Excipientes PARA Comprimidos

ClassicalExcipients
1. Fillers, Diluents / (Diluyentes) (their use is dependent on the drug dose)
Filler Functions:
Increase the bulk volume: final product has the proper volume for patient
handling
o drugs used at low doses: < 50 mg and diameter of tablet higher than 5
mm
o to minimize incompatibilities: the contact can be reduced by dilution
o Selection criteria: compressibility, compactibility, flow
Filler Requirements:
Inert, non-hygroscopic, soluble, cheap, compactable, tasteful
Lactosemonohydrate
o Natural disaccharide, obtained from milk: one glucose and one
galactose moiety
o Used as filler or filler-binder in the manufacture of pharmaceutical tablets
andcapsules Lactose may undergo a Maillard-type condensation
reaction with compounds containing a primary amine group to form
brownish colored products; this is accelerated in alkaline environments.
Lactose is listed as incompatible with amino acids, aminophylline
and amphetamines.
o Lactochemmilled
o Granulac 200, Granulac 230, Sorbolac 400, Granulac 140
o Prismalac 40, Capsulac 60, Sachelac 80, Spherolac 100

Powderedcellulose
o Derived from a natural polymer, hence it has a variable chain length and
variable molecular weight. It is slightly soluble in sodium hydroxide
solution. It is used as an adsorbent, glidant, suspending agent,
disintegrant and tablet/capsule diluent.
o Arbocel: Filler and binder for wet and dry granulation
o Emcocel 50M / Vivapur 101: aprox. 50 mm, Bulk density of 0.27 g/mL
o Granulation
Dibasiccalciumphosphate (CaHPO4)
o Anhydrous or contains two molecules water.
o Practically insoluble in water, insoluble in alcohol and soluble in 3 N HCl.
It should not be used to formulate tetracycline antibiotics and has
been reported to be incompatible with indomethacin, aspirin,
aspartame, ampicillin, cephalexin and erythromycin
o Good flow properties, but requires a lubricant when used for tableting.
o The surface of the particles is alkaline and should not be used with
drugs that are sensitive to alkaline pH.

 Starch (rice, wheat, corn, potato)

Natural starches contain 10-20% amylose and 80-90% amylopectin.
Starchesobtained from different sources may not have identical properties. As an
example, corn starch contains about 27% amylose, potato starch about 22% and
tapioca starch about 17%; these differences provide for different physical
properties. It is insoluble in cold water and in alcohol. Starch has no listed
incompatibilities

Sucrose / Saccharose
Sucrose may be contaminated with traces of heavy metals that can lead to an
incompatibility with active ingredients as ascorbic acid. It also may contain sulfite
from the refining process.
Others: mannitol, sorbitol, glucose, calcium carbonate
2. Binders / (Agregantes o aglutinantes) (2-10%)
Binder Functions:
-To ensure mechanical strength of tablets and granules
-To glue (promote adhesion) the particles together into granules helping to
hold the overall tablet together: Improves Compactibility
-To provide the cohesiveness to a formulation enhancing its compressibility
and flow properties (maintain the integrity of the tablet)
-to improve the mechanical strength of a tablet
-to improve the flowability of the powder or granules or both
Drawback: significant effect on bioavailability and therapeutic efficacy,
because it affects hardness and friability of tablet

Binders:
- Wet/Solution Binders: Gelatin, Cellulose derivatives, PVP, Starch, Sucrose,
PEG
- Dry Binders: Cellulose, Methyl cellulose, Polyvinylpyrrolidone, PEG
Hydrophillic cellulose derivatives
Hydroxypropylcellulose: Vivapharm: Low viscosity (1-4%, water, alcohol)
Carboxymethylcellulose (1-4%, water)

Ethylcellulose (0.5-2%, alcohol)

Methylcellulose (1-4%, water)

Starch (Starch 1500) (1-4%)

As a dry binder, it compresses well, predominately deforming plastically. It
can be used with other excipients, such as MCC, lactose, and dicalcium
phosphate, to produce tablets with excellent hardness and low friability at usual
compaction forces.
Slurry of Starch 1500 in cold water provides effective binding properties at
higher solids and lower viscosity than traditional starch pastes, which must be
heated and prepared at lower concentrations.

Polyvinylpyrrolidone(PVP): Plasdone (2-5%, alcohol, water)

Povidone is a high performance adhesive polymer primarily used as a versatile
wet granulation tablet binder. Ii is also used in the formulation of oral liquids and
suspensions, parenterals and topical products
Saccharose / Sucrose (2-20%, water) Microcristal 120
Gelatine (1-4%, water)
Acacia gum (2-5%, water, alcohol)
Tragacanth gum (1-3%, water)
PEG 4000 y 6000
Palmitate stearate glycerol / PEG
Others: glucose, sorbitol, excipients for direct compression (Elcema,
Avicel, Emcompress)

3. Disintegrants / disintegrating agents: 1 al 5%.

Disintegrant Functions: To ensure that when tablets are in contact with water,
they are rapidly breaking into smaller fragments, facilitating their dissolution.
They function primarily by drawing water into the tablet while simultaneously
swelling.
-Important for immediate release products where rapid release is required
-more effective if added 50% intragranularly, and 50% extra-granularly
(i.e., in the final dry mixture)
-Some tablet fillers (e.g., starch and MCC) aid in disintegration
-Selection criteria: Active / drug dissolution, bioavailability
Starch and starch derivatives (5-15%)
Starch 1500: 2-10% provides super disintegrant actions, reducing costs.
It has been shown to exhibit a lower propensity for moisture, thus
providingexcellent stabilization of moisture-sensitive active (eg, aspirin,
hydrochlorthiazide).
Cellulose derivatives
Avicel RC591: mixture of MCC and carboxymethycellulose sodium
Polysaccharides
Alginic acid, sodium alginate, tragacanth gum
Guar gum (Vidogum GH)
Methylated caseine: EsmaSpreng
Colloidalsilicondioxide: Aerosil, Cab-O-Sil
Magnesium Aluminum Silicate: Veegum F
Disintegrant Mechanisms
All are hygroscopic and draw liquid into the matrix ("liquid uptake" or "wicking action")

 As they sorb liquid, they may:

Swell extensively (Sodium Starch Glycolate)
Recover shape with little swelling (Crospovidone; Starch)
Swell radially and straighten out [fibrous material] (Croscarmellose)
Together, these phenomena create a disintegrating force within the matrix
Superdisintegrants (0.5-2.0%, Can be used up to 5.0%)
They draw large amounts of water while simultaneously swelling
For powder filled hard gelatin capsules, 4-8% is usually used.
Crospovidone and Starch are not recommended for capsules.
Sodium starch glycolate: Primojel , Explotab (1-6%)
High concentrations may cause gelling and loss of disintegration.
Croscarmellose sodium / carboxy methyl cellulose: VivaSol, Ac-Di-Sol
(0.5-5%)
High swelling capacity, effective at low concentrations
DC: 1-3%, wet granulation: 2-4%
Soy polysaccharides: Emcosoy - High-fiber, starch-free disintegrant.
Crospovidone / Cross-linked PVP: Polyplasdone XL (2-4%)
Insoluble in water but it disperses and swells in water
Greatest rate of swelling compared to other disintegrants.
L-HPC Low-substituted hydroxyl propyl cellulose (1-5%)
Insoluble in water. Rapidly swells in water.

4. Lubricants 0.5 a 2%.

To prevent the compacted powder from sticking to the equipment during the tabletting.
It aids ejection of the tablet from the dies, and may improve powder flow.
Lubricant Roles
True Lubricant Role: reducing friction between sliding surfaces, at the tabletdie wall interface during tablet formation and ejection. Also applies to capsule
plugs.
Anti adhesion Role: Preventing sticking to surfaces. To reduce adhesion
between the powder and the punch faces and thus prevent tablet sticking to the
punches.
Glidant Role / deslizante: Improving flow by modifying the interaction
between particles
Concept of a "Lubricant System"
Frequently two substances are used in a formulation to maximize
lubricant effect in all three areas: combining magnesium stearate with
colloidal silica
Lubricant Issues
o The most effective true lubricants are hydrophobic and if too much is
used, they can interfere with disintegration and dissolution
o Lubricant generally interfere with bonding and can soften tablets

o Alkaline metal stearates are incompatible with some drugs, e.g.

aspirin and AA
o Laminar lubricants (Mg stearate, Ca stearate) are "mixing sensitive
Under the rigors of mixing they delaminate: effect equivalent to adding
too much lubricant
o Lubricants are always added last after all other components have
been thoroughly mixed (mixing time of 2-5 min)
o Water soluble lubricants are not as effective: for water soluble tablets
Magnesium Stearate (< 1%)
Blending times should be limited. Over blending can cause compaction
problems.
Stearic Acid (1-5%)
Not as effective as magnesium stearate, but used in combination with Mg St, to get
a synergistic lubricant effect on punch faces and die walls.
Doesn't have the over blending problems seen with MgSt
Vegetable based Fatty Acids (90% palmitic/stearic acid) (3-5%)
Good tablet hardness, good for chewable tablets. Less sensitive to over
blending than metal stearates. Less reactive, can be used with acidic substances.
Sodium Benzoate, PEG 20.000, Levilita, glycine,sodium lauryl sulphate
PRUV (Sodium Stearyl Fumarate) - less reactive hydrophilic lubricant
Extremely effective lubricant at low concentrations. Expensive. Doesn't have the
over blending problems seen with MgSt.

Glidants (optimum of concentration of about 0.25-0.5%)

_Usually added to enhance the flowability of direct compression mixtures.
_Higher concentrations needed to correct serious adhesion (sticking) to punch
faces
Talc (1-5%)
Starch: Starch 1500 (5-10%)
Good strategy to lower the levels of traditional lubricants (Mg St)
Colloidal silicon dioxide: Aerosil / Aerosil200 VV or compacted CSD,
Labosil
Advantages Aerosil 200 VV over non-compacted colloidal silicon dioxide include
reduced dusting and better handling during weighing and dosing
- Powders/Granules: 0.2-1%. As anti-caking agent, adsorbent moisture 15-50%
- Tablets: glidant 0.2-1%, improves hardness and tablet disintegration

Lubricants (Magnesium Stearate)

Prevent the formulation and formed tablet from sticking to machinery
Blending times critical

Weaker tablet compacts

Slower drug dissolution

Glidants (Silica / Talc)

Improves flowability of powders/granulation
Allows formulation to flow easily through tableting machine
Flowability measured using angle of repose or Flowdex
5. Miscellaneous
Sorbent: limited fluid sorbing in dry state
Colors: Self apparent
Flavors and Sweeteners
Spray-dried and other flavors
Natural sweeteners
Artificial sweeteners
Mask bad taste of drugs/excipients
Mask bad odor
Protective Agents
Other
Direct compression excipients
Characteristics
- Generally, direct compression Filler-Binders are common fillers that have been
physically modified.
- Fillers possesses both diluent and binders properties; sometimes, also glidants
- In general, these excipients are used in a large amount (50-80%)
- Main aspect: Improving Flowability (add glidants)
Today, tableting equipment compressing 8,000 to 10,000 tablets per minute. It is
critical to have an excellent flowing granulation/powder blend. Many sugar-based
excipients, such as maltose, mannitol, and sorbitol are not compressible in their natural
state and need to be modified for use in direct compression table ting

Classification: 4 groups
- Cellulose derivatives
- Starch derivatives
- Sugars
- Mineral products

1. Cellulose and derivatives

a) Microcrystaline cellulose, MCC
Binder properties: tablet compactibility: low friability
Inherent lubricant properties: tablets self disintegrate and require little lubricant
Most compactible material available for pharmaceutical use
Avicel PH-101, PH-102, PH-103, PH-105, PH-112, PH-200
Emcocel: contains a little amount of calcium phosphate
ProSolv SMCC: combination of MCC and colloidal silicon dioxide. Permits
to reduce binder usage by more than half, cutting tablet size consequently.
Hence, itis ideally suited to high-dose or multiple actives direct-compression
formulations in which it has advantages in both flow and compactability over
conventional MCC.
Others: Vivacel, VivaPur
b) Powdered celluloses
Elcema: a-cellulose
Elcema P050: 1 - 50 mm; Elcema P100: 1 - 100 mm; Elcema F150: 1 - 150
mm;
Elcema G250 granulate: 90 - 250 mm; Elcema G400: 130 - 260 mm
Solka-Floc and JustFiber
Rapid disintegration
Reduce capping to improve the efficiency manufacturing process and uniformity
tablets
Ability to absorb moisture
2. Starch and starch derivatives
Starch is formed by amylose, glucose and amilopectine.
- Binder
- Self-lubricant: permits to reduce the amount of traditional lubricants
- Super disintegrant: 2-10% of Starch 1500 provides disintegrant action as effective as
super disintegrants, greatly reducing costs and improving stability and film coating
quality.
- Flow aid: excellent flow properties, demanded by today's high-speed tableting
equipment; ensuring that manufacturers can produce tablets with consistent uniform
weight and drug content. In formulations containing starch, it is necessary to
include excipients able to increase the compactability (the hardness of the
resulting tablet): 5-10% Silartex or Compressil (magnesium silicate)
Starch 1500
promotes formulation flexibility by complementing and enhancing the functionality of
other excipients.
Sta-Rx 1500
Paygel 90
3. Sugars
a). Lactose
Lactochem: a-monohydrate lactose. Available in sieved and milled forms (this
last one for wet granulation). Sieved Lactochem products have very good

flowability and can be used for filling of capsules and sachets, wet granulation
tabletting and diluents for direct compression
Lactopress: 2 different forms, good flowability and excellent compactability
Lactopress spray-dried: a-monohydrate lactose particles that are 'glued'
byamorphous lactose (up to 15%). Superior compactability with a spherical
shape (highflow). It permits to decrease the amount of lubricants required (0.2%
vs 0.5-1%).
Lactopress anhydrous characterized by superior dissolution and binding
properties. Adequate choice for moisture-sensitive actives or formulations for
DC.
Microcelac 100 is a spray-dried compound containing 75 % -lactose
monohydrate and 25 % MCC. Both filling properties of lactose and binding
capacity of MCC. Low cost. Angle of repose: 34
Ludipress: lactose (93.4%), Kollidon 30 (3.2% PVP, binder) and
Kollidon CL (3.4% cross-linked PVP, flow aid). It is also suitable as a filler
for hard capsules
Starlac: Lactose / Starch (85:15)
Others: Zeparox, DCL-30, Pharmatose,Tablettose, Lactose Fast
Flow, Flowlac 100,Cellactose 80

b) Compressible Sugar
Used in chewable tablets
Mini granulation of sugar crystals "glued" together with amorphous dextrins
Compressible Sugar (95-98% sucrose)
It may contain starch, maltodextrin or invert sugar and a suitable lubricant.
White, granular, free-flowing powder and sweet taste. Very soluble in water, non
hygroscopic, non-reactive with other tablet ingredients. Slightly soluble in
alcohol.
Di-Pac: excellent flowability, high compressibility, low hygroscopicity, sweet
and non-reactive. It contains 97% sucrose and 3% maltodextrines.
SugarTAB's excellent carrier for materials with compression problems
Compressuc: Saccharose + Maltodextrines
Others: NU-TAB 4001, Sucre CD1: Tabfine S100 I
c) Glucose / Dextrose
Emdex (Dextrates) - The first highly compatible soluble excipient. High
flowability and compressibility. Water solubility, sweet, rapid dissolution and
freshly sensations in mouth.
Glucose (90-92%), maltose (3-5%) and little amounts of polysaccharides.
Tabfine D97 HS: glucose (97%) and starch (3%) as binder.
d) Fructose / Levulose
Tabfine F94 M: fructose (96%) and maltose (4%).

e) Sorbitol
It is the most common bulking agent for sugar-free products. Its compressibility enables
the production of hard and smooth tablets by direct compression techniques.
Neosorb: for tablets produced either following wet granulation or by DC.
Neosorb60 (10%max>315 mm), Neosorb60W (105-420 mm)
Neosorb crystal 20/60 (0.2-1 mm)
f) Mannitol
Pearlitol: low hygroscopicity and excellent chemical stability. For different
processes: wet or dry granulation, direct compression. It allows sugar-free
formulations (including chewing gums), because it is the least soluble and
least hygroscopic crystalline polyol
g) Maltose
Advantose 100: disaccharide, with flow and tableting properties that are
greatly improved by the process of spray drying. Advantose particles are
spherical with good flow properties. When compared to MCC, it can tolerate
greater compression forces without capping upon ejection from the tableting
die. It also exhibits lower hygroscopicity and lower reactivity. It can be also used
as sugar substitute for great tasting sugar-free and low-calorie products.
h) Maltitol
Maltisorb is well suited to the formulation of powder forms (sachets, dry
syrups capsules) and tablet forms, whether chewable, suck able, coated or
effervescent.
4. Mineral products
a. Dibasic calcium phosphate dihydrate: CaHPO42H2O
Binder properties: tablet compactibility
Emcompress (Dibasic calcium phosphate dihydrate) - The first
directlycompressible excipient. Diluyent and binder properties. High density
Emcompressanhidrous: similar to Emcompress but especially designed for
drugs sensible to moisture
A-TAB (anhidrous), Calstar, Di-TAB
b. Tribasic calcium phosphate: Ca3(PO4)2; Ca5(OH)(PO4)3
Tri-CAL WG
Tri-TAB
c. Calcium Sulphate: Ca(SO4) ; CaSO42H2O
Compactrol: calcium sulfate with a particle size ideally suited for use in CD. It
is an efficient and relatively inexpensive tablet and capsule filler.
Non-hygroscopic: offers excellent long-term stability
High bulk density and free-flowing characteristics: adequate for high-speed
compaction and filling.
CAL-TAB
d. Hydrated magnesium silicate
They increase the compactability, the hardness of the resulting tablets
Silartex
Compressil

Bibliografa
1. Le Hir A. Farmacia galnica. Barcelona: Masson; 1995.
2. Vila Jato JL. Tecnologa farmacutica. Vol. I: Aspectos fundamentales de los
sistemas farmacuticos y operaciones bsicas. Madrid: Sntesis; 1997.
3. Vila Jato JL. Tecnologa farmacutica. Vol. II: Formas farmacuticas. Madrid:
Sntesis; 1997.
4. Faul i Trillo C. Tratado de farmacia galnica. Madrid: Luzn 5; 1993.
5. Gennaro AR. (Ed.) Remington: The Science and Practice of Pharmacy. 20. ed.
Easton: Mack Publishing Company; 2000.
6. Lieberman HA, Lachman, L. Pharmaceutical Dosage Forms: Tablets. Vol. 2. Nueva
York: Marcel Dekker; 1981.
7. Faul y Trillo, C. (1993). Tratado de Farmacia Galnica, Luzn 5, S.A. de Ediciones,
Madrid.
8. Aiache, J. M., Aiache, S. y Renoux, R. (1996). Introduccin al estudio del
medicamento, 2 ed., Ed. Masson, Barcelona.
9. Aulton, M.E. (1988). Pharmaceutics. The science of dosage form design. Churchill
Livingstone, New York.
10.
L.L. Augsburger, S. W. Hoag, Pharmaceutical Dosage Forms: Tablets. 3rd ed.
Informa Healthcare.New York. 2008