The Interrelationship of Bulk Density, Granule Density

University of Rhode Island
[email protected]
Open Access Master's Theses 1967
The Interrelationship of Bulk Density, Granule Density, Tablet Weight, and Weight Variation
Amritkumar Bhandari University of Rhode Island
Follow this and additional works at: https://digitalcommons.uri.edu/theses Recommended Citation Bhandari, Amritkumar, "The Interrelationship of Bulk Density, Granule Density, Tablet Weight, and Weight Variation" (1967). Open Access Master's Theses. Paper 180. https://digitalcommons.uri.edu/theses/180 This Thesis is brought to you for free and open access by [email protected] It has been accepted for inclusion in Open Access Master's Theses by an authorized administrator of [email protected] For more information, please contact [email protected]

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THE l Tlml:iELA.TIONSHIP OP BULK DE:l IT ,
GR.1'.NULE D.tiNSITY, TABLET. fEIGH~ ,
fD WEIGHT VARIATION BY
.AMRITKlfllAR BRAND 'P.I
A TUE 'IS UBMITTEl) I FAHTIAL FULFILLME T 0 . · r B
REQUI. ~L,TB FOR THE DEGREE OF
1' I.'> TER O:t' $C!EBC
IN
PllABMACY
UNIVEl.SITY or.i EliOD'.E liJLAlID
1967

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ABSTRACT

The effects of granule density and bulk density on tablet weight, weight variation, and tablet density were determined for tablets compressed on a Colton Model 216, rotary ta.blet press. Hardnsss, thickness, and disintegration times were also determined for the tablets produced. Standardized granulations were ma.de from lactose and mixtures of lactose and bismuth subcarbonate, with gelatin as a binder. Granule density and bulk density of the granulations were varied by changing the concentrations of bismuth aubcarbonate in the formula. All tablets were made at a fixed rate of tableting using standardized settings of the fill, pressure, and overload adjustments. The interrelationship between granule density and bulk density was found to be almost linear, as was also the relationship between granule density, bulk density, and tablet weight.

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OF
.A.MRITKUMAR BHAND.Al I
Approved: Thesia Committee:
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UlUVERSITY Ol' RliODE lSLAltD
1967

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l'ilLE OF CONTEUTS

I.

INTHODUCTIOli

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PA Glti
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. . . II. REVIEW OF PREVIOUS LITERATURE • • • • • • • • •

III. EXPERIMENT.AL FROCEDUBE • • • • • •

.. • • • 12

General Order of Experiments • .. • .. • • • • • 12

Preliminary Experiments to Teat Applicebilit7

. . . . of Literature 1;ata •
. . . . . . . . . . . . . . Granulation . .

.. • • • • • • • 13
13

Prepa,ratton O·f Starch Solution • • • • • • • l";

. . . . . . . . . . . . . Preparation of Granules • • • • • • • • • • 14

Lubrieation ..

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1 :5

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Tablet Compression • • • • • • • • • • • • • 15

Granule Size Experiments • o • • • • • • • • 15

Tablettns Rate Experiments • • • • • • • • • 16

Compre11sion of 16 Mesb Granules • • • • .. • 16

Compreasion of 20 Meeb Effect of Die Size • •

Granules • •• • •

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.• • ..

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16 17

Granule and Bulk Denatt7 Experiments • • • • • 17

Preparation of Granules • • • • • • • • • • 17
Method of Variation of Density of Granules • 18

Preparation of tbe Binder Solution • • • • • 18

·Mixing • • • • • • • • • • • • • • • • • • • 18

Granulation.

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Separation Into Sise Fractions • • • • • • • 20

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CHAPTER

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Determination of tbe Pertinent Character-

istics of the Granulations • • • • . •

20

Size Distribution Determination • • •

20

Bulk Density Determination ••

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21

Granule Density Determination •••.•• 21

Compression of Granules . . • • • . • • • • 23

Equipment • . . • • •

• • • .

23

Selection of Operating Para.meters • • • . 23

Lubrication • • . . • • . • • • • . • • . 23

Determination of Tablet Characteriatics

24

. Weight . . . . . . • . . . . .

. . . 24

. . Size • •

• • •• • • • • • • • • e• •

24

. . . . . . . . . . . . . . Hardness • •

.

24

Dis i ntegration Time • • • • • • • • • • • 25

. . . . . . . . IV. RESULTS AND DISCUSSION

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. . . . . . . . . Preliminary Experiments

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. . . Granule Chara.cteris t ics

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. . . . . . . . Effect of Granule Si ze

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. . . . Effect of Tableting Size

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. . . . . . . . Effect of Die Diameter •

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Interrelationship cf Gra.nule Density , Bulk

Density, Tablet Weight and Weight

. . . . . . . . . . . . . . . Variation

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. . . . . Characteristics of Granulations

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TABLE OF C ON~ENT S

CHJ_PTEH

Size Distribution • • • • • • • • • . .

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Bulk Density • • • • • • • • , • • • • • • 36

. . . . . Granule Density •

• • • • •

36

. . . Miscellaneous • • •

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Relationship of Bulk Density to Granule Density 41

Interrelation8hipB of Tablet Weight, Granule

DenE;i ty, Bulk Density and Weight Va.ria.tion

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Characteristics of ·t;he Tablets Produced from

. . . . . . the Different Granulations . .

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49

. . . . v. ( SUMMARY Alill CONCLUSIONS • • • • • • • 53

. . . . . . . . . . . . . . . . . . . . . . REFERE11CES

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LIST OF TABLES

TABLE

PAGE

I. Granulation Formulas • • • • • • . . . . . • • 19

II. Tablet Weight and Coefficient of Variation Ob-

. . . . . . . . . . . tained From 3 Different Sizes of Gra.:nula-

tions

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27

III. Average Weight of Tablets irom No. 16 and No.

. . . . . . . 20 Sieve Granules, Ubta.ined at Different

Speeds • • • • • •

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. . . . . . IV. Effect of Die Size - Average Weight and Co-

efficient of Variance of Tablets

34

. . . . . . . . . . . . . . . . I
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V. Plain Lactose Granulation #16 Mesh Diameter

Count

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VI. Granulation of Lactose and Bismuth SubCarbon-

ate Particle ::Jiameter Count

. . . . . . 39

. . . . . . . . . . . . VII. Granule and Bulk Density of Different Gran-

ulations . • • • .

,.

40

IDI. Effects of Granule and Bulk Density on

Tablet Weight and Weight Variation •

45

IX. Table Showing Other ~ata on Tablets P.toduced • 52

LIST OF FIGURES

FIGURE

PAGE

. 1. Mercury Displacement Apparatus to Determine Granule Density •••••••• • • • • •

. • • 22

2. Effect of Tableting Rate on the Average Weight

of Tablets from No. 16 and No. 20 Sieve

Granulations • • • • • • • • • • • • • • • • • 31 3. Effect of Ta.bleting Rate on Average Weight of

Tablets from No. 16 and No. 20 Sieve Granules • 32

4. Granule Size Distribution of Plain Lactose No.

16 Size Granules • • • • • • • • • • • • • • • 37

5. Granule Size Distributions of Lactose - Bismuth

Subearbonate No. 16 Granules • • • • • • • e • 38

6. The Relationship of Bismuth Subcarbonate

Concentration to Granule Density • • • • • • • 44

7. Effect of Granule Density on Average Weight of
Tablets • • • . • • • • . • • • • • • • . • • • 47
8. Effeot of Bulk 1)ensity on Average Weight of
Tablets • • . • . • • • . • • • • • • • • " • • 48
9. Relationship Between Granule Density and Bulk

Density .. • • • • • • • • • • • • • • • • • • • 50

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INTRODUCTION
The compressed tablet has become one of the most widely accepted dosage forms for the administration of orally effective therapeutic agents. It provides a convenient and, if well made, an efficient form of solid dosage for ore.l administration. The advantages of this type of pharmaceutical preparation are well known and include accuracy of dose, economy, stability, portability, concentration, elegance, and convenience in dispensing and shipping.
The invention of compressed tablets is usually attributed to Brackedon, who in 1843 obtained an English patent on a simple device for compressing dry powders. By 1674 tablets for almost every known disease were being sold on European and American markets. At one time the preparation of tablets was based more on empirical considerations than on sound scientific principles. In recent years, however, there bas been a trend to move from the 'art' in ma.king tablets toward the science of tableting.
Tablets first became official in the gtn revision of the United States Pharmacope1a, 1926, and have been offtcial in each succeeding revision.
The National ]'ormular:t has included an increasing