Dear pharma friends,
This is in continuation of my earlier article about tablet making technology today we shall see about excipients
Let us get to know about some excipients their categories, properties and their role in tablet making
I hope these are some basic terminologies that every shop floor pharmacist should basically aware of.
Apart from being a filler to match tablet weight to their tooling size,
The excipients under various categories mentioned here under have some vital and specific role in easing the tablet formation in the machine, as binder, lubricant and glidant.
a.protecting tablets during their shelf life,
As coating colour
B.Enable the release of drug from tablet disintegrate in water to release the drug (disintegrate) etc
Let us see all these categories in brief.
Excipients
Anti adherentsl
Anti adherents reduce the adhesion between the powder (granules) and the punch faces and thus prevent sticking to tablet punches by offering a non-stick surface. They are also used to help protect tablets from sticking. The most commonly used is magnesium stearate.
Binders
Binders hold the ingredients in a tablet together. Binders ensure that tablets and granules can be formed with required mechanical strength, and give volume to low active dose tablets. Binders are usually:
Saccharides and their derivatives:
Disaccharides: sucrose, lactose;
Polysaccharides and their derivatives: starches, cellulose or modified cellulose such as microcrystalline cellulose and cellulose ethers such as hydroxypropyl cellulose (HPC);
Sugar alcohols such as xylitol, sorbitol or mannitol;
Protein: gelatin;
Synthetic polymers: polyvinylpyrrolidone (PVP), polyethylene glycol (PEG)...
Binders are classified according to their application:
Solution binders are dissolved in a solvent
(for example water or alcohol can be used in wet granulation processes).
Examples include gelatin, cellulose, cellulose derivatives, polyvinylpyrrolidone, starch, sucrose and polyethylene glycol.
Dry binders are added to the powder blend, either after a wet granulation step, or as part of a direct powder compression (DC) formula. Examples include cellulose, methyl cellulose, polyvinylpyrrolidone and polyethylene glycol.
Coatings
Tablet coatings protect tablet ingredients from deterioration by moisture in the air and make large or unpleasant-tasting tablets easier to swallow. For most coated tablets, a cellulose ether hydroxypropyl methyl cellulose (HPMC) film coating is used which is free of sugar and potential allergens. Occasionally, other coating materials are used, for example synthetic polymers, shellac, corn protein zein or other polysaccharides. Capsules are coated with gelatin.
Enterics control the rate of drug release and determine where the drug will be released in the digestive tract. Materials used for enteric coatings include fatty acids, waxes, shellac, plastics, and plant fibers.
Colors
Colors are added to improve the appearance of a formulation. Color consistency is important as it allows easy identification of a medication. Furthermore, colors often improve the aesthetic look and feel of medications. Small amounts of coloring agents are easily processed by the body, although rare reactions are known, notably to tartrazine.[7] Commonly, titanium oxide is used as a coloring agent to produce the popular opaque colors along with azo dyes for other colors. By increasing these organoleptic properties a patient is more likely to adhere to their schedule and therapeutic objectives will also have a better outcome for the patient especially children.
Disintegrants
Disintegrants expand and dissolve when wet causing the tablet to break apart in the digestive tract, or in specific segments of the digestion process, releasing the active ingredients for absorption. They ensure that when the tablet is in contact with water, it rapidly breaks down into smaller fragments, facilitating dissolution.
Examples of disintegrants include:
Crosslinked polymers: crosslinked polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethyl cellulose(croscarmellose sodium).
The modified starch sodium starch glycolate.
Flavors
Flavors can be used to mask unpleasant tasting active ingredients and improve the acceptance that the patient will complete a course of medication. Flavorings may be natural (e.g. fruit extract) or artificial.[11][7]
For example, to improve:
a bitter product - mint, cherry or anise may be used
a salty product - peach, apricot or liquorice may be used
a sour product - raspberry or liquorice may be used
an excessively sweet product - vanilla may be used
Glidants
Glidants are used to promote powder flow by reducing interparticle friction and cohesion. These are used in combination with lubricants as they have no ability to reduce wall friction. Examples include silica gel, fumed silica, talc, and magnesium carbonate. However, some silica gel Glidants such as Syloid(R) 244 FP and Syloid(R) XDP are multi-functional and offer several other performance benefits in addition to reducing interparticle friction including moisture resistance, taste marketing etc.
Lubricants
Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low friction between the solid and die wall.[
Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid are the most frequently used lubricants in tablets or hard gelatin capsules. Lubricants are agents added in small quantities to tablet and capsule formulations to improve certain processing characteristics. While lubricants are often added to improve manufacturability of the drug products, it may also negatively impact the product quality. For example, extended mixing of lubricants during blending may results in delayed dissolution and softer tablets, which is often referred to as "over-lubrication". Therefore, optimizing lubrication time is critical during pharmaceutical development.
There are three roles identified with lubricants as follows:
True lubricant role:
To decrease friction at the interface between a tablet’s surface and the die wall during ejection and reduce wear on punches & dies.
Anti-adherent role:
Prevent sticking to punch faces or in the case of encapsulation, Lubricants Prevent sticking to machine dosators, tamping pins, etc.
Glidant role:
Enhance product flow by reducing interparticulate friction.
There are two major types of lubricants:
Hydrophilic
Generally poor lubricants, no glidant or anti-adherent properties.
Hydrophobic
Most widely used lubricants in use today are of the hydrophobic category. Hydrophobic lubricants are generally good lubricants and are usually effective at relatively low concentrations. Many also have both anti-adherent and glidant properties. For these reasons, hydrophobic lubricants are used much more frequently than hydrophilic compounds. Examples include magnesium stearate.
Preservatives
Some typical preservatives used in pharmaceutical formulations are
Antioxidants like vitamin A, vitamin E, vitamin C, retinyl palmitate, and selenium
The amino acids cysteine and methionine
Citric acid and sodium citrate
Synthetic preservatives like the parabens: methyl paraben and propyl paraben.
Sorbents
Sorbents are used for tablet/capsule moisture-proofing by limited fluid sorbing (taking up of a liquid or a gas either by adsorption or by absorption) in a dry state. For example, desiccants absorb water, drying out (desiccating) the surrounding materials.
Sweeteners
Sweeteners are added to make the ingredients more palatable, especially in chewable tablets such as antacid or liquids like cough syrup. Sugarcane be used to mask unpleasant tastes or smells, but articificial sweeteners tend to be preferred, as natural ones tend to cause tooth decay.
Vehicles
In liquid and gel formulations, the bulk excipient that serves as a medium for conveying the active ingredient is usually called the vehicle. Petrolatum, dimethyl sulfoxide and mineral oil are common vehicles.
In general following steps to be followed to get better results or expected results in tablet making.
1. Binders percentage should be sufficient enough to get tablets of requisite hardness without giving much pressure to the tabletting machine this would increase the longevity of punch es and does and prevent punch tip breakage.
It is most important to ensure that binders are completely dissolved and get into solution to get sufficient granules strength.
2. Disintegrants can be added as internal
During wet mixing and external during blending
3 Lubricants percentage of addition to any product would be normally very low
And their mixing time should be less in the order of 3 to 5 min In such cases it is more important to ensure that such a small quantities
get distributed to the entire bulk material during blending uniformly that too at short mixing time to give consistent test results during entire batch running time
So, to ensure this generally materials like stearate are sieved through fine mesh in the order 60#or80# there by
increasing the surface area of the material so that they blend to the large volume of the bulk uniformly and serves it's purpose of free ejection of the tablets without die wall friction, sticking etc.,
These are very basic steps to be followed during granulation process but normally overlooked to due to lack of knowledge about the basics of formulation technology and to end up in quarrel with product formulation during compression.
I hope this article would be helpful to freshers in shop floor who actually handle the processes so as to become conversant about materials their properties their action and ensure producing consistent quality products.
See you all in my next article about tablet compression.
Till then,
Cheers,
Srikanth santhanaraman.
P.S. please go through my earlier articles under the same heading to gain a better knowledge.
0 Comments