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Overview of pharmaceutical excipients used in tablets and capsules
The pharmaceutical industry is ever thirsty to satisfy patient’s therapeutical needs and apart from active ingredients, inactive excipients play a major role in formulation development. Pharmaceutical excipients are substances other than the pharmacologically active drug or prodrug which are included in the manufacturing process or are contained in a finished pharmaceutical product dosage form.
In addition to transporting the active drug to the site in the body where the drug is intended to exert its action, excipients play an important part in the manufacturing process. They may also be important for keeping the drug from being released too early in the assimilation process in places where it could damage tender tissue and create gastric irritation or stomach upset.
Others help the drug to disintegrate into particles small enough to reach the blood stream more quickly and still others protect the product's stability so it will be at maximum effectiveness at time of use. In addition, some excipients are used to aid the identification of a drug product.
Last, but not least, some excipients are used simply to make the product taste and look better. This improves patient compliance, especially in children. Although technically "inactive" from a therapeutic sense, pharmaceutical excipients are critical and essential components of a modern drug product. In many products, excipients make up the bulk of the total dosage form (1). Apart from the drug’s active ingredient, other essential components include diluents or fillers, binders, disintegrants, lubricants, coloring agents and preservatives (3). Diluents or fillers are inert ingredients that can significantly affect the chemical and physical properties of the final tablet thus affecting the biopharmaceutical profile.
One classic example of this are calcium salts, which can be utilized as fillers, which interfere with the absorption of tetracycline from the gastrointestinal tract. (4) This example emphasizes that excipients may not always be inert, as they may be perceived.
Usually tablets are designed so that the smallest tablet size which can be conveniently compressed is formed. Thus, if the dose is small more diluents are required and if the dose is high less diluents are required as not to increase the tablet size, which might make it difficult to swallow.
Diluents selection should be made carefully as physical-chemical changes might render the product unstable and might cause problems in manufacturing. Binders are added to tablet formulations to add cohesiveness to powders thereby providing the necessary bonding to form granules which under compaction form a compact mass as tablet. In other words, binders are essential to achieve the “hardness” of the tablet.
Binders are usually selected on basis of previous experience, particular product needs, literature or vendor data or the preference of individual scientists or manufacturing unit. The primary criterion when choosing a binder is its compatibility with other tablet components.
It must add sufficient cohesion to the powders to allow for normal processing yet allow the tablet to disintegrate and the drug to dissolve upon ingestion, releasing the active ingredients for absorption. Disintegrants facilitate the breakup of a tablet after oral administration.
They can be added prior to granulation or during the lubrication step prior to compression or at both processing steps. The effectiveness of many disintegrants is affected by their position within the tablet. Since disintegration is the opposite operation to granulation (agglomeration) and the subsequent formation of strong compacts, one must carefully weigh these two phenomena when designing a tablet. Lubricants prevent sticking of the tablets to the tablet punches during the compression phase of the tablet manufacturing process.
When lubricants are added to a powder mass, they form a coat around individual particles which remains more or less intact during compression. Lubricants are mostly hydrophobic. The presence of lubricant coating may cause an increase in the disintegration time and a decrease in drug dissolution rate. The choice of a lubricant may depend upon the type of tablet being manufactured, dissolution, flow characteristics and requirements of the formulation in terms of hardness, friability and compatibility. Glidants are the materials that have good flow properties and poor lubrication properties.
Glidants improve the flow of powder into the tableting machines for compaction. They act to minimize the tendency of a granulation to separate or segregate due to excessive vibration. High speed tablet machine require smooth even flow of material to die cavities (tablet mold). The uniformity of tablet weights directly depends on how uniformly the die cavity is filled. In general many materials commonly referred to as lubricants possess only a minimal lubricating activity and are better glidants or anti-adherents.
Thus a blend of two or more materials may be necessary to obtain these properties. Pharmacists should be familiar with the components of pharmaceuticals products, beyond their active ingredients. In order to educate pharmacists on excipients that are routinely used in the pharmaceutical industry, we decided to examine the top 200 prescription tablets and capsules products of 2003 (2) and find out how many or which excipients are used in each product.
The selection will cover both brand and generic drugs. Out of the 200 prescription drugs, the total numbers of inactive excipients used except for coating and coloring agents were ONLY 94! Although the list is composed on the top 200 drugs of 2003, very few blockbusters has been launched since then and still the excipients in all remains the same.
1
Acacia
Emulsifying agent; stabilizing agent; suspending agent; tablet binder; viscosity-increasing agent
2
Alginate
Binder
3
Alginic Acid
Stabilizing agent;
suspending agent;
tablet binder,
tablet disintegrant;
viscosity-increasing agent.
4
Aluminum Acetate
Antiseptic
5
Benzyl Alcohol
Antimicrobial preservative; disinfectant; solvent
6
Butyl Paraben
Antimicrobial preservative
7
Butylated Hydroxy Toluene
Antioxidant.
8
Citric acid
Disintegrant
9
Calcium carbonate
Tablet and capsule diluent; therapeutic agent
10
Candelilla wax
Binder
11
Croscarmellose sodium
Tablet and capsule disintegrant
12
Confectioner sugar
Sugar coating adjunct; sweetening agent; tablet and capsule diluents
13
Colloidal silicone dioxide
Adsorbent; anticaking agent; emulsion stabilizer; glidant;
suspending agent; tablet disintegrant; thermal stabilizer;
viscosity-increasing agent.
14
Cellulose
Adsorbent; suspending agent; tablet and capsule diluent;
tablet disintegrant.(cellulose microcrystaline) Adsorbent; glidant; suspending agent;
tablet and capsule diluent; tablet disintegrant (cellulose powdered) Tablet and capsule diluent.(cellulose Silicified)
15
Plain or anhydrous calcium phosphate
Diluent
16
Carnuba wax
Binder
17
Corn starch
Binder
18
Carboxymethylcellulose calcium
Stabilizing agent; suspending agent;
tablet and capsule disintegrant;
viscosity-increasing agent; water-absorbing agent
19
Calcium stearate
Tablet and capsule lubricant
20
Calcium disodium EDTA
Chelation
21
Copolyvidone
Film-former; granulating agent; tablet binder
22
Castor oil hydrogenated
Extended release agent; stiffening agent; tablet and
capsule lubricant
23
Calcium hydrogen phosphate dihydrate
Diluent
24
Cetylpyridine chloride
Antimicrobial preservative; antiseptic;
cationic surfactant; disinfectant;
solubilizing agent; wetting agent
25
Cysteine HCL
Reducing Agent
26
Crosspovidone
Tablet disintegrant.
27
calcium phosphate di or tri basic
Tablet and capsule diluent Anticaking agent; buffer, nutrient; dietary supplement;
glidant; tablet
and capsule diluent and
clouding agent( for calium phosphage tribasic)
28
Dibasic Calcium Phosphate
Diluent
29
Disodium hydrogen phosphate
Buffering agent
30
Dimethicone
Antifoaming agent;
emollient
31
Erythrosine Sodium
Color
32
Ethyl Cellulose
Coating agent;
flavoring fixative;
tablet binder;
tablet filler;
viscosity-increasing agent.
33
Gelatin
Coating agent;
film-former;
gelling agent;
suspending agent;
tablet binder;
viscosity-increasing agent
34
Glyceryl monooleate
Nonionic surfactant
35
Glycerin
Antimicrobial preservative;
emollient;
humectant;
plasticizer;
solvent;
sweetening agent;
tonicity agent
36
Glycine
Tonicity
37
Glyceryl monostearate
Emollient; emulsifying agent;
solubilizing agent;
stabilizing agent;
sustained-release ingredient;
tablet and capsule lubricant
38
Glyceryl behenate
Coating agent; tablet binder; tablet and capsule lubricant
39
Hydroxy propyl cellulose
Coating agent; emulsifying agent;
stabilizing agent; suspending agent;
tablet binder; thickening agent;
viscosity-increasing agent.
40
Hydroxyl propyl methyl cellulose
Coating agent; film-former;
rate-controlling polymer for sustained release;
stabilizing agent; suspending agent; tablet binder; viscosity-increasing agent.
41
Hypromellose
Coating agent; film-former;
rate-controlling polymer for sustained release; stabilizing agent;
suspending agent; tablet binder; viscosity-increasing agent.
42
HPMC Pthalate
Coating agent.
43
Iron oxides or ferric oxide
Color
44
Iron oxide yellow
Color
45
Iron oxide red or ferric oxide
Color
46
Lactose hydrous or anhydrous or monohydrate or spray dried
Binding agent; diluent for dry-powder inhalers; lyophilization aid;
tablet binder; tablet and capsule diluent.( lactose anhydrous) Binding agent; diluent for dry-powder inhalers; tablet binder;
tablet and capsule diluent(lactose monhydrate) Binding agent; diluent for dry-powder inhalations; tablet and capsule diluent;
tablet and capsule filler.(lactose spray dried)
47
Magnesium stearate
Tablet and capsule lubricant
48
Microcrystalline cellulose
Adsorbent; suspending agent; tablet and capsule diluent; tablet disintegrant same as cellulose see above it is just that mcc is usp
49
Mannitol
Sweetening agent; tablet and capsule diluent; tonicity agent;
vehicle (bulking agent) for lyophilized preparations
50
Methyl cellulose
Coating agent; emulsifying agent; suspending agent;
tablet and capsule disintegrant; tablet binder; viscosity-increasing agent
51
Magnesium carbonate
Tablet and capsule diluent
52
Mineral oil
Emollient; lubricant; oleaginous vehicle; solvent
53
Methacrylic acid copolymer
Coating
54
Magnesium oxide
Tablet and capsule diluent
55
Methyl paraben
Antimicrobial preservative
56
Povidone or PVP
Disintegrant; dissolution aid; suspending agent; tablet binder.
57
PEG
Ointment base; plasticizer; solvent; suppository base;
tablet and capsule lubricant
58
Polysorbate 80
solubilizer
59
Propylene glycol
Antimicrobial preservative; disinfectant; humectant; plasticizer;
solvent; stabilizer for vitamins; water-miscible cosolvent.
60
Polyethylene oxide
Mucoadhesive; tablet binder; thickening agent.
61
Propylene paraben
Antimicrobial preservative
62
Polaxamer 407 or 188 or plain
Dispersing agent; emulsifying and coemulsifying agent;
solubilizing agent; tablet lubricant; wetting agent.
63
Potassium bicarbonate
Alkalizing agent; therapeutic agent
64
Potassium sorbate
Antimicrobial preservative
65
Potato starch
Binder
66
Phosphoric acid
Acidifying agent
67
Polyoxy140 stearate
Emulsifying agent; solubilizing agent; wetting agent
68
Sodium starch glycolate
Tablet and capsule disintegrant
69
Starch pregelatinized
Tablet and capsule diluent; tablet and capsule disintegrant;
tablet binder (starch pregelatinized Glidant; tablet and capsule diluent; tablet and capsule disintegrant;
tablet binder.( starch , potato, corn , wheat, rice) so check the above and make the changes
70
Sodium crossmellose
Disintegrant
71
Sodium lauryl sulfate
Anionic surfactant; detergent; emulsifying agent;
skin penetrant; tablet and capsule lubricant; wetting agent
72
Starch
Glidant; tablet and capsule diluent; tablet and capsule disintegrant;
tablet binder.( starch , potato, corn , wheat, rice) combine all the starches
73
Silicon dioxide
Same as colloidal silicon dioxide
74
Sodium benzoate
Antimicrobial preservative; tablet and capsule lubricant
75
Stearic acid
Emulsifying agent; solubilizing agent; tablet and capsule lubricant.
76
Sucrose
Base for medicated confectionery; granulating agent;
sugar coating adjunct; suspending agent; sweetening agent;
tablet and capsule diluent; viscosity-increasing agent.
77
Sorbic acid
Antimicrobial preservative
78
Sodium carbonate
Carbonating agent
79
Saccharin sodium
Sweetening agent
80
Sodium alginate
Stabilizing agent; suspending agent; tablet and capsule disintegrant;
tablet binder; viscosity-increasing agent.
81
Silica gel
Adsorbant
82
Sorbiton monooleate
Solubilizer
83
Sodium stearyl fumarate
Tablet and capsule lubricant.
84
Sodium chloride
Tablet and capsule diluent; tonicity agent
85
Sodium metabisulfite
Antioxidant.
86
Sodium citrate dihydrate
Alkalizing agent; buffering agent; emulsifier; sequestering agent.
87
Sodium starch
Binder
88
Sodium carboxy methyl cellulose
Coating agent; tablet and capsule disintegrant;
tablet binder; stabilizing agent; suspending agent;
viscosity-increasing agent; water-absorbing agent.
89
Succinic acid
Acidity
90
Sodium propionate
Antimicrobial preservative
91
Titanium dioxide
Coating agent; opacifier; pigment
92
Talc
Anticaking agent; glidant; tablet and capsule diluent; tablet and capsule lubricant.
93
Triacetin
Humectant; plasticizer; solvent
94
Triethyl citrate
Plasticizer
From the table above we see that most of the commonly used ingredients have not been changed in making a tablet from generations and might follow the same trends for many generations to come.
CONCLUSION: Lot of time and effort are still needed in field of excipients. However till then a formulation scientist is entrusted with the limited amount of excipients and will have to deal with 94 excipients or now maybe 104.
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