Tablets Dosage form is one of a most prefered dosage form all over the world

Almost all drug molecules can be formulated in a tablet and process of manufactiring of tablets too is very simple , and is very flexible.

One can administere 0.01 mg of a drug dose to 1 gm of a drug dose by oral route of administration , by formulating as a tablet.

We have decided to write about tablets manufacturing , formulations.

You will find our articles very intresting as , we are writng out of our experience of actual manufacturing of about 1000 different formulations and drugs , and not merily with therotical experience.

We will provide here on this blog case studies of tablets formulations , trouble shooting , development , tablets machineries tools and many intresting things about tablets formulations and tablets coating , our blog will guide for developing a cost effective and cheaper tablet coating materials .

Saturday, September 19, 2009

Tablet Dosage Form: Tablets dosage form advantages and disadvantages

Tablet Dosage form
A tablet is usually a compressed preparation that contains:
5-10% of the drug (active substance);
80% of fillers, disintegrants, lubricants, glidants, and binders; and
10% of compounds which ensure easy disintegration, disaggregation, and dissolution of the tablet in the stomach or the intestine.Pharmaceutical process validation


The disintegration time can be modified for a rapid effect or for sustained release.

Special coatings can make the tablet resistant to the stomach acids such that it only disintegrates in the duodenum as a result of enzyme action or alkaline pH.
Pharma Process Validation
Pills can be coated with sugar, varnish, or wax to diguise the taste.

Some tablets are designed with an osmotically active core, surrounded by an impermeable membrane with a pore in it. This allows the drug to percolate out from the tablet at a constant rate as the tablet moves through the digestive tract. here are  Pharmaceutical Validation  and

Tablet presses:tablets dosage form advantages and disadvantages

Tablet presses, also called tableting machines, range from small, inexpensive bench-top models that make one tablet at a time (single-station presses), no more than a few thousand an hour, and with only around a half-ton pressure, to large, computerized, industrial models (multi-station rotary or eccentric presses) that can make hundreds of thousands to millions of tablets an hour with much greater pressure. Some tablet presses can make extremely large tablets, such as some of the toilet cleaning and deodorizing products or dishwasher soap. Others can make smaller tablets, from regular aspirin to some the size of a bb gun pellet. Tablet presses may also be used to form tablets out of a wide variety of materials, from powdered metals to cookie crumbs. The tablet press is an essential piece of machinery for any pharmaceutical and nutraceutical manufacturer.
Pharmaceutical Validation
Pill-splitters
It is sometimes necessary to split tablets into halves or quarters. Tablets are easier to break accurately if scored, but there are devices called pill-splitters which cut unscored and scored tablets. Tablets with special coatings .Pharma .blogspot.com
(for example enteric coatings or controlled-release coatings) should not be broken before use, as this will expose the tablet core to the digestive juices, short-circuiting the intended delayed-release effect.this website http://www.tabletsdosageform.blogspot.com/ is dedicated for educting pharmaceuticle students
tablets dosage form advantages and disadvantages

Pharmaceutical process validation


Tablet coating: tablets dosage form advantages and disadvantages

Many tablets today are coated after being pressed. Although sugar-coating was popular in the past, the process has many drawbacks. Modern tablet coatings are polymer and polysaccharide based, with plasticizers and pigments included. Tablet coatings must be stable and strong enough to survive the handling of the tablet, must not make tablets stick together during the coating process, and must follow the fine contours of embossed characters or logos on tablets. Coatings can also facilitate printing on tablets, if required. Coatings are necessary for tablets that have an unpleasant taste, and a smoother finish makes large tablets easier to swallow. Tablet coatings are also useful to extend the shelf-life of components that are sensitive to moisture or oxidation. Opaque materials like titanium dioxide can protect light-sensitive actives from photodegradation. Special coatings (for example with pearlescent effects) can enhance brand recognition.
If the active ingredient of a tablet is sensitive to acid, or is irritant to the stomach lining, an enteric coating can be used, which is resistant to stomach acid and dissolves in the high pH of the intestines. Enteric coatings are also used for medicines that can be negatively affected by taking a long time to reach the small intestine where they are absorbed. Coatings are often chosen to control the rate of dissolution of the drug in the gastro-intestinal tract. Some drugs will be absorbed better at different points in the digestive system. If the highest percentage of absorption of a drug takes place in the stomach, a coating that dissolves quickly and easily in acid will be selected. If the rate of absorption is best in the large intestine or colon, then a coating that is acid resistant and dissolves slowly would be used to ensure it reached that point before dispersing. The area of the gastro-intestinal tract with the best absorption for any particular drug is usually determined by clinical trials.

This is the last stage in tablet formulation and it is done to protect the tablet from temperature and humidity constraints. It is also done to mask the taste, give it special characteristics, distinction to the product, and prevent inadvertent contact with the drug substance. The most common forms of tablet coating are sugar coating and film coating.
Pharmaceutical Process validation
Coating is also performed for the following reasons:

Controlling site of drug release
Providing controlled, continuous release or reduce the frequency of drug dosing
Maintaining physical or chemical drug integrity
Enhancing product acceptance and appearance
Sugar coating is done by rolling the tablets in heavy syrup, in a similar process to candy making. It is done to give tablets an attractive appearance and to make pill-taking less unpleasant. However the process is tedious and time-consuming and it requires the expertise of highly skilled technician. It also adds a substantial amount of weight to the tablet which can create some problems in packaging and distribution.
Pharmaceutical Validation
In comparison to sugar coating, film coating is more durable, less bulky, and less time consuming. But it creates more difficulty in hiding tablet appearance. The purpose of this coating is to prevent dissolution of the tablet in the stomach, where the stomach acid may degrade the active ingredient, or where the time of passage may compromise its effectiveness, in favor of dissolution in the small intestine, where the active principle is better absorbed.this website http://www.tabletsdosageform.blogspot.com/ is dedicated for educting pharmaceuticle students
tablets dosage form advantages and disadvantages

----Ad--pharmaguideline

Manufacturing Tabltes:tablets dosage form advantages and disadvantages

In the tablet-pressing process, it is important that all ingredients be dry, powdered, and of uniform grain size as much as possible. The main guideline in manufacture is to ensure that the appropriate amount of active ingredient is equal in each tablet so ingredients should be well-mixed. Compressed tablets are exerted to great pressure in order to compact the material. If a sufficiently homogenous mix of the components cannot be obtained with simple mixing, the ingredients must be granulated prior to compression to assure an even distribution of the active compound in the final tablet. Two basic techniques are used to prepare powders for granulation into a tablet: wet granulation and dry granulation.

Powders that can be mixed well do not require granulation and can be compressed into tablets through Direct Compression

Direct Compression
This method is used when a group of ingredients can be blended and placed in a tablet press to make a tablet without any of the ingredients having to be changed. This is not very common because many tablets have active pharamaceutical ingredients which will not allow for direct compression due to their concentration or the excipients used in formulation are not conducive to direct compression.

Granulation is the process of collecting particles together by creating bonds between them. There are several different methods of granulation. The most popular, which is used by over 70% of formulation in tablet manufacture is wet granulation. Dry granulation is another method used to form granules.

Wet granulation for tablets
Wet granulation is a process of using a liquid binder or adhesive to the power mixture. The amount of liquid can be properly managed, and overwetting will cause the granules to be too hard and underwetting will cause the granules to be too soft and friable. Aqueous solutions have the advantage of being safer to deal with than solvents.

Procedure of Wet Granulation for tablets
Step 1: Weighing and Blending - the active ingredient, filler, disintegration agents, are weighed and mixed.
Step 2: The wet granulate is prepared by adding the liquid binder/adhesive. Examples of binders/adhesives include aqueous preparations of cornstarch, natural gums such as acacia, cellulose derivatives such as methyl cellulose, CMC, gelatins, and povidone. Ingredients are placed within a granulator which helps ensure correct density of the composition.
Step 3: Screening the damp mass into pellets or granules
Step 4: Drying the granulation
Step 5: Dry screening: After the granules are dried, pass through a screen of smaller size than the one used for the wet mass to select granules of uniform size to allow even fill in the die cavity
Step 6: Lubrication- A dry lubricant, antiadherent and glidant are added to the granules either by dusting over the spread-out granules or by blending with the granules. Its reduces friction between the tablet and the walls of the die cavity. Antiadherent reduces sticking of the tablet to the die and punch.
Step 7: Tableting: Last step in which the tablet is fed into the die cavity and then compressed between a lower and an upper punch.
Water may be used as the liquid binder, but sometimes many actives are not compatible with water. Water mixed into the powder can form bonds between powder particles that are strong enough to lock them in together. However, once the water dries, the powders may fall apart and therefore might not be strong enough to create and hold a bond. Povidone also known as polyvinyl pyrrolidone (PVP) is one of the most commonly used pharmaceutical binders. PVP and a solvent are mixed with the powders to form a bond during the process, and the solvent evaporates. Once the solvent evaporates and powders have formed a densely held mass, then the granulation is milled which results in formation of granules

Dry granulation for tablets
Wet granulation is a process of using a liquid binder or adhesive to the power mixture. The amount of liquid can be properly managed, and overwetting will cause the granules to be too hard and underwetting will cause the granules to be too soft and friable. Aqueous solutions have the advantage of being safer to deal with than solvents. pharmaceutical validation

Procedure of Wet Granulation for tablets
Step 1: Weighing and Blending - the active ingredient, filler, disintegration agents, are weighed and mixed.
Step 2: The wet granulate is prepared by adding the liquid binder/adhesive. Examples of binders/adhesives include aqueous preparations of cornstarch, natural gums such as acacia, cellulose derivatives such as methyl cellulose, CMC, gelatins, and povidone. Ingredients are placed within a granulator which helps ensure correct density of the composition.
Step 3: Screening the damp mass into pellets or granules
Step 4: Drying the granulation
Step 5: Dry screening: After the granules are dried, pass through a screen of smaller size than the one used for the wet mass to select granules of uniform size to allow even fill in the die cavity
Step 6: Lubrication- A dry lubricant, antiadherent and glidant are added to the granules either by dusting over the spread-out granules or by blending with the granules. Its reduces friction between the tablet and the walls of the die cavity. Antiadherent reduces sticking of the tablet to the die and punch.
Step 7: Tableting: Last step in which the tablet is fed into the die cavity and then compressed between a lower and an upper punch.
Water may be used as the liquid binder, but sometimes many actives are not compatible with water. Water mixed into the powder can form bonds between powder particles that are strong enough to lock them in together. However, once the water dries, the powders may fall apart and therefore might not be strong enough to create and hold a bond. Povidone also known as polyvinyl pyrrolidone (PVP) is one of the most commonly used pharmaceutical binders. PVP and a solvent are mixed with the powders to form a bond during the process, and the solvent evaporates. Once the solvent evaporates and powders have formed a densely held mass, then the granulation is milled which results in formation of granules


Dry granulation for tablets
This process is used when the product needed to be granulated may be sensitive to moisture and heat. Dry granulation can be conducted on a press using slugging tooling or on a roller compactor commonly referred to as a chilsonator. Dry granulation equipment offers a wide range of pressure and roll types to attain proper densification. However the process may require repeated compaction steps to attain the proper granule end point.

Process times are often reduced and equipment requirements are streamlined; therefore the cost is reduced. However, dry granulation often produces a higher percentage of fines or noncompacted products, which could compromise the quality or create yield problems for the tablet. It requires drugs or excipients with cohesive properties.


Some granular chemicals are suitable for direct compression (free flowing) e.g. potassium chloride.
Tableting excipients with good flow characteristics and compressibility allow for direct compression of a variety of drugs.

Fluidized bed granulation
It is a multiple step process performed in the same vessel to pre-heat, granulate and dry the powders. It is today a commonly used method in pharmaceuticals because it allows the individual company to more fully control the powder preparation process. It requires only one piece of machinery that mixes all the powders and granules on a bed of air.


Tablet Compaction SimulatorTablet formulations are designed and tested using a laboratory machine called a Tablet Compaction Simulator or Powder Compaction Simulator. This is a computer controlled device that can measure the punch positions, punch pressures, friction forces, die wall pressures, and sometimes the tablet internal temperature during the compaction event. Numerous experiments with small quantities of different mixtures can be performed to optimise a formulation. Mathematically corrected punch motions can be programmed to simulate any type and model of production tablet press. Small differences in production machine stiffness can change the strain rate during compaction by large amounts, affecting temperature and compaction behaviour. To simulate true production conditions in today's high speed tablet presses, modern Compaction Simulators are very powerful and strong.

Initial quantities of active pharmaceutical ingredients are very expensive to produce, and using a Compaction Simulator reduces the amount of powder required for development.

Load controlled tests are particularly useful for designing multi-layer tablets where layer interface conditions must be studied. Pharmaceutical Process Validation

Test data recorded by the Simulators must meet the regulations for security, completeness and quality to support new or modified drug filings, and show that the designed manufacturing process is robust and reliable.this website http://www.tabletsdosageform.blogspot,com/ is dedicated for educting pharmaceuticle students
tablets dosage form advantages and disadvantages

Advantages and disadvantages of Tablet Dosage form

Tablets are easy and convenient to use. They provide an accurately measured dosage in a convenient portable package; and can be designed to protect unstable medications or disguise unpalatable ingredients. Coatings can be coloured or stamped to aid tablet recognition. Manufacturing processes and techniques can provide tablets special properties; for example enteric coatings or sustained release formulations. Pharmaceutical Validation

Some drugs may be unsuitable for administration by the oral route. For example protein drugs such as insulin may be denatured by stomach acids; such drugs cannot be made into tablets. Some may be deactivated by the liver (the "first pass effect") making them unsuitable for oral use. However, drugs which can be taken sublingually bypass the liver and are less susceptible to the first pass effect. Bioavailability of some drugs may be low due to poor absorption from the gastric tract; such drugs may need to be given in very high doses or by injection. For drugs that need to have rapid onset, or have severe side effects the oral route may not be suitable. For example Salbutamol can have effects on the heart and circulation if taken orally; these effects are greatly reduced by inhaling smaller doses direct to the required site of action.

.Pharma .blogspot.com
 Tablet properties
Tablets can be made in virtually any shape, although requirements of patients and tabletting machines mean that most are round, oval or capsule shaped. More unsusual shapes have been manufactured but patients find these harder to swallow, and they are more vulnerable to chipping or manufacturing problems.

Tablet diameter and shape are determined a combination of a a set of punches and a die. This is called a station of tooling. The thickness is determined by the amount of tablet material and the position of the punches in relation to each other during compression. Once this is done, we can measure the corresponding pressure applied during compression. The shorter the distance between the punches, thickness, the greater the pressure applied during compression, and sometimes the harder the tablet. Tablets need to be hard enough that they don't break up in the bottle, yet friable enough that they disintegrate in the gastric tract.
Pharmaceutical Process Validation
The tablet is composed of the Active Pharmaceutical Ingredient (that is the active drug) together with various excipients. These are biologically inert ingredients which either enhance the therapeutic effect or are necessary to construct the tablet. The filler or diluent (eg lactose or sorbitol)is a bulking agent, providing a quantity of material which can accurately be formed into a tablet. Binders eg methyl cellulose or gelatin) hold the ingredients together so that they can form a tablet. Lubricants (eg magnesium stearate or polyethylene glycol) are added to reduce the friction between the tablet and the punches and dies so that the tablet compression and ejection processes are smooth.
Disintegrants (eg starch or cellulose) are used to promote wetting and swelling of the tablet so that it breaks up in the gastro intestinal tract; this is necessary to ensure dissolution of the API. Superdisintegrants are sometimes used to greatly speed up the disintegration of the tablet. Additional ingredients may also be added such as coloring agents, flavoring agents, and coating agents. Formulations are designed using small quantities in a laboratory machine called a Powder Compaction Simulator. This can prove the manufacturing process and provide information for the regulatory authorities.
Pharma process validation

Advantages and disadvantages of Tablet Dosage form

Tablets are easy and convenient to use. They provide an accurately measured dosage in a convenient portable package; and can be designed to protect unstable medications or disguise unpalatable ingredients. Coatings can be coloured or stamped to aid tablet recognition. Manufacturing processes and techniques can provide tablets special properties; for example enteric coatings or sustained release formulations.
Pharmaceutical Validation
Some drugs may be unsuitable for administration by the oral route. For example protein drugs such as insulin may be denatured by stomach acids; such drugs cannot be made into tablets. Some may be deactivated by the liver (the "first pass effect") making them unsuitable for oral use. However, drugs which can be taken sublingually bypass the liver and are less susceptible to the first pass effect. Bioavailability of some drugs may be low due to poor absorption from the gastric tract; such drugs may need to be given in very high doses or by injection. For drugs that need to have rapid onset, or have severe side effects the oral route may not be suitable. For example Salbutamol can have effects on the heart and circulation if taken orally; these effects are greatly reduced by inhaling smaller doses direct to the required site of action.

Pharmaceutical Process Validation
Tablet properties
Tablets can be made in virtually any shape, although requirements of patients and tabletting machines mean that most are round, oval or capsule shaped. More unsusual shapes have been manufactured but patients find these harder to swallow, and they are more vulnerable to chipping or manufacturing problems.

Tablet diameter and shape are determined a combination of a a set of punches and a die. This is called a station of tooling. The thickness is determined by the amount of tablet material and the position of the punches in relation to each other during compression. Once this is done, we can measure the corresponding pressure applied during compression. The shorter the distance between the punches, thickness, the greater the pressure applied during compression, and sometimes the harder the tablet. Tablets need to be hard enough that they don't break up in the bottle, yet friable enough that they disintegrate in the gastric tract.

The tablet is composed of the Active Pharmaceutical Ingredient (that is the active drug) together with various excipients. These are biologically inert ingredients which either enhance the therapeutic effect or are necessary to construct the tablet. The filler or diluent (eg lactose or sorbitol)is a bulking agent, providing a quantity of material which can accurately be formed into a tablet. Binders eg methyl cellulose or gelatin) hold the ingredients together so that they can form a tablet. Lubricants (eg magnesium stearate or polyethylene glycol) are added to reduce the friction between the tablet and the punches and dies so that the tablet compression and ejection processes are smooth. Disintegrants (eg starch or cellulose) are used to promote wetting and swelling of the tablet so that it breaks up in the gastro intestinal tract; this is necessary to ensure dissolution of the API. Superdisintegrants are sometimes used to greatly speed up the disintegration of the tablet. Additional ingredients may also be added such as coloring agents, flavoring agents, and coating agents. Formulations are designed using small quantities in a laboratory machine called a Powder Compaction Simulator. This can prove the manufacturing process and provide information for the regulatory authorities.this website www,tabletsindia,blogspot,com is dedicated for educting pharmaceuticle students
Pharma process validation

Tablet Excipient:tablets dosage form advantages and disadvantages

Tablets dosage form Excipient
An excipient is an inactive substance used as a carrier for the active ingredients of a medication. In many cases, an "active" substance (such as aspirin) may not be easily administered and absorbed by the human body; in such cases the substance in question may be dissolved into or mixed with an excipient. Excipients are also sometimes used to bulk up formulations with very potent active ingredients, to allow for convenient and accurate dosage. In addition to their use in the single-dosage quantity, excipients can be used in the manufacturing process to aid in the handling of the active substance concerned.

Depending on the route of administration, and form of medication, various excipients may be used. For oral administration, see Tablet and Capsule. For rectal administration see suppository.
Pharmaceutical Validation
Often, once an active ingredient has been purified, it cannot stay in purified form for long. In many cases it will denature, fall out of solution, or stick to the sides of the container. To stabilize the active ingredient, excipients are added, ensuring that the active ingredient stays "active", and, just as importantly, stable for a sufficiently long period of time that the shelf-life of the product makes it competitive with other products. Thus, the formulation of excipients in many cases is considered a trade secret.
Pharmaceutical Process Validation
Pharmaceutical codes require that all ingredients in drugs, as well as their chemical decomposition products are identified and guaranteed to be safe. For this reason, excipients are only used when absolutely necessary and in the smallest amounts possible.
tablets dosage form advantages and disadvantages
.Pharma .blogspot.com

Tabletting formulations

In the tablet-pressing process, it is important that all ingredients be fairly dry, powdered or granular, somewhat uniform in particle size, and freely flowing. Mixed particle sized powders can segregate due to operational vibrations, which can result in tablets with poor drug or active pharmaceutical ingredient (API) content uniformity. Content uniformity ensures that the same API dose is delivered with each tablet.
Pharmaceutical Validation
Some APIs may be tableted as pure substances, but this is rarely the case; most formulations include excipients. Normally, an inactive ingredient (excipient) termed a binder is added to help hold the tablet together and give it strength. A wide variety of binders may be used, some common ones including lactose powder, dibasic calcium phosphate, sucrose, corn (maize) starch, microcrystalline cellulose and modified cellulose (for example hydroxymethyl cellulose).

Often, an ingredient is also needed to act as a disintegrant that hydrates readily in water to aid tablet dispersion once swallowed, releasing the API for absorption. Some binders, such as starch and cellulose, are also excellent disintegrants.
Pharma process validation
Small amounts of lubricants are usually added, as well. The most common of these is magnesium stearate; however, other commonly used tablet lubricants include stearic acid (stearin), hydrogenated oil, and sodium stearyl fumarate. These help the tablets, once pressed, to be more easily ejected from the die.

Friability is an important factor in tablet formulation to ensure that the tablet can stay intact and withhold its form from any outside force of pressure. Wo is the original weight of the tablets, and Wf is the final weight of the tablets after the collection is put through the friabilator.Pharmaceutical Process Validation


Usually < 0.8% friability is considered satisfactory.this website www tablets dosage form.blogspot.com is dedicated for educting pharmaceuticle students

.Pharma .blogspot.com

Sustained Release Dosage Forms

Sustained Release Dosage Forms
Another form of coating is enteric coated tablets which are coated with a material which will dissolve in the intestine but remain intact in the stomach. Polymeric acid compounds have been used for this purpose with some success. This topic and the area of sustained release products has been discussed in more detail in other courses. also see pharmaceutical validation
Benefits

for short half-life drugs, sustained release can mean less frequent dosing and thus better compliance.
reduce variations in plasma/blood levels for more consistent result.
Problems

More complicated formulation, may be more erratic in result. A sustained release product may contain a larger dose, i.e. the dose for two or three (or more) 'normal' dosing intervals. A failure of the controlled release mechanism may result in release of a large toxic dose.
more expensive technology also see validation
Types of products

erosion tablets
waxy matrix
matrix erodes or drug leaches from matrix
coated pellets
different pellets (colors) have different release properties
coated ion exchange
osmotic pump
insoluble coat with small hole. Osmotic pressure pushes the drug out at a controlled rate.
Results - reduced side effects,this website www,tablets dosage form,blogspot,com is dedicated for educting pharmaceuticle students, also see process validation

Tablet Dosage Forms

Tablet Dosage Forms
The tablet is the most commonly used oral dosage form. It is also quite complex in nature. The biggest problem is overcoming the reduction in effective surface area produced during the compression process. One may start with the drug in a very fine powder, but then proceeds to compress it into a single dosage unit.
Ingredients
Tablet ingredients include materials to break up the tablet formulation.

Drug - may be poorly soluble, hydrophobic
Lubricant - usually quite hydrophobic
Granulating agent - tends to stick the ingredients together
Filler - may interact with the drug, etc., should be water soluble
Wetting agent - helps the penetration of water into the tablet
Disintegration agent - helps to break the tablet apart
Coated tablets are used to mask an unpleasant taste, to protect the tablet ingredients during storage, or to improve the tablets appearance. Another barrier is placed between the solid drug and drug in solution. This barrier must break down quickly or it may hinder a drug's bioavailability.
Also see pharmaceutical validation
Disintegration
Disintegration time is the time to pass through a sieve while agitated in a specified fluid. Indicates the time to break down into small particles. Not necessarily solution. In the process of tablet manufacturer the drug is often formulated into a granular state (that is small but not fine) particles. This is done as the granule often has better flow properties than the a fine powder and there is less de-mixing leading to better uniformity. The granules are then compressed to produce the tablet. The disintegration test may lead to an end point of tablet to granule only.
Also see Validation
Dissolution
The time is takes for the drug to dissolve from the dosage form. Numerous factors affect dissolution. Thus the dissolution medium, agitation, temperature are carefully controlled. The dissolution medium maybe water, simulated gastric juice, or 0.1M HCl. The temperature is usually 37 degree C. The apparatus and specifications may be found in the U.S.P. The U.S.P. methods are official however there is a wide variety of methods based on other apparatus. These are used because they may be faster, cheaper, easier, sensitive to a particular problem for a particular drug, or developed by a particular investigator.
Dissolution tests are used as quality control to measure variability between batches which maybe be reflected by in vivo performance. Thus the in vitro test may be a quick method of ensuring in vivo performance. Thus there has been considerable work aimed at defining the in vitro/in vivo correlation.
this website www,tabletsindia,blogspot,com is dedicated for educting pharmaceuticle students, pharma process validation

Route of administration Pharmaceuticle Dosage Form

Route of administration Pharmaceuticle Dosage Form
In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body.

Obviously, a substance must be transported from the site of entry to the part of the body where its action is desired to take place (even if this only means penetration through the stratum corneum into the skin). However, using the body's transport mechanisms for this purpose can be far from trivial. The pharmacokinetic properties of a drug (that is, those related to processes of uptake, distribution, and elimination) are critically influenced by the route of administration.
Classification
Routes of administration can broadly be divided into:

topical: local effect, substance is applied directly where its action is desired
enteral: desired effect is systemic (non-local), substance is given via the digestive tract
parenteral: desired effect is systemic, substance is given by other routes than the digestive tract
The U.S. Food and Drug Administration recognizes 111 distinct routes of administration. The following is a brief list of some routes of administration. also see pharmaceutical validation

Topical
epicutaneous (application onto the skin), e.g. allergy testing, typical local anesthesia
inhalational, e.g. asthma medications
enema, e.g. contrast media for imaging of the bowel
eye drops (onto the conjunctiva), e.g. antibiotics for conjunctivitis
ear drops - such as antibiotics and corticosteroids for otitis externa
intranasal route (into the nose), e.g. decongestant nasal sprays
vaginal, e.g. topical estrogens, antibacterials

Enteral
Enteral is any form of administration that involves any part of the gastrointestinal tract:

by mouth (orally), many drugs as tablets, capsules, or drops
by gastric feeding tube, duodenal feeding tube, or gastrostomy, many drugs and enteral nutrition
rectally, various drugs in suppository or enema form

Parenteral by injection or infusion , also see pharma process validation
intravenous (into a vein), e.g. many drugs, total parenteral nutrition
intraarterial (into an artery), e.g. vasodilator drugs in the treatment of vasospasm and thrombolytic drugs for treatment of embolism
intramuscular (into a muscle), e.g. many vaccines, antibiotics, and long-term psychoactive agents
intracardiac (into the heart), e.g. adrenaline during cardiopulmonary resuscitation (no longer commonly performed)
subcutaneous (under the skin), e.g. insulin
intraosseous infusion (into the bone marrow) is, in effect, an indirect intravenous access because the bone marrow drains directly into the venous system. This route is occasionally used for drugs and fluids in emergency medicine and paediatrics when intravenous access is difficult.
intradermal, (into the skin itself) is used for skin testing some allergens, and also for tattoos
intrathecal (into the spinal canal) is most commonly used for spinal anesthesia and chemotherapy
intraperitoneal, (infusion or injection into the peritoneum) e.g. peritoneal dialysis

Other parenteral
transdermal (diffusion through the intact skin), e.g. transdermal opioid patches in pain therapy, nicotine patches for treatment of addiction
transmucosal (diffusion through a mucous membrane), e.g. insufflation (snorting) of cocaine, sublingual nitroglycerine, buccal (absorbed through cheek near gumline), vaginal suppositories
inhalational, e.g. inhalational anesthetics , also see process validation in pharma

Other
epidural (synonym: peridural) (injection or infusion into the epidural space), e.g. epidural anesthesia
intravitreal
Advantages and disadvantages
There are advantages and disadvantages to each route of administration

Inhalation
Advantages

Fastest method, 7-10 seconds for the drug to reach the brain
User can titrate (regulate the amount of drug they are receiving)
Disadvantages

Most addictive route of administration because it hits the brain so quickly
Difficulties in regulating the exact amount of dosage
Patient having difficulties in giving themselves a drug by inhaler
Injection
Injection incompasses intravenous (IV), intramuscular (IM), and subcutaneous (subcu)

Advantages

Fast: 15-30 seconds for IV, 3-5 minutes for IM and subcutaneous
One injection can be formulated to last days or even months, ex. Depo-Provera is a birth control shot that works for three months
IV can deliver continuous medication, ex. Morphine for patients in continuous pain, or saline drip for people needing fluids
Disadvantages

Because it's fast, there is more risk of addiction when it comes to injecting drugs of abuse
If needles are shared, there is risk of HIV and other infectious diseases
It is the most dangerous route of administration because it bypasses most of the body's natural defenses, exposing the user to health problems such as hepatitis, abscesses, infections, and undissolved particles or additives
If not done properly, air boluses (bubbles) can occur and can be fatal
Need of strict asepsis
Uses
Some routes can be used for topical as well as systemic purposes, depending on the circumstances. For example, inhalation of asthma drugs is targeted at the airways (topical effect), whereas inhalation of volatile anesthetics is targeted at the brain (systemic effect).
----Ad--pharma guideline
On the other hand, identical drugs can produce different results depending on the route of administration. For example, some drugs are not significantly absorbed into the bloodstream from the gastrointestinal tract and their action after enteral administration is therefore different from that after parenteral administration. This can be illustrated by the action of naloxone (Narcan), an antagonist of opiates such as morphine. Naloxone counteracts opiate action in the central nervous system when given intravenously and is therefore used in the treatment of opiate overdose. The same drug, when swallowed, acts exclusively on the bowels; it is here used to treat constipation under opiate pain therapy and does not affect the pain-reducing effect of the opiate.

Enteral routes are generally the most convenient for the patient, as no punctures or sterile procedures are necessary. Enteral medications are therefore often preferred in the treatment of chronic disease. However, some drugs can not be used enterally because their absorption in the digestive tract is low or unpredictable. Transdermal administration is a comfortable alternative; there are, however, only a few drug preparations are suitable for transdermal administration. Validation

In acute situations, in emergency medicine and intensive care medicine, drugs are most often given intravenously. This is the most reliable route, as in acutely ill patients the absorption of substances from the tissues and from the digestive tract can often be unpredictable due to altered blood flow or bowel motility.
Technorati Profile

Manufacture of Pharmaceutical Tablet Coatings

Manufacture of Pharmaceutical Tablet Coatings:-
Today here we will briefly go through Tablets coating issues
Advantages and Process and the Problem and their Solutions
A typical method of dispersion is as follows:• The water/solvent is charged into the mixing vessel, with the mixer positioned off
center to create a vortex.
• The dry ingredients are added and drawn into the vortex.
• Mixing continues until the ingredients are fully dissolved.
• The finished coating is applied to the tablets by spraying in coating pans.
In order to achieve the above, a number of processing factors must be considered:
• The mixer must be capable of circulating the entire contents of the vessel to ensure
uniformity.
• A wide range of colors are used in tablet coatings, and batch sizes are generally small.
• Equipment must be easily cleaned and ideally adapted to be cleaned in place (CIP).
• The mixer must be capable of processing at ambient temperatures as some
ingredients may be heat sensitive.
Pharmaceutical tablets are given a coating for a number of reasons:
• To improve the appearance and aid identification.
• To protect the tablet from moisture and other adverse conditions.
• To lubricate the tablet to ease swallowing.
• To disguise unpleasant tastes.
• To create a barrier between the active ingredient and the gastrointestinal tract.
• To control the release of drug into the body.
Coatings generally consist of a sugar or cellulose based binder, plasticizer, film forming
agent and colorant.These are supplied in granulated or powder form for dispersion in
aqueous or organic solvents at concentration varying from 10 -20% depending on the
desired properties and formula.
The Process
Manufacture of Pharmaceutical Tablet Coatings
Whilst many proprietary coatings are designed to be easily dispersed, a number of
problems are frequently encountered when using conventional mixers and agitators:
• Conventional agitators cannot rapidly dissolve materials at ambient temperatures.
• Agitators are not capable of rapidly breaking down agglomerates.
• A low particle size is required in order to avoid clogging of the spraying
apparatus.
• If the colorant is not properly dispersed, flecks of color can occur in the tablets.
A high shear mixer can overcome all of these manufacturing difficulties. The
rotor/stator work head is capable of dissolving sugar and dispersing cellulose type
materials in a fraction of the time taken by conventional agitators, operating as follows:
The Solution
This develops a circulatory pattern of mixing within the (see also pharmaceutical validation)
vessel which ensures that all material passes through the
work head many hundreds of times, quickly dissolving the
granules into the liquid and progressively reducing the particle size. This is achieved without the need for raised temperatures.
The granules are milled by the intense action provided by
the rotor/stator work head.Agglomerates are broken down
and dispersed.The materials are then forced out through
the stator into the body of the mix. Fresh liquid and
powdered ingredients are drawn into the work head.
The vessel is charged with the base liquid.The mixer is
started and the coating granules and other ingredients are
added.The high speed rotation of the rotor creates a
powerful suction which draws the granulated or powdered
coating material and liquid into the work head. They are
rapidly mixed and driven towards the periphery of the
work head by centrifugal force pharma process validation
The Problem
• Consistent product quality and repeatability.
• Agglomerate-free mix.
• Rapid mixing time.
• Maximized yield of raw materials as thickening agents are fully hydrated and other
ingredients fully dispersed.
The batch size, formulation, type of ingredients and the viscosity of the end product dictate
The Advantages
A In-Line Mixer Agitator for in-tank uniformity
Pipeline return below fluid
level to prevent aeration
High Shear Batch Mixers.
• Suitable for batch sizes up to 400 gallons.
• Can be used on mobile floor stands.
• Sealed units available for pressure/vacuum operation.
• Small units available for R&D and pilot production.
High Shear In-Line mixers.
• Ideal for larger batches
• Aeration-free
• Easily retro fitted to existing plant
• Self pumping
• Can be used to discharge vessel
• Ultra Hygienic models available
Bottom Entry Mixer Stirrer/Scraper Unit
High Shear Bottom Entry mixers.
• Suitable for use on high viscosity products in
conjunction with an anchor stirrer/scraper
• Ultra Hygienic
----Ad--pharmaguideline

tablets dosage form advantages and desadvantages