Various Polymer Use In Pharmaceutical Application And Polymer Coating
Shridhar J Pandya
Tablets are by far the most popular dosage form when administering drugs to patients, and a large proportion of the tablets produced around the world are film coated. With the current awareness of health, safety and environmental problems, film coating is a process that is routinely employed in the preparation of pharmaceutical solid dosage forms.
The success of coating process is determined by three factors: formulation of the coating system, coating process parameters and tablet core. During the last 20 years, there has been significant research into coating formulations and processes.
It has been used extensively in the pharmaceutical industry, e.g. for the application of non-functional or functional coats (aesthetic, protective or rate controlling polymer films) and for the deposition of Active Pharmaceutical Ingredients (APIs) onto nonpareils (multi-particulate dosage forms).
An accurate method of coating objects 3 to 30 mm in length with APIs is also desired in the pharmaceutical industry as this is the size range of most single-unit solid dosage forms. These include tablets for oral administration and forms for other methods of delivery including human implantation.
Existing methods of coating objects in this size range have limitations, e.g. in terms of coating speed and accuracy / uniformity, particularly for the deposition of low dose API onto single unit tablet dosage forms which requires a greater degree of accuracy than can be achieved using current tablet coating techniques1.
A novel method of coating small objects has been developed that has demonstrated the ability to uniformly coat inert objects of sizes between 3 and 30 mm in length with a high degree of accuracy. Using the coating method, Relative Standard Deviations (RSDs) below 2% have been achieved for total coating contents as low as 200 micrograms per object. However, it is unknown how accurately the deposition will be on conventional pharmaceutical tablets (which have a higher degree of friability and more irregular surface compared to the inert objects used).
Tablet Coating Applications:
The application of coating of tablets, which is an additional step in the manufacturing process, increases the cost of the product. Therefore, the decision to coat a tablet is usually based on one or more of the following objectives:
- To mask the taste, odor, color of the drug.
- To provide physical and chemical protection for the drug.
- To control the release of the drug from the tablet.
- To protect the drug from the gastric environment of the stomach with an acid resistant enteric coating.
- To incorporate another drug or formula adjuvant in the coating to avoid chemical incompatibilities or to provide sequential drug release.
- To improve the pharmaceutical elegance by use of special colors and contrasting
Primary Components Involved In Tablet Coating
There are three primary components involved in tablet coating:
ØParameters of the coating process
ØFacility and ancillary equipment
ØAutomation in coating process
1. Tablet Properties –
The benefits of film coating more than justify the exposure of the product to the rigor of the coating process, during which the tablets (and the applied coating) are constantly subjected to mechanical stress along with conditions of elevated temperature and humidity. Therefore, cores must be designed using more stringent criteria compared with uncoated dosage forms to guarantee a product robust enough to withstand the additional stress imparted by the film coating process.
The design (properties) of such a substrate (tablet) should be:
- The tablets must be resistant to abrasion and chipping, which is caused by the intense attrition of the tablets striking other tablets or walls of the coating equipment during the coating process.
- Tablet surfaces that are brittle, that soften in the presence of heat, or that are affected by the coating composition tend to become rough in early phase of the coating process and are unacceptable for film coating.
- Films coatings adhere to all exposed surfaces, so that any surface imperfection is coated is not eliminated. The quality of thin film coatings applied to compressed tablets usually depends much more on the quality of the starting tablet than on the quality of the time at which sugar coatings are applied.
- In addition to a smooth surface, the physical shape of the tablet is important. The ideal shape for coating is a sphere, which allows tablets to roll freely in the coating pan, with minimal tablet-to-tablet contact. The worst shape is a square flat-faced tablet, in which case coating materials would collect between the surfaces to glue them together. For this reason, coated tablets have rounded surfaces, the more convex the surface is, and the fewer difficulties will be encountered with tablet agglomeration.
- For the coating to adhere to the tablet, the coating composition must wet the surface. The surface properties of the tablet depend on the chemical nature of the ingredients utilized in the formulation. Hydrophobic tablet surfaces are difficult to coat with aqueous-based coatings that do not wet the surface.
Figure1: Indentation hardness profiles for tablets of different shape.
Figure 1 shows the surface hardness across the crown of differently shaped tablets1. Flat faced and shallow concave tablets have relatively high overall surface hardness, but tend to be brittle at the edges. The deep concave and ball shaped tablets have good mixing characteristics, but offer the lowest levels of mechanical strength, particularly at the crown. Flat, shallow/deep concave, ball/caplet-shaped tablets are not the best choice for film coating.
Fig:1 Areas prone to surface erosion for (A) flat, shallow concave, caplet shaped and (B) deep concave tablets.
Figure 2. Illustrates areas on the tablet that have the highest erosion potential. Therefore, normal concave is the preferred shape for film coating.
During critical stages of the drying process, usually immediately after deposition of the coating onto the tablet surface, coating systems become extremely viscous and adhesive. As a result, if tablets exhibit large areas of relative ‘flatness’ on their surfaces, it is possible for them to become bonded together. This situation is prevalent when attempting to coat flat-faced or caplet-shaped tablets (Figure 3).
Remedy: Placing even a very subtle amount of curvature on an otherwise flat surface can minimize twinning problems.
Figure3: Twining during the coating process for (a) flat-faced and (b) caplet-shaped tablets.
Twinning occurs twinning less likely
Flat side adhere slight curvature
More readily limits contact.
2. Coating Process-
The principles of tablet coating are relatively simple.
ØTablet coating is the application of a coating composition to a moving bed of tablets with the concurrent use of heated air to facilitate evaporation of the solvent.
ØThe distribution of the coating is accomplished by the movement of the tablets either perpendicular (coating pan) or vertical (air suspension) to the application of the coating composition.
3. Equipments –
Various techniques can be used to improve coating uniformity. A study suggested that shallow bed depths, a large number of spray guns, and fully optimized baffle systems produce the best coating.
There are generally four types of ‘uniformity’ in manufacturing –
Øuniformity within the product’s life cycle
Øuniformity within a batch
Øuniformity at various dose levels
Øuniformity of individual pellets, Most coating processes use one of the three general types of equipment :
1.Standard coating pan
2.Perforated coating pan
3.Fluidized bed (air suspension) coater
Generally, more energy efficient, automated systems are preferred, to shorten the total coating time and reduce operator participation in the coating process.
Standard/ Conventional Pan System:
ØThe standard coating pan consists of a circular metal pan mounted angularly on a stand.
ØThe pan is 8 to 60 inches in diameter and is rotated on its horizontal axis by a motor.
ØHeated air is directed into the pan and onto the tablet bed surface and is exhausted by means of ducts positioned through the front of the pan.
ØCoating solutions are applied to the tablets by ladling or spraying the material on to the rotating tablet bed.
ØUse of atomizing system to spray the liquid coating material on to the tablets produce a faster, a more even distribution of the solution or suspension.
Perforated Pan Systems-
Ø All the equipments of this type consist of a perforated or partially perforated drum that is rotated on its horizontal axis in an enclosed housing.
Fluidized Bed (Air Suspension) Systems-
ØFluidized bed coaters are also highly efficient drying systems.
ØFluidized of the tablet mask is achieved in a columnar chamber by the upward flow of drying air.
ØThe air flow is controlled so that more air enters the center of the column, causing the tablets to rise in the center.
ØThe movement of the tablets is upward through the center of the chamber. They then fall towards the chamber wall and move downwards to reenter the air stream at the bottom of the chamber.
Ø In some units, a smaller column(s) is used to direct the tablet movement within the main column.
ØCoating solutions are continuously applied from a spray nozzle located at the bottom of the chamber or are sprayed on to the top of the cascading tablet bed by nozzles located in the upper region of the chamber.
ØTablet cores that are friable and prone to chipping and edge abrasion may be difficult to coat even under optimum conditions in the fluidized bed system, owing to the relatively rough table-to-tablet impact and tablet-chamber contact.
Ø The consequences of non-uniform coating include visual defects such as variations in appearance as well as variations in functionality such as drug-release performance and stability.
Surface Effects In Film Coating:
This includes the process (wetting) which occurs at the interface between the droplets of coating liquid and the surface of the substrate cores-
True wetting is defined as the replacement of a solid-air interface with a solid-liquid interface. During this process, individual gas and vapor molecules must be removed from the surface of the solid and replaced by solvent molecules. This process is influenced by the two properties of wetting power and wettability.
“Wetting power” can be defined as the ability of the atomized droplet to wet the substrate and “wettability” can be defined as the ability of the substrate to be wetted by the atomized droplets.
The processing parameters for coating can be divided into two groups-
Four independent variables have a direct effect on the quality of the coated tablet-
ØInlet drying air volume
ØInlet air temperature
ØSpray atomizing temperature
The objective must be to obtain a satisfactorily coated tablet with the minimum coating time.
These are the variables that result from the value of the settings for the independent variables.
ØDew point of exhaust air
ØOutlet air temperature
ØTablet bed temperature
Types Of Coating:
The pharmaceutical process of sugar coating remains a widely practices technology.Unlike film coating, sugar coating is still a multistep process. Its use of labour is more intensive than in film coating and process operators require a fair degree of skill.
In suitable sugar- coating equipment, the tablet cores are successively treated with aqueous sucrose solutions which, depending on the stage of the coating reached, may contain other functional ingredients e.g. fillers, colors etc. The build up of coating material is due to transference of coating medium from one tablet to another. Typically a single liquid application will be made which will be allowed to spread over the entire tablet bed utilizing the mixing capability of the particular equipment. At this point, drying, usually in the form of heated air will be used t o dry the application. The whole cycle will then be successively repeated.
In this respect, sugar coating differs from film coating as in this process each tablet passes through a zone of application which is subjected to rapid and continuous drying.
Advantages Of Sugar Coating-
- It utilizes inexpensive and readily available raw materials.
- Constituent raw materials are widely accepted-no regulatory problems.
- Modern simplified techniques have greatly reduced coating times over traditional sugar coating methods.
- No complex equipment or services are required.
- The process is capable of being controlled and documented to meet modern GMP standards.
- Simplicity of equipment and readily availability of raw materials make sugar coating an ideal coating method for developing countries.
- The process is generally not as critical as film coating; recovering and reworking procedures are usually possible.
- For high humidity climates, it generally offers a stability advantage over film coating tablets.
- Results are aesthetically pleasing and have wide consumer acceptability.
- Tablet cores may generally be softer than those demanded by film coating especially those for aqueous film coating.
Stages Of Sugar Coating-
This is an organic solvent-dependent step.
ØIt is necessary to protect the tablet core from the aqueous nature of sucrose applications to follow.
ØIt also prevents certain types of materials from migrating to the tablet surface and spoiling the appearance, e.g. oils, acids etc.
ØA film of water-impervious polymer is built up using materials such as:
ØShellac has all the advantages of a natural material, the other polymers used tend to be those which have an additional use as enteric-coating materials so that they should be applied only in sufficient quantity to form an efficient seal.
ØA lamination process, whereby an application of dusting power, e.g. talc, is nearly always used.
ØDuring the sugar coating process the increase in weight achieved can be 30-50% of the weight of the original tablet core. Much of the added weight is applied at the subcoating stage. Subcoating serves to confer the tablet core a perfectly rounded aspect.
ØThe ideal shape for sugar coating is a deeply convex core with minimal edges. This condition will obviously require less coating material than where the tablet edge is comparatively thick.
Defects Of Sugar Coating:
As the sugar coating itself is deliberately isolated from the tablet core there is the possibility of much more standardization than in the area of film coating formulae.
1. Cracking And Splitting Of The Sugar Coat-
·CAUSES: Excess residual moisture from the processing.
·REMEDY: To allow sufficient time between individual applications of syrup.
2. Inversion And Stickiness-
ØCAUSE: Presence of inverted sugar which is difficult to dry adequately. It can be encountered if slightly acidic color coating suspensions are maintained at too high a temperature for too long.
ØREMEDY: Low temperature should be maintained.
- Sugar coatings are brittle and are prone to chipping if subjected to an inappropriate mechanical stress.
- Wax collects in the depressions on the rough tablet surfaces on polishing and remains as tiny white spots at the end of the process.
REMEDY:Ensure smooth tablet surface
Facility And Ancillary Processes:
The facility required for any coating operation should be designed to meet the requirements of current Good Manufacturing Practices (GMPs). Adequate space is required not only for the coating equipment, but also for the coating equipment, but also for solution preparation and in–process storage. The specific safety requirement for coating areas depends on the nature of the solvent. Where explosive or toxic concentrations of organic solvent could occur, during either solution preparation or coating operation, electrical explosion-proofing and specialized ventilation are required.
Treatment of the exhaust air from the coating operation may be desired to recover expensive organic solvents or to prevent solvents and particulate allowed in the limits of organic solvent and particulate allowed in the atmosphere. Compliance with the regulations can be extremely expensive and this cost factor should be considered in developing a new coating. A major advantage of totally aqueous based film coating is that all direct and indirect expenses relating to the purchase, handling and envioronmentally acceptable removal of the organic solvent are circumvented.
Other equipment needed is to support the coating operation. Solution preparation requires tanks, filters and mixers. A colloid mill or ball mill may be needed for the homogeneous dispersion of insoluble solids in the liquid coating mixture. Jacketed tanks may be needed for keeping the some solutions at an elevated temperature.
Within last 6 to 8 years, automation has been achieved in sugar coating and film coating systems. Through a series of sensors and regulating devices for temperature, airflow, spray rate and pan speed, a feedback control of the process is maintained. For process automation, the perforated pans are preferred over the old conventional coating pans because of their better efficiency8.
Materials Used In Film Coating:
The coating materials may be a physical deposition of the material in the tablet substrate, or they may form a continuous film with a wide variety of properties depending upon the composition of the coating formulations.
During the last 40 years, wide varieties of polymers have been evaluated and are being used commercially for tablet coating.
Coating materials generally used are-
ØMiscellaneous coating solution components
Mechanism Of Film Formation:
Film formation from an aqueous polymeric dispersion is a complex matter (Bindschaedler et al., 1983: Zhang et al., 1988, 1989). In the wet state, the polymer is present as a number of discrete particles, and these have to come together in close contact, deform, coalescence and ultimately fuse together to form a discrete film. During processing, the substrate surface will be wetted with the diluted dispersion. Water will be lost under the prevailing conditions as water vapor and the polymer particles will increase in proximity to each other. Complete coalescence occurs when the adjacent particles are able to mutually diffuse into one another.
Minimum Film Forming Temperature-
This is the minimum temperature above which formation will take place using individual defined conditions. it is largely dependent on the glass transition temperature (Tg) of the polymer. ( Lechman 1992)
The available film formers are classified into -
1. Enteric Materials-
Enteric coating of pills and compressed tablets has existed for more than a century. These coatings form a subgroup of modified release coatings and are defined as the coatings that resist the action of stomach acids but rapidly breaks down to release its contents once it has passed into the duodenum.
Some of the most important reasons for the enteric coating are as follows:
ØTo protect the acid-liable drugs from the gastric fluid.
Eg: enzymes and certain antibiotics
ØTo prevent gastric distress or nausea due to irritation from a drug.
Eg: sodium salicylate
ØTo deliver drugs intended for local action in the intestines.
Eg: intestinal antiseptics could be delivered to their site of action in a concentrated form and bypass systemic absorption in the stomach.
ØTo deliver drugs that are optimally absorbed in the small intestine to their primary absorption site in their most concentrated form.
ØTo provide a delayed-release component for repeat action tablets.
An ideal enteric coated material should have the following properties:
1.Resistance to gastric fluids.
2.Ready susceptibility to or permeability to intestinal fluids.
3.Compatibility with most coating solution components and the drug substrates.
4.Stability alone and in coating solutions. The films should not change on aging.
5.Formation of a continuous (uninterrupted) film.
8.Ease of application without specialized equipment.
9. Ability to be readily printed or to allow film to be applied to debossed tablets.
MECHANISM: The mechanism by which these polymers function is by a variable pH solubility profile where polymer remains intact at low pH but at a higher pH will undergo dissolution to permit the release of the contents of the dosage form. (SCHROETER 1965)
Some of the commercially available enteric polymers:
- Cellulose acetate phthalate (CAP)
- Acrylate Polymers
- Hydroxypropyl methylcellulose phthalate
- Polyvinyl Acetate Phthalate (PVAP)
2. Non-Enteric Materials
Some of the most commonly used materials by the pharmaceutical industry:
ØHydroxypropyl Methylcellulose, USP
ØEthyl Cellulose, NF
ØSodium Carboxymethylcellulose, USP
Variation in formulation and processing conditions may result in unacceptable quality defects in the film coating. The source of these defects and some of their probable causes are described in the following sections.
1.Sticking And Picking-
ØOverwetting or examples or excessive film tackiness causes tablets to stick to each other or to the coating pan. On drying, at the point of contact, a piece of the film may remain adhered to the pan or to another tablet, giving a “picked” appearance to the tablet surface and resulting in a small exposed area of the core.
ØREMEDY: A reduction in the liquid application rate or increase in the drying air temperature and air volume usually solves this problem. Excessive tackiness may be an indication of a poor formulation.
ØA rough or gritty surface is a defect often observed when coating is applied by a spray.
ØSome of the droplets may dry too rapidly before reaching the tablet bed, resulting in the deposits on the tablet surface of “spray dried” particles instead of finely divided droplets of coating solution.
ØSurface roughness also increases with pigment concentration and polymer concentration in the coating solution.
ØREMEDY: Moving the nozzle closer to the tablet bed and reducing the degree of atomization can decrease the roughness due to “spray drying”.
3. Orange-Peel Effects-
ØInadequate spreading of the coating solution before drying causes a bumpy or “orange-peel” effect on the coating.
ØThis indicates that spreading is impeded by too rapid drying or by high solution viscosity.
ØREMEDY: Thinning the solution with additional solvent may correct this problem.
4. Bridging And Filling-
Ø(i) During drying, the film may shrink and pull away from the sharp corners of an intagliation or bisect, resulting in a “bridging” of the surface. This defect can be so severe that the monogram or bisect is completely obscured. This mainly represents a problem with the formulation.
ØREMEDY: Increasing the plasticizer content or changing the plasticizer can decrease the incidence of bridging.
Ø(ii) Filling is caused by applying too much solution, resulting in a thick film that fills and narrows the monogram or bisect. In addition, if the solution is applied too fast, Overwetting may cause the liquid to quickly fill and be retained in the monogram.
ØREMEDY: Judicious monitoring of the fluid application rate and thorough mixing of the tablets in the pan can prevent filling.
ØWhen coated tablets require further drying in ovens, too rapid evaporation of the solvent from the core and the effect of high temperature on the strength, elasticity and adhesion of the film may result in blistering.
ØREMEDY: Milder drying conditions are warranted in this case.
6. Hazing / Dull Film-
ØThis is sometimes called Bloom.
ØIt can occur when too high a processing temperature is used for a particular formulation.
ØDulling is particularly evident when cellulosic polymers are applied out of aqueous media at high processing temperatures.
ØIt can also occur if the coated tablets are exposed to high humidity conditions and partial salvation of film results.
ØThis problem can be caused by processing conditions or the formulation.
ØImproper mixing, uneven spray pattern and insufficient coating may result in color variation.
ØThe migration of soluble dyes, plasticizers and other additives during drying may give the coating a mottled or spotted appearance.
ØREMEDY: (i) The use of lake dyes eliminates dye migration.
(ii) A reformulation with different plasticizers and additives is the best way to solve film instabilities caused by the ingredients.
ØIt occurs if internal stresses in the film exceed the tensile strength of the film.
ØREMEDY: tensile strength of the film can be increased by Using higher molecular weight polymers or polymer blends.
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Shridhar J. Pandya
Shridhar pandya. completed B.Pharm form TVES College of Pharmacy, faizpur, Jalgaon. Presently he is pursing M.Pharmacy at AISSMS College of Pharmacy, Pune, he is working on “Taste masked formulations of various bitter taste drugs. He also worked on orodispersible tablets of bitter drugs”.
Amit Patel completed B.Pharm form LM College of Pharmacy, ABD. Presently he is pursing M.Pharm at MS Uni. Baroda, he is working on “Nano Suspension’’
Golakiya Nikul. V
Dixit K. Shah