starch, and pow­
`
`
`pending on the other ingredients in the formulation and the
`
`dered sugar. Certain diluents, such as mannitol, lactose,
`
`method of preparation. The same amount of binder in so­
`
`
`
`sorbitol, sucrose, and inositol, when present in sufficient
`
`
`lution will be more effective than if it. were dispersed in a dry
`
`
`quantity, can impart properties to some compressed tablets
`
`
`form and moistened with the solvent. By the latter procedure
`nttenL is not as effective
`U1e binding
`in reaching ond welling
`
`that permit disintegration in the mouth by chewing. Such
`each of �he purticlt>s wil hin llte Mlll.'IS of J>�lw dcn;. fi'x"'ch uf U1e
`
`tablets are commonly called chewable
`Upon chewing,
`tablets.
`
`iu a powder blend hn.s a coat.iug uf adsorbed nir on
`
`
`properly prepared tablets will disintegrate smoothly at a
`pari iclc.-.
`its surface, and it is this film whiub must lw J>eu elrnlf•d hci'CJrc
`
`
`satisfactory rate, have a pleasant taste and feel, and leave no
`lhe powdcrtl can be wetted by lhc bindar soluLion.
`
`
`
`unpleasant aftertaste in the mouth. Diluents used as excip­
`Sittce
`powders differ with respect to lho unsc with which Lhcy cnn
`
`
`ients for direct compression formulas have been subjected
`to
`w hll'(ll'pomte !.he binding ngeu.t in
`he wetted, it i8 prcfcmhlc
`
`
`prior processing to give them flowability and compressibility.
`solutinn. By thilll.cchnique it i.s ofte11 possible to gain crfcc
`
`These are discussed under Direct Compression, p 1613.
`
`tivc binding wil.h a lnwer concenlrat ion of binder. lL should
`
`
`Most tablet formulators tend to use consistently only one
`be 11nted thaL lherfl ar<' �;rvnriJl
`
`"flrcgclutinized" sturches
`
`
`
`or two diluents selected from the above group in their tablet
`
`
`formulations. Usually these have been selected on the basis
`
`available which are intended to be added in the dry form so
`
`
`of experience and cost factors. However, in the formulation
`
`
`that water alone can be used as the granulating solution.
`
`
`of new therapeutic agents the compatibility of the diluent with
`
`
`
`The direct compression method for preparing tablets (see
`
`
`the drug must be considered. For example, calcium salts used
`
`
`
`page 1613) requires a material that not only is free-flowing but
`
`
`
`as diluents for the broad-spectrum antibiotic tetracycline have
`
`
`also sufficiently cohesive to act as a binder. This use has been
`
`
`been shown to interfere with the drug's absorption from the
`
`
`
`described for a number of materials including microcrystalline
`
`
`gastrointestinal tract. When drug substances have low water
`
`
`
`cellulose, microcrystalline dextrose, amylose, and polyvinyl-
`
`1
`
`

`
`1606 CHAPTER 90
`
`It has been postulated
`pyrrolidone.
`that microcrystalline
`The method of adding a lubricant to a granulation is irn.
`
`
`
`is to perform its function
`
`
`cellulose is a special form of rellulosc fihril an whjch lhe indi­
`
`
`
`portant if the material
`satisfactorily
`should be finely divided by pasflin!( it through
`
`by hydrogen vidual crystallites are held together largely
`
`The lubricant
`a 60-to 100-mesh nylon cloth onto the granulation.
`
`
`
`bonding. The disintegration of lnblctM containing lhe rellu
`In pro­
`
`
`lose occurs by breaking the intercrystallite bonds by the dis­
`
`duction this is called "bolting" the lul>ricant..
`After adding
`
`integrating medium.
`
`
`the lubricant the granulation is tumhled or mixed genl.ly to
`Starch Paste-C orn starch is widely used as
`
`
`
`
`distribute the lubricant without coaling lhc particles t-oo wen
`a binder. The
`may vary from 10 to 20%. It is usually
`concentration
`prepared
`
`
`or breaking them down lo finer particles.
`
`
`at; it it; to be used by dispersing corn starch in sufficient cold
`Prolonged blending ol' lubricant. with a granulation can
`
`
`
`
`to make a 10% w/w solution
`time and dis­
`purified water
`and warming in a
`
`
`mat.erinlly affect the hardness. disintegraliun
`
`for thr result.anllablet.ll. The quantity
`
`solul.ion performance
`
`
`water bath with continuous stirring until a translucent paste
`v1mes, being as low us 0.1%, and in some cases us
`forms.
`of lubricant
`used as a 10-200'o
`high as 5%. LubricanUI have been added to the g�anulating
`Gelatin Solution-Gelatin is generally
`agents in the f<1rn) uf suspensions
`
`or emulsions .. 'Phis tech­
`
`
`solution; gelatin solutions should be freshly prepared as
`needed and used while warm or they will solidify. The
`nique serves to reducu t.he number of operational
`gelatin
`procedure
`s
`
`
`is added to cold purified water and allowed to stand until it
`and thus reduce the processing
`time.
`It is then warmed in water bath to dissolve the
`is hydrated.
`must be given to proper ut.lention ln selecting a lubricant,
`
`
`
`is made up to the final volume
`
`ilc; compatibility with the drug agent. Perhaps the most
`
`gelatin and the solution
`on a
`tales
`
`
`widely iuvestjgat.ed drug i11 acetylsalicylic acid. Different
`weight basis to give the concentration desired.
`a 25-50% solution
`
`
`Lhe stability of uspirin. Talc with a hjgh
`Glucose Solution-Generally
`is used.
`voried significantly
`wa.c1 associated with
`
`Glucose does not dry out well and is therefore not suitable
`C-l!lcium content and a high loss on ignition
`
`aspirin decom
`increased
`
`
`position. From a slnbility standpoint,
`
`
`where the tablets are subject to humid conditions. These
`
`are not true 25 and 50% solutions
`for combination
`solutions
`since the corn
`
`the relative accept.ability of ta.hleL lubricants
`
`80% solida.
`
`with aspirin was found to decrease in
`
`
`syrup contains only approximately To prepare
`the following order:
`acid, laic, and aluminum
`oil, stearic
`
`the binder solution, lhe corn syrup is weighed and dissolved
`hydTogenated vegetable
`water is added lo give
`
`in purified water. Sufficient purified
`
`stearate.
`desired on a weight basil!. If clarification
`the concentration
`The primary problem in the preparation of a water-soluble
`
`
`
`
`is desirable, it can be strained through cloth.
`
`
`
`tablet is the selection of a satisfactory lubricant. Soluble
`to be effective
`
`This is insoluble in water. It is used ef­
`
`
`lubricants reported include sodium benzoate,
`Ethylcellulose-
`
`a mixture of sodium benzoate and sodium acetate,
`
`
`
`
`fectively as a binder when dissolved in alcohol, or as a dry
`sodium
`and Corbowax 4000. However,
`chlclride,
`
`
`binder in a granulation which is then wetted with alcohol. As
`leucine,
`it has been
`used as a 5% solution. It is
`a binder in solution it is usually
`
`
`suggeRted that formulations used to prepare
`water-soluble
`
`
`widely used as a binder for moisture-sensitive materials. To
`
`tablets may represent. a number of compromises between
`
`
`com[>ression efficiency and water solubility.
`
`
`make the solution, ethylcellulose is dissolved in anhydrous
`
`While maJ.'DC·
`
`
`denatured alcohol and made up to the final volume on a weight
`
`
`sium stearate is one of the most widely ·used lubricunls, its
`basis.
`
`
`
`hydrophobic propert.ies can retard disintegration and disso­
`can be used as an aqueous or
`PVP-Polyvinylpyrrolidone
`
`lution. To overcome these waterproofing characteristics
`
`
`
`
`an alcoholic solution and this versatility has increased its
`
`
`
`�>Odium lauryl sulfate is sometimes included. One compound
`range from 2% and vary consid­
`
`popularity. Concentrations
`
`
`round to have the lubricating properties of magnesium stea·
`erably.
`
`rate without its disadvantages is magnesium Iaury! sulfate.
`
`It will be noted that binder solutions are usually made up
`
`Its safety for usc in pharmaceuticals has not yet been estab·
`to weight rather than volume. This is to enable the formu­
`lished.
`
`lator to determine the weight of the solids which have been
`Glidants
`added to the tablet granulation
`
`in the binding solution. This
`
`becomes part of the total weight of the granulation and must
`
`A glidant is a substance which improves bhe IJow charac­
`
`
`
`
`be taken into consideration in determining the weight of the
`
`
`teristics of a powder mixture. These materials are always
`dry state just prior t4J compre$Sion (ie, during the
`
`
`
`
`compressed tablet which will contain the stated amount of the
`added in the
`(Cabot);
`
`therapeutic agent.
`
`
`
`
`lubrication step). Colloidal silicon dioxide [Cab-o-sil
`
`Quso (Phi/a Quartz) I is the most commonly used glidant
`and
`l-u bricq n t.�
`of 1% or lcSl!. Talc
`is generally
`used in low c�mcentrations
`is also used and may se rve the dual purpose
`{asbestos-free)
`
`Lubricants have a number of functions in lahlcl manufac­
`as lubricant/glidant.
`
`
`ture. They prt>venl adhesion of the tablet material to the
`surface ()f' the dies and punches,
`
`reduce interparticle fri<�tilln,
`Disintegrants
`lbc ejection of Lhe tablets from lhe die cavity, and
`facililate
`may improve the rate of now of the table! granulat.i()o.
`
`
`A disintegrant is a substance, or a mixture of substances,
`include talc, magnes ium stearate,
`it.<; breaJcup or disintegration
`Commonly used lubricanl.li
`added to a tablet to facilitate
`oi Is.
`
`calcium ::;tea ral.e, stearic acid, and hyd rogenat.ed
`
`Mler admini�lration. '!'he activ('
`must bo relensed
`vegctabl.e
`io�redicnt
`<'<>ll·
`us possible to allow for
`Most lubricants with the exception of talc are used in
`
`J'mm tile tablet matrix as effiricnlly
`les.<! I han l'il. W hen used alone, talc may require
`tenlrations
`its rapid dissolution.
`have
`
`Muterial�-> serving as <lillinLegrants
`as hir,h t�s 5%. I .uhricanls ore in mm�t cases
`a] gins,
`
`
`
`been rhem irally clas!1ified as starches, clays,
`ccmccnlrations
`<:ell uloses,
`
`
`
`materials. Poor selection or excessive amounts
`
`gums, and crosslinked polymers.
`hydrophobic
`The oldrsL and slill the mo:;l popular du;integront:; are rorn
`
`
`
`cun re:�ult in "watcrpmo£ing'' the tablets, resulting in poM
`and p<lLato star ch which have been well-dried
`and p<>wdered.
`
`
`tahleL disint.egrat ion and dissolution of the drug substance.
`is highly desirable if
`for watrr unci swelL'> when mois
`
`The addition of lhc proper lubricant
`Starch has a great Affinity
`tends to stick lo the punches and
`the materialtu he tahleted
`
`tened, thull facilitating the ruptUl'c of the tablet. matrix.
`lhnl its disint.egraLing A
`I Juwever, others have suggested
`ction
`dies. Immediately after compre.'lsion nwsllablel.s have the
`
`lo expand and will hlnd and :!tick to the side of the
`tendency
`
`
`
`in tabJeU; ill due lo capillary action rather thru1 swelling; the
`shape of' Lhe st.a rch grains increatH!S lh� porosity
`
`die. The choice oft he proper lubrica nt will effectively elVer­
`of
`spherkal
`rome this.
`5%, is
`
`
`the tablet, thus promot.ing capillary a<·tion. Starc·h,
`
`

`
`ORAL SOLID DOSAGE FORMS 1807
`
`
`suggested, lmt if mure rapid disintegrut.ion is desired, this
`preparation, as well as serving as a means of identification to
`
`
`amount may be increased to 10 \lr 15%. Anhough it might be
`the user. The wide diversity
`in the use of colors in solid dos­
`age forms makes it possible to use color as an important cat­
`
`expected that disintegralinn Lime would decrease as the per­
`
`
`egory in the identification code developed by the AMA to
`
`centage of starch in t.he tnblet increased, this does not appear
`
`to be the case for LolbuLamide tablets. In this instance, there
`
`
`establish the identity of an unknown compressed tablet in
`
`siluation!l arising frum poisoning.
`
`appears to be a critical starch concentration for different
`
`
`
`
`granulations of the chemical. When Lheir disintegral,ion ef­
`All colorants used in t