Lucrare de curs nr.

6 con(inutului la Tema: ,rsubstanle furmucetttice uuuiliare folosite formulare& "cipsutelor operculste cu cedure prelungitd"

1.

este

condiJionarea in capsule operculate cu cedare prelungita dupa formulele de mai jos' care Descrieli etapele fluxului tehnolojic de fabricare a capsulelor din prescrip{ie. tndicalii terapeutice. Parlicularitali de eliberare

2. 3. Metodele de

Substanlele auxiliare folosite ta fnrniularea medicamentelor prelungita Principiile de selectare a substan{elor auxiliare.

Blen,

in

capsule

cu cedare
pentru

oblinere

microgranulelor. microcapsulelor,

peietelor

rolul flecd*ri component din

farmacii. 2.
1"
Diclofenac Sustainecl-Release Capstties Diltiazem Hydrocloride Extended-Release capsules

,, l' ;"r!-

go tlirough the 28 mesh are taken uncoated granules A. The iormulation uncoated granules A is as follows:
Component
Diclof'errac: sodilt tn

ils
CI

'ilre granules are spray-coated with 1263 g of a coating liqurd iiaviiig iii' fciici"ir;q

% by weight
43.1 I 1.0

cornpositii.rn according to a conventionai methocl to produce long-acting granules' The weight of the coat was about 8% of the weisht of the uncoated granules'
Component
Ethylcellulose

Citric acid
Cornstarch

% by weight
2.1
0.c)

1t.0
32.9 1.4

Purified sllcrose
HydroxyProPYl cellulose Total

Polyvinyl PYnolidone K30

Talc

r00.0

0.2 96.2 100.0

Ethyl alcohoi

e.

Alternate method
granules:

of

preparing uncoated
o.

Total

i: ii.

1000 g of diclofenac sodium, 30 g of fumaric acid, and 170 gof cornstarch at'e mixed and Pulverized' The fine powders thus produced are processed to produce spherii;al granuies' using 600 g of purified sucrose that is

Prepalation
rnethod:

of long-acting

granules' altentate

a. b.

(r00 g o1'uncoated granule-s B are placed irlto a coating apparatus with fluidizecl bed' The granules are spray-coated with 1667 g

obtained by shifting through a 20-28 mesh as a core, while spraying a solution of 25 g of hydroxypropyl cellr:lose in
115 g of ethYl alcohol'

o1 a coating liquid having the following cornposition according to a conventional rnethod to produce long-acting gratrules'

(c, 2004

by CRC Press LLCI

Diclofenac Sustained'Release Capsules

Bill of Materials
Scale (mg/Cap)

Material Name
Diclofenac. USE Diclofenac Sodium Pellets i520 mg/g)

Qty/l000 Caps (g)

MANUFACTURINC DIRECTIONS 1. Fill at relative humidity that does not 457c and a temperature of 20-25"C.
2.

ul. The granules are then dried 55"C.

lv.

for 3 h

at

exceed

These dried granules are then passed thror-rgh ii 1.1 rnesh followed by oassage
through a 28 mesh. The grar-rules that do not go through the 28 mesh are taken as uncoated granules. The formurlation o1' this uncoated granuies B was as lbllows:

Calculate exact amount based on quantity of actirc insreclient itt uncoated beads' Frll i9l.-< Irg bascd on l00ci potencv ba.sis.
Prcparation ot' uncoated gratrules:

i.r.

ol'tliclof'eniic sodium. 200 -s of citric acid, and 200 g of cornstarch are rnixed and
3(X) g

Component Diclofenac sodium Fumaric acid

Cornstarch

% by weight
54.8
1.6

pulverized,

b. The fine powders

thus prepared are pro-

cessed to produce spherical grahules, using

c. d. These dried

600 g of purified sucrose that was obtained b1' shifting through 20-28 mesh as a core, rvhile spraying a solution of 25 g of hydroxypropyl cellulose rn 4-/5 g of ethyl alcohol' The granules are then dried for 3 h at 55'C'

9.3 32.9
1.4

Purified sucrose Flydroxypropyl cellulose

Total

r00.i)

granules are then passed through a 14 mesh, followed by passage

fhrough a 28 rnesh. The granules that do not

5.

gil through the 28 mesh are taken its uncoated granules A. The ibrmulation ct
uncoated granules

Preparation of lor-rg-acting granules: a. 600 g of uncoated granules A ar"e placed into a coating apparatus v"ith a fluidized bed' b. '-ilre granules tlre spray-coated with 1263 g of a coai.ing iir-1ul.ci iruvirrg ii," fc;ii;''"iri:I

A is as follows:
% by weight
+-). /

cornposition according to a conventionai rnethocl to produce long-acting granules' The weight of the coat was about 8% o['the
weight of thc uncoated granules.
Component
Ethylcellulose

Component
Diclof'enac sodir-ttlr

Citnc acid
Cornstarch

I 1.0 11.0 32.9

1.4

% by weight
2.1 K-30 0.9 0.2 96.2

Purified sLlcrose Hydroxypropyl cellulose

Total

Polyvinyl pynolidone
.n.l^
I (tll

100.0

Ethyl alcohol

e.

Alternate method
granules:

of

preparing uncoated
6.

Total

r00.t)

i. ii.

1000 g of diclofenac sodium, 30 g of fumaric acid, and 110 gof cornstarch are mixed and Pulverized' The fine powders thus produced are processed to produce spherii--al granules'

Preparatiotl
rnethod:

of long-actir-rg

granules. alterlrate

a. b.

(r00 g 01'uncoated granr-rle s B are placed irltcl a coating apparatus with fluidized bed.

600 g of purified sucrose that is obtained by shifting through a 20-28 mesh as a core. while spraying a solution of 25 g of hydroxypropyl cellulose in 475 g of ethyl alcohol.
r.rsing

The granules are spray-coaied with 1667 g o1 a coating liquid having the l'ollowing

composition according to a cour,'etrtional method to produce lorlg-acting granules'

(!) 2004 by CRC Press LLC

Diltiazem Hydrochloride Extended-Release Capsules

Diltiazern hydrochloride is a calcium ion cellular influx inhibitor (slow channel biocker). The extended-release capsules ccrntain diltiazem hvdrochloride in extended-relcasc beacls at dose-s

Fonmuln

-l

of i1,0. 1 80. 2'10, 300. 360.

Diltiazem hydrochloride
Lactose

I 120.00 g

irrc. Ther ulstl cotttain.: tttiet'rrct'\ \ti.tlline e fo\c \tearate. Eudragit. por idorre. talc. tttnsttc*iuttl \teltlate, hydroxypropyl methylcellulose, titiiniunl dioridc'. polysorbate, simethicone, gelatin, FD&C Blue No. 1, FD&C Red No, 40, D&C Red No. 28, FD&C Green No, 3. biack iron oxide. and other solids. In another fornrulation. the 120 rng. 180 mg, 240 mg,
anci 300 nrg capsLrles also

and 420 eellulose. su-

119.00 g
101 )

Microcrystalline cellulose (Avicel pH

Povidone K30

140.00 g

2l .00

After introducins the Foii clers it-tto a planetary mixer and granulating \ante throLrgh the obtaineci plastic, tnass is extrudcd through a cylinder with 1 mm diameter holes
(.\lexanderwork). The small cylinders are rounded, so as to obtain beads, by means of a spheronrzet. After drying at 60'C for'12 h, the beads are sifted and the fiaction with size comprised between 0.7 mm and 1.4 mm are retained. 1,179 g of beads were obtained yield {84a/n1.

contain: black iron oxide, ethyl-

cc'llulose
\Ller'()\L-.

. FD&C

BlLrc' No. 1. l'un.iaric acid, -uelatin. sta|ch. talc. titaniurl dioxide. ilhite wax, and

othc'r ingredients. The 360 tn-e capsule also contains: black

rron oxide. diethyl phthalate. FD&C Blue No. I, gelatin, por idone K17. sodium lauryl sulfate, starch, sucrose, talc, titanium dioxide. and other ingredients. The rapid-release pellets of diltiazem can be manu-

Fonmuln 2
Diltiazem HCI
Crodesta
56O OO o 5Q 5f) r o -'"" 7O Of'l u
I

fhctured by the following procedure: 2.00 kg of microgranules composed of sucrose and starch, with a particle size of 0.500-0.710 mm, are rotated in a trough with a stainless steel basket that is 450 mm in diameter. The rotating mass is sprayed, by means of a membrane-type proportioning pump, with 26 g of a 40o/o strength solution of shellac in ethanol and sprinkled with 80 g of diltiazem with a particle size of 40-80 Pm.

160

l(| | r Microcrystalline cellulose (Avicel nH 1.,.'-. Pcviclone K30

f')

5fi

MAN UFACTURING DIRECTIONS

Thc' sustained release pellets can be manufactured b1r fs1-

low'ing procedure: 2.00 kg of saccharose/st:u'ch pellet.s having a particle size between 0.500 and 0.710 mnl are pLrt in rotation in a suitable coating pan. The rotating tnass is sprayed with 27.2 g of an ethanolic solution coutaining 9.79 g of shellac and 1.09 -e of polyvinylpyrrcrlidone; and 80 g of diltiazem HCI are added. This operation is repeated 50 times. These pellets are then coated with the same amount of solution of ethylcellulose N100 and talc. respectivel)'. 80 g of 0.57o solution of ethylcellulose N100, and 5-1 g of talc. This operation is repeated 25 times. The proportion of soluble vs. insoluble coating materials can be altered to obtain the best release profile. All the formulations are tested for in vlrro dissolution, in the range of pH between 1 and 7.5, using the method described in the USP, paddle apparatus. Alternate methods of preparir-rg coated beads include first preparing beads and then coating them; the plain
beads are prepared by:

The ingredients are introduced in a planetary mixer ar-rd dry mixed for approximately 15 min. Thereafter, 100 ml purified water is added, and the mixing is pursued for 10 min nirre until a plastic mass is obtained. This rnass is tiren extruded through a Fuji Paudalo exiruder equi;ri-rcii with a 1-mm screen to obtain "spaghetti." A spheronrzel type caleva is used to transform the extruded product into beads. After drying for 12 h on trays in an oven at 60'C, the beads are sieved to eliminate the ones with a size l;rrger than i.4 mm and with a size srnaller than 0.7 mm. The amount of'beads obtained with sizes between 0.7 mm and 1.4 mm was 639.1 g (yield 91.3Vo). The beads prepared previously are then coated in a STREA- I (Aeromatic@) fluidized bed using the "top spral,ing" technique, and 440 g of coating suspension fron-t the following composition is applied on 500 -e of beads. Thereafter, the coated beads are dried at 50'C for l6 h.

ConrrNc SusprNsroru CoptposlrloN

\'lagnesiLrm stearate
12.50 g
-5.00 g

Titaniurn dioxide Povidone K30

Er"rdragit Nts30D

5.00 g 620.00 g
17.50 g

Talc
Water

338.00 g
I .{-X) g

Simethicone Tween 80

0.80 g

200,4 by CRC Press

LLC