1 Chapter 4 TABLETS 2007.1.22 P38. 2 Introduction - The definition of tablets Tablets are (compressed, slab-shaped × ) solid dosage forms consisting of

1

Chapter 4 TABLETS

2007.1.22

P38

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Introduction - The definition of tablets

Tablets are (compressed, slab-shaped×) solid dosage forms consisting of active ingredient(s) and suitable pharmaceutical excipients. They may vary in size, shape, weight, hardness, thickness, disintegration and dissolution characteristics, and in other aspects. They may be classed, according to the method of manufacture, as compressed tablets or molded tablets.

Caplets and boluses

Administration route of tablets: orally, sublingually, buccally, vaginally

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Introduction – Two common methods for tablets preparation

compressed tablets: (primarily) are manufactured with tablet machine

molded tablets: (a limited number) prepared on a large-scale by tablet machinery or on a small-scale by manually forcing dampened powder material into a mold

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Introduction – Advantages of tablets for oral administration

1. conveniently carried2. readily identified3. easily taken4. prescribing flexibility5. Efficiently and productively manufactured6. Packaged and shipped at lower cost and with less

breakage7. More stable and have a longer shelf-life8. Tablets are sometimes used as the source of a

medicinal agent when it is not otherwise available.

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Types of tablets

1) Compressed tablets (压制片 CT)

2) Multiple compressed tablets (多层压制片MCT)

3) Sugar-coated tablets (糖衣片 SCT)

4) Film-coated tablets (薄膜衣片 FCT)

5) Gelatin-coated tablets (明胶包衣片 )

6) Enteric-coated tablets (肠溶衣片 ECT)

7) Buccal or sublingual tablets (口腔用片与舌下片 )

8) Chewable tablets (咀嚼片 )

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Types of tablets 9) Effervescent tablets(泡腾片 )

10) Molded tablets (模制片MT)

11) Tablet triturates (模印片 TT)

12) Hypodermic tablets (皮下片 HT)

13) Dispensing tablets (配方片、调剂片 DT)

14) Immediate release tablets (速释片 IR)

15) Instant disintegrating/dissolving tablets (速崩 /溶片 )

16) Extended release tablets (缓释片 ER)

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Types of tablets—— Compressed tablets (CT)

Composition: medicinal agent(s) / active ingredient / API / TAI pharmaceutical adjuncts/adjuvants/excipients

diluents or fillers:

binders or adhesives:

wetting agents:

disintegrants or disintegrating agents:

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Types of tablets—— Compressed tablets (CT)(continued)

glidants, antiadherents, lubricants(lubricating agents): enhance the flow of the tableting material, prevent the sticking of fill material to the punches and dies and produce tablets having a sheen, reduce friction between the tablet and the die wall (minimize wear of the punches and dies, improve hardness distribution)

助流剂：能改善颗粒表面粗糙性 ( 减少颗粒间摩擦力 ) ，增加颗粒流动性的辅料，作用：使能顺利流入模孔，片重差异合格。

抗黏着剂：能减轻颗粒对冲模黏附性（最大静摩擦力）的辅料，作用：防止压片物料黏着于冲模表面，保证冲面光洁度。

润滑剂：能降低颗粒（或片剂）与冲模孔壁之间摩擦力，改善力的传递和分布的辅料，作用：增加颗粒的滑动性，使填充良好、片剂的密度分布均匀，保证推出片剂的完整性。

miscellaneous adjuncts: colorants, flavorants

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Types of tablets——Multiple compressed tablets (MCT)

prepared by subjecting the fill material to more than a single compression.

1) multiple-layered tablet

The reason to choose this form:

2) tablet-within-a-tablet

Special machines are required.Tablet-within-a-tablet

Double-layered-tablet

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Types of tablets —— sugar-coated tablets (SCT)The purpose: 1) protecting the enclosed drug from the

environment, 2) provides a barrier to objectionable tasting or

smelling drugs, 3) enhances the appearance of the CT and 4) permits the imprinting of identifying

manufacturer’s information.

Disadvantages: time, expertise, larger (50%), heavier and more shipping cost

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Types of tablets —— film-coated tablets (FCT)

FCTs are compressed tablets coated with a thin layer of polymer capable of forming a skin-like film over the tablet.

The realization of targeted drug release

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Types of tablets —— gelatin-coated tablets

A recent innovation —— GELCAPS——a capsule-shaped gelatin-coated compressed tablet

Advantages:

a) one-third smaller than a capsule filled with an equivalent amount of powder (less bulky)

b) facilitates swallowing

c) more tamper-evident

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Types of tablets —— enteric-coated tablets (ECT) provide delayed-release features

ECTs are designed to pass unchanged through the stom

ach with transit to the intestines.

Scope of application:

a. Drug substance is destroyed by gastric acid.

b. Drug substance is irritating to the gastric mucosa.

c. By-pass of the stomach enhances drug absorption.

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Types of tablets —— buccal or sublingual tablets

Buccal or sublingual tablets are flat or oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue for absorption through the oral mucosa (sublingual tablets).

Scope of application: the drugs intended for the local effect in the buccal ca

vity (buccal tablets) the drugs that are destroyed by the gastric juice and/o

r are poorly absorbed from the GI tract (sublingual tablets)

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Types of tablets —— buccal or sublingual tablets(continued)

Buccal tablets are designed to erode slowly, while sublingual tablets are designed to dissolve promptly and provide rapid drug effects.

Lozenges (锭剂 ,糖锭 ) or troches (compressed lozenges含片 ,含锭 ,糖锭Molded lozenges are sometimes referred to as pastilles.):.

being slowly dissolved —— usually for localized effects

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Types of tablets —— chewable tablets Chewable tablets, which have a smooth, rapid

disintegration when chewed or allowed to dissolve in the mouth.


the administration of tablets of large-size to children and adults.

e.g. nutrition supplementary dosage form (calcium and vitamins )

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Types of tablets —— effervescent tablets

Effervescent tablets are prepared by compressing granular effervescent salts that release gas when in contact with water.


water-soluble medicinal substances

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Types of tablets —— molded tablets (MT, 模制片 ) Molded tablets, as tablet triturates, may be

prepared by molding rather than by compression. Molded tablets are prepared by forcing dampened powders under low pressure into die cavities.

The resultant tablets are very soft, soluble, and are designed for rapid dissolution.

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Types of tablets —— tablet triturates (TT) ( 模印片 , 研制片剂 ) Tablet triturates are small, usually cylindrical, molded (MTT) o

r compressed tablets (CTT) containing small amounts of usually potent drugs.

Features: a. Only a few tablet triturates are available today, with most of t

hese TTs produced by tablet compression. The few TTs which remain are used sublingually, as nitroglycerin tablets.

b. A minimal amount of pressure is applied during their manufacture. (intended to be readily and completely soluble in water)

c. A combination of sucrose and lactose is usually the diluent. d. In the past, TTs were employed in compounding procedures to

provide accurate amounts of potent drug substances.

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Types of tablets —— hypodermic tablets (HT) ( 皮下注射片 )

no longer available HT (one type of dispensing tablets, molded tablets and ta

blet triturates) were originally used by physicians in the extemporaneous preparation of parenteral solutions. The required number of tablets was dissolved in a suitable vehicle, sterility attained, and the injection performed.

Advantages: convenience, individualized Disadvantages: the difficulty in achieving sterility

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Types of tablets —— dispensing tablets (DT) ( 调剂片，配方片 ) no longer in use DTs might better have been termed compounding tablets

because they were used by the pharmacist in compounding prescription and were not dispensed as such to the patient.

to provide premeasured accurate amounts of potent drug substances for compounding multiple dosage units

DTs had the dangerous potential of being inadvertently dispensed as such to patient.

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Types of tablets —— immediate release tablets (IR)

Immediate release tablets are designed to disintegrate and release their medication absent of any special rate-controlling features as special coatings and other techniques.

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Types of tablets —— instant disintegrating / dissolving tablets (IR)

Instant-release tablets are characterized by disintegrating/dissolving in the mouth within one minutes; some within 10 seconds.

Tablets of this type are designed for patients (including pediatric and geriatric patients) who have difficulty in swallowing tablets.

After placing them on the tongue they liquefy and the patient swallows the liquid.

Techniques used: lyophilization (Zydis); soft direct compression (WOW-Tab)

Water-soluble excipients are used to wick water into the tablet for rapid disintegration/dissolution.

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Types of tablets —— extended release tablets (ER)

Extended-release tablets / controlled release tablets are designed to release their medication in a predetermined manner over an extended period of time.

Expressions such as ``prolonged-action,'' ``repeat-action,'' and ``sustained-release'' have also been used to describe such dosage forms. However, the term ``extended-release'' is used for Pharmacopeial purposes.

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Types of tablets —— vaginal tablets

Vaginal tablets are uncoated and bullet- or ovoid-shaped tablets which are inserted into the vagina for localized effects.

Scope of application: antibacterials or antifungals

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CTs —— quality standards and compendial requirements

The apparent physical features of compressed tablets: 1) shape: round, oblong, unique 2) thickness: thick or thin

3) diameter: large or small 4) flat or convex

5) unscored or scored in halves, thirds and quadrants

6) engraved or imprinted with an identifying symbol and/or code number

7) coated or uncoated 8)colored or uncolored 9) number of layer.

The die (模圈 ) and punches (冲 ) determine the physical features of compressed tablets.

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CTs —— quality standards and compendial requirements

Other physical specifications and quality standards:

tablet weight weight variation

content uniformity tablet thickness

tablet hardness tablet disintegration

drug dissolution in-process controls verification after the production

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quality standards and compendial requirements —— tablet weight and Chp weight variation The quantity of fill placed in the die cavity of a tablet press

determines the weight of the resulting tablet. Chp weight variation: sample amount 20 tablets Tablets should comply with the following requirements sta

ted in the table below.

Average weight Weight variation limit

Less than 0.3 g ± 7.5%

0.3 g or more ± 5%

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quality standards and compendial requirements —— tablet weight and Chp weight variation the procedure of weight variation determination in Chp:

Weigh accurately 20 tablets and calculate the average weight, then weigh individually each of the 20 tablets. Compare the weight of each tablet with the labelled tablet (if no labelled weight is stated, compare the weight of each tablet with the average weight calculated). No more than 2 of the individual weights exceed the weight variation limit stated in the table above and none doubles the limit.

Sugar, film and enteric coated tablets

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quality standards and compendial requirements —— content uniformity

applys to potent drug of low dose. USP method, 10 tablets are individually assayed for their c

ontent.

The amount of active ingredient in each tablet lies within the range of 85% to 115% of the label claim(标示量 ) and the RSD is less than 6.0%.

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quality standards and compendial requirements —— tablet thickness

Tablet thickness is determined by the following four factors:

1) the diameter of die 2) the amount of fill permitted to enter the die 3) the compactability of the fill material 4) the force or pressure applied during compression The tableting press affects not only tablet thickness but al

so tablet hardness. Tablet thickness may be measured by hand gauge (手持标准尺 ) or automated equipment.

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quality standards and compendial requirements —— tablet hardness and friability ( 脆碎度 )

Tablet hardness 1)The greater the pressure applied, the harder the tab

lets. 2) The hardness required by different tablets a) lozenges and buccal tablets: hard (dissolve slowl

y) b) the tablets for immediate drug release: soft 3) measurement a) special dedicated hardness testers b) multifunctional equipment

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quality standards and compendial requirements —— tablet hardness and friability ( 脆碎度 )(continued)

Friability 1) It is used to determine a tablet’s durability 2) Method: allowing the tablets to roll and fall within th

e rotating apparatus (friabilator); determine the loss in weight;

3) requirement: weight loss ≤1%

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quality standards and compendial requirements —— tablet disintegration

1) The significance of tablet disintergration

2) Testing apparatus

3) Procedure

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quality standards and compendial requirements —— tablet disintegration (continued)

4) Complete disintegration

5) Requirements for different tablets

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quality standards and compendial requirements —— tablet disintegration (continued)

The disintegration of enteric-coated tablets:

1) to be tested in simulated gastric fluid (SGF) for one hour after which no sign of disintegration, cracking, or softening must be seen.

2) to be tested in simulated intestinal fluid (SIF) for the time (usually, 1 h) stated in the individual monograph

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quality standards and compendial requirements —— tablet dissolution( 溶出度 )

1) The importance of in vitro dissolution test a) to guide the formulation and product development

process toward product optimization

b) to monitor the performance of manufacturing process

c) to assure bioequivalence from batch to batch

d) as a requirement for regulatory approval for product marketing for products registered with the FDA and regulatory agencies of other countries.

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quality standards and compendial requirements —— tablet dissolution (continued)

2) The goal of in vitro dissolution is to provide a reasonable prediction of the product’s in vivo bioavailability.

Basis: The combinations of a drug’s solubility and its intestinal permeability are supposed as a basis for predicting the likelihood of achieving a successful in vivo – in vitro correlation (IVIVC).

Considered are drugs determined to have: a) high solubility and high permeability (IVIVC may be expected.) b) low solubility and high permeability (IVIVC may be expected.)

c) high solubility and low permeability d) low solubility and low permeability

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3) The formulation and manufacturing factors affecting the dissolution of a tablet

a) the particle size of the drug substance b) the solubility and hygroscopicity of the formulation c) the type and concentration of the disintegrant, bin

der, and lubricant used d) the manufacturing method, particularly, the comp

actness of the granulation and the compression force

e) the in-process (加工过程中的 ) variables

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4) Apparatus 1 and 2 in USP

a) are used principally for immediate release solid dosage forms

b) consist of a variable speed ① stirrer motor, ② a cylindrical stainless steel basket on a stirrer shaft (apparatus 1) or a paddle as the stirring element (apparatus 2), ③ a 1000-ml vessel of glass fitted with a cover having a center port for the shaft of the stirrer, and three additional ports, two for the removal of samples, one for the placement of a thermometer, and a suitable ④ water bath to maintain the temperature of the dissolution medium in the vessel.

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5) Test method a) A volume of the dissolution medium is placed in the

vessel and allowed to come to 37 ±0.5 .℃ ℃ b) The stirrer is rotate at the specified speed. c) At stated intervals, samples of the medium are

withdrawn for chemical analysis6) Requirement for rate of dissolution The specific required rates of dissolution are different for

tablets containing different medicinal agents. e.g. not less than 85% of the labeled amount is dissolved

in 30 minutes

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7) Inconsistencies in dissolution

occur not between dosage units from the same production batch, but rather between batches or between products from different manufacturers.

Pooled dissolution testing has emerged. This process recognizes the concept of batch characteristics and allows pooled specimens to be tested.

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Compressed tablet manufacture

•The classification of manufacturing methods

wet granulation: drugs that are stable to moisture and heat

dry granulation: drugs that are sensitive to moisture and heat

powder ～ : drugs that are sensitive to moisture and heat, fill material possessing good flowability and compressibility

crystal ～： drug with proper crystal form and good flowability

granulation( 制粒法 )

direct compression( 直接压片法 )

The requirements for fill material for tablet making

1) flowability ( 流动性 , free-flowing from the hopper into the dies)

2) compressibility ( 可压性 )

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a widely employed method The action of granulaiton 1) to provide free-flowing quality 2) to improve powder compressibility by increasing material

density 3) to reduce dust in the air

Compressed tablet manufacture—— wet granulation

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The steps of wet granulationweighing and blending the ingredients(称量与混合 )

preparing a damp mass(制软材 )

screening the damp mass into pellets or granules

drying the granulation(颗粒干燥 )

sizing the granulation by dry screening(过筛整粒 )

adding lubricant and blending(加润滑剂，混合 )

tableting by compression (压片 )

(liquid binder)

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Weighing and blending (to be continued) 1) active ingredient, diluent/filler, disintegrant 2) The definition of fillers Among the fillers used are lactose, microcrystalline cellulose, starch, powdered sucros

e, and calcium phosphate a) The choice is based on the material features, its relative

cost, and its compatibility with the other formulation ingredients.

b) calcium salts —— tetracycline antibiotics (×) c) lactose —— primary or secondary amine (×) d) Microcrystalline cellulose has good compactability, comp

atibility, consistent uniformity of supply.

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Weighing and blending (continued) 3) The definition of disintegrants (disintegrating agents) Two characters: water absorbing, swelling. They include: starches, 5% to 10% suitable, 20% exerts a rapid disintegration; dried. carboxymethyl starch sodium(CMS-Na, 羧甲基淀粉钠 ); primojel sodium starch glycolate (羟基乙酸淀粉钠 ), 5%, swell up to 300% of it

s volume; microcrystalline cellulose(MCC, 微晶纤维素 ) croscarmellose sodium(CCNa, 交联羧甲基纤维素钠 ), 2%; Low-Substituted Hydroxypropyl Cellulose(L-HPC, 低取代羟丙基纤维素 )

crospovidone(CPVP, 交联聚维酮 );4) the method of disintegrants addition (internal, external, internal-

external)

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Definition of disintegrantsDisintegrants are the materials that swell or expand on e

xposure to moisture and effect the rupture or breakup of the tablet in the GI tract.

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The steps of wet granulationweighing and blending the ingredients(disintegrant)

preparing a damp mass

screening the damp mass into pellets or granules

drying the granulation

sizing the granulation by dry screening

adding lubricant and disintegrant, and blending

tableting by compression

(liquid binder)Internal( 内加法 )

External( 外加法)

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Preparing the damp mass (制软材 )

1) A binder is added to the powder mixture to facilitate the adhesion of the powder particles.

2) Among the binding agents used are povidone, an aqueous preparation of corn starch (10-20%), glucose solution (25-50%), molasses(糖浆 ), methylcellulose (3%), carboxymethylcellulose, and microcrystalline cellulose.

3) The proper amount of binding agents to be used press a portion of the mass in the palm into a ball, the ball crumbles under mo

derate pressure. (be compactible by squeezing in the hand) over-wetting can result in granules that are too hard for proper tableting and under-wetting can result in tablets that are too soft and tend to crumble.

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Wet screening——Screening the damp mass into pellets or granules The screen is usually No. 6- to 20-mesh. The resultant granules are spread evenly on large pieces of paper. Drying the granulation (under controlled time, temperature and

humidity) Sizing the granulation by dry screening being passed through a screen of a smaller mesh than that used to

prepare the original granulation The choosing of granule size (Voids left by too large a granulation

would result in uneven tablets.) a) smaller tablets: screens from 12- to 20-mesh size b) normal tablets: screens from 6- to 20-mesh size

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Compressed tablet manufacture—— wet granulation Adding lubricants and blending 1) The method of addition Lubricant is dusted over the spread-out granulation through a fine mesh screen. 2) The actions of lubricants a) to improve the flow of the granulation in the hopper to the die cavity b) to prevent the adhesion of the tablet formulation to the punches an

d dies during compression (to give a sheen to the finished tablet) c) to reduce friction between the tablet and the die wall during the tabl

et’s ejection from the tablet machine3) the commonly used lubricants magnesium stearate, calcium stearate, fumed silicon dioxide (气相二氧化硅 ), stearic acid, talc, sodium stearyl fumarate (硬脂富马酸钠 ) the commonly used quantity: 0.1% to 5%

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Compressed tablet manufacture—— All-in-one granulation methods

equipment: fluid-bed granulator or microwave vacuum processing method

The fluid-bed granulator performs the following steps; 1) preblending the formulation powder, including active ing

redients, fillers, and disintegrants 2) granulating the mixture by spraying onto the fluidized po

wder bed, a suitable liquid binder, as an aqueous solution of acacia (阿拉伯胶 ), hydroxypropyl cellulose, or povidone

3) drying the granulated product to the desired moisture content.

4) adding lubricants and tableting

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Compressed tablet manufacture—— Dry granulation apply to materials that cannot be prepared by wet granulation due to th

eir degradation by moisture or by the elevated temperatures required for drying the granules

Two methods are used. 1) slugging (压片法 ) a) weighing and mixing the ingredients b) slugging or compressing the powder mixture into large flat tablets or p

ellets of about 1 inch in diameter c) breaking up the slugs by hand or by a mill d) sizing with a screen of desired mesh e) preparing tablets after adding disintegrants/lubricants 2) roller compaction (滚压法 ) b) pressing the powder mixture between high-pressure rollers at 1 ton to

6 tons of pressure often preferred over slugging; binding agents: MC or HMC 6 to 12%

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The classification of tablet presses( 压片机的分类 )

Tablet presses

single-punch presses（单冲压片机） multi-station rotary presses（旋转式多冲压片机）

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A picture of a single-punch press

Single-punch tablet press

electric motor

manual driving wheel

cylindrical gearing

belt gearing

hopper

feed shoe

cam gearing

core components

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The main components of single-punch tablet presses

Core components: die (模圈 )

lower punch (下冲 )

upper punch (上冲 ) The action of each components

hopper

feed shoe

lower punch

die

upper punch

tablet weight adjustor

tablet ejector adjustor

tablet hardness adjustor

Schematic diagram of the main components of single-punch press

die cavity

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The basic mechanical process of tableting with single-punch presses

a) filling materialb) scraping away the

excessive granulationc) forming a tablet by

compressiond) pushing up the tablet to

stage surfacee) shoving the tablet aside

upper punch

dielower punch

tablet

fill material

a)

b)

c)

d)

e)

a)

The compression process on a single punch machine in cross-section

冲压机

60ZP19 rotary tablet press

A picture of multi-station rotary press

upper turret (上冲固定台面 )

die table (模圈固定台面 )

lower turret (下冲固定台面 )

head: upper turret, lower turret, die table

hopper (饲料斗 )

feed-frame (饲料框架 )

16, 19, 27, 33, 37, 41, 49 stations

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The core components and compression cycle of rotary presses

A: upper punchB: die cavityC: dieD: lower punch

tablet ejectionfilling and adjustment compression

track of upper punch

track of lower punch

feed-frame

③wipe-off blade

②weight control cam

⑤upper compression roll

④lower compression roll⑧ejector knob

①pull-down cam

⑥upper punch raising cam

⑦lower punch raising cam

⑨sweep-off blade

The compression cycle of a rotary tablet press

The compression is applied by both the upper punch and the lower punch.

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Compressed tablet manufacture—— Tableting of granulation

Multiple-layered tablets are produced by the multiple feed and multiple compression of fill material within a single die.

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Compressed tablet manufacture—— Direct compression tableting Suitable for

1) granular chemicals possessing free flowing and cohesive properties

e.g. potassium chloride

2) chemicals added with special pharmaceutical excipients which impart the necessary qualities for the production of tablets by direct compression

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Compressed tablet manufacture—— Direct compression tableting

The direct compression tableting excipients include:

a) fillers, as spray-dried lactose, microcrystals of alpha-monohydrate lactose, sucrose-invert sugar – corn starch mixtures, microcrystalline cellulose, crystalline maltose麦芽糖 , and dicalcium phosphate;

d) disintegrants, as direct-compression starch, sodium carboxymethyl starch, cross-linked carboxymethylcellulose fiber, and cross-linked polyvinylpyrrolidone;

c) lubricants, as magnesium stearate and talc;

d) glidants, fumed silicon dioxide

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Compressed tablet manufacture—— Direct compression tableting

The reasons for capping, splitting or laminating of tablets

1) air entrapment

2) not immaculately cleaned or not perfectly smoothed punches

3) too great a proportion of fine powder

4) Tablets have aged or have been stored improperly

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Compressed tablet manufacture——tablet dedusting

to remove traces of loose powder adhering to tablets following compression.

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Tablet coating

The reasons for tablet coating

1) to protect the medicinal agent against destructive exposure to air and/or humidity;

2) to mask the taste of the drug;

3) to provide special characteristics of drug release;

4) to provide aesthetics or distinction to the product;

5) to prevent inadvertent contact by nonpatients with the drug substance

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Tablet coating

The general methods involved in coating tablets are as follows

1) sugarcoating tablets

2) film-coating tablets

3) enteric coating

4) pan coating

5) fluid-bed or air suspension coating

6) compression coating

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Tablet coating —— sugarcoating tablets

The sugarcoating of tablets may be divided into the following steps:

1) waterproofing and sealing (if needed)(隔离层 )

2) subcoating(粉衣层 )

3) smoothing and final rounding(糖衣层 )

4) finishing and coloring (if desired)(色衣层 )

5) polishing(打光 )

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The equipment and method for sugarcoating coating pans of galvanized iron, stainless steel, or copper; The pans operate at about a 40°angle. The pan is rotated at

moderate speeds, allowing the tablets to tumble over each other while making contact with the coating solutions which are gently sprayed onto the tablets. To allow gradual build-up of the coatings, the solutions are added in portions, with warm air blown in to hasten drying. Each coat applied only after the previous coat has dried.

Tablets should be thin-edged and highly convex to allow the coatings to form rounded rather than angular edges.

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1) waterproofing and sealing (if needed) (隔离层 )

aim: to prevent the components from being adversely affected by moisture; one or more coats; shellac (虫胶 ), zein (玉米朊 ruan), or a polymer as cellulose acetate phthalate

2) Subcoating(粉衣层 )

aim: to bond the sugar coating to the tablet and provide rounding

a) 3 to 5 subcoats of a sugar-based syrup are applied. The sucrose and water syrup also contains gelatin, acacia, or PVP. b) When the tablets are partially dry they are sprinkled with a dusting powder, usually a mixture of powdered sugar and starch but sometimes talc, acacia, or precipitated chalk as well. c) Then drying the tablets. Repetition (15 to 18 times) the subcoating process until the tablets are of the desired shape and size.

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3) smoothing and final rounding(糖衣层 ) aim: to complete the rounding and smooth the coatings

5 to 10 additional coatings of a thick syrup; This syrup is sucrose-based with or without additional components as starch and calcium carbonate.

4) finishing and coloring(色衣层 )

aim: to attain final smoothness and the appropriate color

several coats of a thin syrup containing the desired colorant

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5) imprinting(印刷 ) aim: to impart identification codes and other distinctive symb

ols to the product The imprint may be debossed, embossed, engraved, or printe

d on the surface with ink. 6) polishing(打光 ) aim: to render the tablets the desired sheen/gloss/luster a) pans lined with canvas cloth impregnated with carnauba

wax(巴西棕榈 ) and/or beeswax b) Pieces of wax may be placed in a polishing pan c) light-spraying of the tablets with wax dissolved in a nonaq

ueous solvent

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Tablet coating —— film-coating tablets

1) The disadvantages of sugarcoating process a) time-consuming b) requiring the expertise of highly skilled technicians c) doubling the size and weight of the original uncoated tablets d) may vary in size from batch to batch and within a batch e) large tablets are not as easily swallowed as are small tablets.2) The advantages of film-coating process a) coated tablets having essentially the same weight, shape, and size as

the originally compressed tablet b) The coating is thin enough to reveal any identifying monograms. c) far more resistant to destruction by abrasion than are sugar-coated

tablets d) the coating may be colored to make the tablets attractive and

distinctive.

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3) The components of nonaqueous film-coating solutions: a) film former: e.g. CAP b) alloying substance: to provide water solubility or permeability to t

he film e.g. PEG c) plasticizer: to render flexibility and elasticity to the coating e.g. c

astor oil d) surfactant: to enhance spreadability of the film e.g. polyoxyethyl

ene sorbitan derivatives e) opaquants and colorants: e.g. titanium dioxide, FD&C or D&C d

yes f) sweeteners, flavors, and aromas: saccharin糖精 , vanillin香草醛 g) glossant: beeswax h) volatile solvent: alcohol-acetone mixture

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#1: the expense of the volatile solvents and the environmental problem of the release of solvents

#2: The problem is the slow evaporation of water. e.g. AQUACOAT (FMC Corporation) contains a 30% ethyl cellulose pseudo

latex with a high solids content and low viscosity.4) The components of a typical aqueous film-coating solutions: a) film-forming polymer (7-18%): e.g. cellulose ether polymers as HPMC, H

PC and MC b) plasticizer (0.5-2.0%): e.g. glycerin, propylene glycol, PEG, diethyl phthal

ate, and dibutyl subacetate c) colorant and opacifier (2.5-8%): FD&C or D&C lakes and iron oxide pigm

ents d) water

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5) Some problems with aqueous film-coating a) picking and peeling( 碎片粘连和剥落 ) the appearance of small amounts or large amounts of film fragments

flaking from the tablet surface b) orange peel effect( 起皱、“橘皮”样粗糙面 ) roughness of the tablet surface due to failure of

spray droplets to coalesce (愈合、融合、老化 ) c) mottling(色斑 ) an uneven distribution of color on the tablet surface d) bridging(桥接 ) filling-in of the score-line or indented logo on the tablet by the film e) tablet erosion(片心磨损 ) disfiguration of the core tablet

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Tablet coating —— enteric coating

1) Enteric coated solid dosage forms are intended pass through the stomach intact to disintegrate and release their drug-content for absorption along the intestines.

2) The rationale(设计原理 ) a) transit time b) thickness of the coatings c) Usually, an enteric coating is based on factors of pH, resisting dissoluti

on in the highly acid environment of the stomach but yielding to the less acid environment of the intestine.

3) Flexibility: a) whole tablets or granules and particles; b) thick or thin; c) aqueous-based or organic-solvent-based coating systems

4) Among the materials used in enteric coatings are: pharmaceutical shellac, hydroxypropyl methylcellulose phthalate (HPMC

P), polyvinyl acetate phthalate, diethyl phthalate, and cellulose acetate phthalate(CAP)

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Tablet coating —— fluid-bed or air suspension coating

1) The application of fluid bed processing equipment

a) spray coating for powders, granules, beads, pellets or tablets

b) preparing tablet granulations

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2) Different types of fluidized bed system a) the bottom-spray method (底喷型，Wurster process)

a vertical cylinder; warm air blasts released in the chamber; suitable for batches of small amount

is particularly recommended for taste masking, enteric release, and barrier film

b) the top-spray method (顶喷型 )

suitable for batches of large amount

is recommended for sustained-release and enteric-release products

c) the tangential-spray method (切线喷型 )

used in rotary fluid-bed coater

is recommended for layering coatings, and for sustained-release and enteric- coated products

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3) control variables a) equipment used

b) the method of spraying (e.g. top, bottom, tangential)

c) spray-nozzle distance from spraying bed

d) spray droplet size

e) spray rate

f) spray pressure

g) volume of fluidization air

h) batch size

i) methods and time for drying

j) air temperature and moisture content in processing compartment

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Tablet coating —— compression coating

1) in a manner similar to the preparation of multiple compressed tablets of tablet-within-a-tablet

2) is an anhydrous operation and thus may be safely employed in the coating of tablets containing a drug that is labile to moisture.

3) Compared to sugarcoating using pans, compression coating is more uniform and uses less coating materials.

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Impact of manufacturing changes on solid dosage forms

1) the changes in formulation and the changes in the method of manufacture

2) The changes in formulation could involve:

a) the use of starting raw materials, including both the active ingredient and pharmaceutical excipients

b) the use of different pharmaceutical excipients

c) the use of different quantities of the same excipients in a formulation

d) the addition of a new excipient to a formulation

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Impact of manufacturing changes on solid dosage forms

3) The changes in the method of manufacture could involve:

a) use of processing of manufacturing equipment of a different design

b) a change in the steps or order in the process or method of manufacture

c) different in-process controls, quality tests, or assay methods

d) production of different batch sizes

e) employment of different product reprocessing procedures

f) employment of a different manufacture site

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Packaging and storing tablets

1) Tablets are stored in tight containers, in places of low humidity, and protected from extremes in temperature.

2) Products that are prone to decomposition by moisture generally are copackaged with a desiccant packet.

3) Drugs that are adversely affected by light are packaged in light-resistant containers.

4) The hardness of certain tablets (including tablets containing aluminum hydroxide, sodium salicylate, phenylbutazone) may change upon aging usually resulting in a decreased disintegration and dissolution rates

5) Certain tablets containing volatile drugs, as nitroglycerin, should be preserved in tight containers, preferably of glass, at controlled room temperature.

6) A woman should not handle finasteride tablets because it has the potential to adversely affect a male fetus.

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Oral administration of solid dosage forms

1) Taking solid dosage forms with adequate amounts of water is important.

The dangers caused by taking tablets or capsules without water are:

a) the dosage form’s lodging in the esophagus,

b) esophageal ulceration.

Among the drugs of greatest concern in this regard are:

alendronate sodium, aspirin, ferrous sulfate, any nonsteroidal antiinflammatory drug (NSAID), potassium chloride and tetracycline antibiotics.

2) Patients who suffer from gastroesophageal reflux disease

3) The relation between oral medication and meals

4) Oral dosage forms that have special coatings

5) The use of crushed tablets or opened capsules

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Other solid dosage forms for oral administration

1) lozenges

often used as buccal tablet; can be made by compression or molding;

have a special place in the delivery of medication to buccal cavity in the treatment of oropharyngeal candidiasis, cough/cold symptoms and minor sore throat

2) Pills

Pills are small, round, solid dosage forms containing a medicinal agent and intended to be administered orally.

Documents

1 Chapter 4 TABLETS 2007.1.22 P38. 2 Introduction - The definition of tablets Tablets are (compressed, slab-shaped × ) solid dosage forms consisting of