Pharmaceutical Formulation and Development ( 2548)

Formulation of Conventional Tablets

...

3

1.
2.
3.
3
3 (controlled release dosage
form)



(active ingredient) (excipients)

(Preformulation Studies)

Pharmaceutical Formulation and Development

(physicochemical properties) UV spectroscopy

(absorbance) intrinsic solubility dissociation
constant (Ka) salt form

(solubility)

density, wettability, flow preperties compressibility
- Density

low potency
bulk density
segregration
- Wettability


contact angle
hydrophobic wettability

wettability hydrophilic excipient
surfactant
- Flow properties

(1) Compressibility (%)

Formulation of Conventional Tablets

Compressibility =

Tapped density Fluff density

100
Tapped density

3
3 Carrs index
Consolidation index (Carr)
5-15
12-16
18-21
23-35
33-38
> 40

Flow
Excellent
Good
Fair to passable
Poor
Very poor
Very very poor

compressibility consolidation
(compression)
(2) Hausner ratio
Hausner ratio = tapped density/fluff density Carrs index
1.25 ( 20% Carr) 1.5
( 33% Carr)
(3) Angle of Repose
4
4 Angle of repose Flowability
Angle of repose
< 25
25-30
30-40
> 40

Flow
Excellent
Good
Passable
Very poor

(4) flow rate

(orifice)
- Compression properties

Pharmaceutical Formulation and Development

pressure hardness profile

deformation characteristics elastic, plastic,

fragmentation Heckel plot

(punch 13 mm)

(kp)

(500 mg) + 1% magnesium stearate

A
B
C
5
5
30
1
1
1
30
2
2
24
24
24
A
B
C
Plastic
A<B
A>C
C<A<B

Fragmentation
A=B
A=C
A=B=C

plastic
(fracture) magnesium stearate

elasticity A, C cap laminate B

(elastic recovery)

dose

(Formulation of Conventional Tablets)

(Drug formulation)
(Peck et al., 1989)

Formulation of Conventional Tablets

1. (correct amount)


griseofulvin
(specific surface area)
2. (right form)
polymorph

3. (rate) (time)



4. (desired location)

1.

2.
3.

4.

5.

Pharmaceutical Formulation and Development

(
)

Chewable tablet

Sublingual tablet
nitroglycerin tablet
Buccal tablet sublingual tablet

methyltestosterone tablet
Effervescent tablet carbon dioxide

Vaginal tablet rectal tablet
oval pear bullet

Dispensing tablet

merculic chloride antiseptic solution cocaine

Multilayer tablet


Sugar coated tablet film-coated tablet

Compression coated tablet sugar coated tablet
film-coated tablet

4

1. (compressibility)
bonding

Formulation of Conventional Tablets

2. (flowability)

3. (wettability)

4. (lubricity)




(binder)

3

1. (dose)
paracetamol 500

Pharmaceutical Formulation and Development

steroid drug
binder solution
2.



3.

4. (bulk density)


5.

75
3

Formulation of Conventional Tablets

1.
2.
3.
4.
5.

(In-vitro test)

(In-vivo test)
USP USP
(in-vivo)

(validation)

10

Pharmaceutical Formulation and Development

(antiadherent)

2


(systemic
effect)

chlordiazepoxide



chlorpropamide
USP

Formulation of Conventional Tablets

11

starch

pregelatinized starch Starch-1500
polyvinylpyrolidone (PVP)
icing sugar
confectioners sugar


6

super disintegrant

starch
(elasticity)

12

Pharmaceutical Formulation and Development

Formulation of Conventional Tablets

13

6
Name

Strength

Comments

Water
Ethanol
a
Acacia mucilage
a
Tragacanth mucilage
Gelatin solutions

10-20
10-20
10-20

Starch mucilage
Glucose syrups
a
Sucrose syrups
b
PVP
a
Cellulose derivatives

5-10
25-50
65-85
3-15
5-10

Must be applied to easily hydratable material

Same as above
Hard, friable granules
Same as Acacia
Gels when cold; therefore use warm, strong adhesive
often use in lozenges; less attractive in warm moist
climate
One of best general binders, better use warm
Strongly adhesive, tablets may soften in high
Same as Glucose
Different MW grades give varying results
c
HPMC is most common

May also be added as dry powder to the formulation, giving a binding property when
moistened,
but this is less efficient than liquid preparation.
b
Polyvinyl
pyrrolidone
c
Hydroxypropylmethyl cellulose

magnesium stearate
plastic elastic Starch 1500, Elcema Avicel

14

Pharmaceutical Formulation and Development

Conners, K.A., Amidon G.I., Stella, V.J., 1986. Chemical stability of Pharmaceuticals, A
handbook for Pharmacists, 2nd Ed., John Wiley & Sons: Chichester.
Jaffe, H.H., Orchin M., Theory and Applications of UV Spectroscopy, John Wiley &
Sons: London.
Marshall, K., Rudnic, E.M., 1990. Tablet dosage forms. In: Modern Pharmaceutics,
Marcel Dekker: New York.
Peck,G.E., Baley, G.J., AcCurdy,V.E., Banker, G.S., 1990. Tablet Formulation and
Design. In Lieberman H.A., Lachmann, L., Scwartz.J.B. (Eds.) Pharmaceutical Dosage
Forms: Tablet, Vol. 1, Marcel Dekker: New York.
Racz, I. 1989. Drug Formulation, John Wiley & Sons: Chichester.
Swarbrick, J., 1970. Current concepts in the Pharmaceutical Sciences:
Biopharmaceutics, Lea & Febiger: Philadelphia.
Taylor, M.K., Ginsburg, J., Hickey, A., Gheyas, F., 2000. Composite method to quantify
powder flow as a screening method in early tablet or capsule formulation development.
AAPS PharmSciTech, 1(3), article 18.
Wade,A., Weller, P.J., 1994. Handbook of Pharmaceutical Excipients, Pharmaceutical
Press: London.
Wadke D.A., Serajuddin, A.T.M., Jacobson H., 1989. Preformulation Testing. In:
Lieberman H.A., Lachmann, L.,Scwartz. J.B. (Eds.) Pharmaceutical Dosage Forms:
Tablet, Vol. 1, Marcel Dekker: New York.
Wells, J.I., 1987. Pharmaceutical Preformulation: The Physicochemical Properties of
Drug Substances, Ellis Horwood: Chichester.
, 2543. .

, 2534.

. : . , . : .

 5
Diluents
Dextrose
Spray-dried lactose
Fast-flo lactose
Anhydrous lactose
Sucrose
Starch
Starch 1500
Dicalcium Phosphate
Emcompress
Avicel

Compactibility
3
3
4
2
4
2
3
3
3
5

Flowability
2
5
4
3
3
1
2
4
5
2

Solubility
4
4
4
4
5
0
2
1
0
0

Graded on a scale from 5 (good/high) down to 1 (poor/low); 0 means none.

Disintegration Hygroscopicity
2
1
3
1
4
1
4
5
4
4
4
3
4
3
2
1
3
1
2
2

Lubricity
2
2
2
2
1
3
2
2
1
4

Stability
3
4
4
4
4
3
4
5
5
5