Coating in oral solid dosage form is very common in the pharmaceutical industry today.In this article the author gives an overview of pharmaceutical coating especially of oral solid dosage forms.
Coating in solid dosage forms are mentioned in early Islamic drug literature. Rhazes , Persian physician,well known for his contributions to Islamic medicine, has described coated pills as early as 850 – 923. Earlier coating was used to preserve food for longer periods. Most probably coating in pharmaceutical solid dosage forms might have evolved from the concept of food preservation .
It was in the mid 80’s , the French had developed sugar coated pills though in fact , the concept of bitter- taste masking of medicines with the help of coating was published in a French publication during 1600.
Soon sugar coated pills gained acceptance in the US & Europe. Especially in the US many pharmaceutical companies started manufacturing coated pills as a main part of their product basket.
The process ( Coating Pan system) and the sugar coating equipment remained essentially unchanged for more than 75 years.
It is Abbott Laboratories which manufactured & marketed the first film coating in pharmaceutical oral solid dosage form, in 1953, though in the early 1950’s Dr.Dale Wurster ( Professor – University of Wiscousin) had patented AIR SUSPENSION COATER for Film Coating system.
Today there are many modern and ultra modern technologies available for the best coating process in tablets, pellets, pills, granules and powder. This is due to the continuous process development, research work towards better patient compliance, cost saving, time saving,& long term stability of the drug. Coating is not limited to pharmaceutical industries but also includes various other industries like unani, herbal, nutraceuticals and agrochemicals.
The uses of coating:
● To provide protection ( physico-chemical) for the active drug
● To mask the unpleasant odour of the API
● To mask the bitter taste of the drug
● To control the release of the API
● To protect the drug in acid media (gastric environment) for certain drugs, with an acid resistant enteric coating (Methacrylic acid based copolymers or other conventional material)
Targeted release of the API at certain pH level ( Acrylate base or conventional material)
● To avoid chemical incompatibilities
● To increase elegance, cosmetic look / visual properties) of the final product
● To increase keeping property of tablets
Protect from internal breakage of tablets during transportation or transfer from one place to another.
Coating process depends on the following factors:
● Properties of tablet / pellets / pills / granules / & powders
● Formulation design
● Granule characteristics
● Tablet hardness
● Selection of excipients
● Friability
● Use of Lubricants
● Shape of tablet
● Process:
● Equipment criteria
● Automation – system
● Parameters of process
● Facility & ancillary equipments
● Coating components
● Coating materials ( Film formers / coating property)
Needless to mention that without a right choice of coating material the purpose of coating will not be solved. So, one has to select the right coating material as per the requirement of the specific drug. There are various coating material available (Conventional coating material and advanced (acrylate base ) coating material.
● Film coating material (Conventional, commonly used)
● HPMC
● Methyl Hydroxy Ethyl Cellulose
● Ethylcellulose
● Hydroxypropyl Cellulose
● Povidone
● Sodium Carboxymethyl Cellulose
● Polyethyline Glycols (PEG) – Used in combinations with other ingredients)
Film coating material ( Acrylate polymes, preferred choice)
● DRUGCOAT E 100 (“Amino Methacrylate Copolymer”
● DRUGCOAT E 12.5 (“Amino Methacrylate Copolymer” )
● Amino Methacrylate Copolymers is the right choice as a seal coating/ moisture barrier coating material. It protects the active ingredient from moisture. It provides a better barrier coating. Concentration requires usually lesser as compared to conventional seal coating material. This copolymer can also be ideal to mask the bitter taste of certain API’s (oral solid dosage forms only), as polymer is soluble in gastric fluid up to pH 5.0
● DRUGCOAT E 100: [A series of acrylate polymers is marketed under the trademark of DRUGCOAT, manufactured by Vikram Thermo (India) Ltd, Ahmedabad with cGMP compliance production facility and state of the art R&D & application centre at Chattral, near Ahmedabad, Gujarat.
● DRUGCOAT E 100 is a cationic copolymer based on dimethyl- aminoethyl methacrylate and other neutral methacrylic acid esters. DRUGCOAT E 100 is the only DRUGCOAT material that is freely soluble in gastric fluid up to pH 5.0 and also permeable and expandable above pH 5.0. This material is also available as organic solution in Isopropanol/Acetone (12.5% solution), brand name DRUGCOAT E 12.5 & 30% AQUEOUS DISPERSION.
NDDS: Following criteria are very important for ideal delivery systems of the active drug:
Convenience of dosage, drug delivery at the site of action, possible fewer side effects & last but not least is the cost.
DRUGCOAT RL 100 & RS 100 are copolymers synthesized from acrylic and methacrylic acid esters with a low content of quaternary ammonium groups. These are available in solid form (granules & powders) and compatible in organic solutions. These polymers produce films for the delayed action (pH – independent), preparations. These materials are widely used in Europe, USA and also now in India for sustained release preparation in oral solid dosage forms.
Enteric coating:
Enteric coating of tablets & pills are in use for more than a century. A common problem associated with the retardant type of non pH dependent polymers, which act by mechanical hydrophobicity, is to provide enteric effect. Here the film may be very thick. Due to this, if the dosage form travels too fast through the gastrointestinal tract, solubilization in intestinal fluids may never be achieved.
Why enteric coating?
● To resist in gastric fluid & release above pH 5.0
● To provide a delayed release component for repeat action tablet/ pellets/pills & granules
● To deliver drug in intestine, in the specific site of action and bypass systemic absorption in the stomach
● To prevent gastric distress or nausea due to irritation from a drug
● Enhances stability & perform target delivery
● Characteristics of most suitable enteric coating materials:
● Resistance to gastric fluid
● Compatibility with most coating solution component & API
● Film should not change on aging
● Ease of application
● Smooth & uniform coating for perfect film formation (even for printed or debussed tablet)
● Long term stability of the finished product
● Less consumption of polymer/coating material
● Non-toxic & low costing
● Enteric coating materials (Conventional)
● CAP (Cellulose Acetate Phthalate)
● HPMC-P ( Hydroxypropyl Methylcellulose Phthalate)
● PVAP (Polyvenyl Acetate Phthalate)
● Enteric coating material (Acrylate polymers: preferable))
● Methacrylic acid copolymers ( Type A, B & C) [ Drugcoat ]
Comparision among commonly used EC material:
CAP:
Though CAP has been used as enteric coating material widely for years , it has some major disadvantages, which are as follows:
● Dissolves only above pH 6, may delay in the absorption of the drug
● Due to presence of Phthalate, stability is a major concern as CAP films are susceptible to hydrolytic removal of phthalic & acetic acids, thereby may change in film properties
CAP films are brittle
● Not a long chain molecule, as Phthalate is added on Cellulose acetate.
● CAP is very hygroscopic and relatively permeable to gastric fluid and moisture as well.
● Usually formulated with hydrophobic film forming material ( in solvent system)
● Higher concentration of material required to achieve perfect enteric property
● High cost
HPMC P:
HPMC P is also used for enteric coating by many pharmaceutical houses. There are few common different grades which are commercially available. Though HPMC P is superior to CAP in enteric coating, it also has certain disadvantages .
Few common disadvantages are:
● Dissolves at a lower pH 5.0 to 5.5, ideally it should be above pH 5.5 and above for common enteric use.
● HPMC P films are also brittle
● Not a long chain molecule, as Phthalate is added on HPMC.
● HPMC P is very hygroscopic and relatively permeable to gastric fluid and moisture as well.
● Usually formulated with hydrophobic film forming material ( in solvent system)
● High cost
Though HPMC P polymers are quite stable as compared with CAP due to the absence of labile acetyl groups in the chain, but Methacrylic acid copolymers (DRUGCOAT) having much more advantages and compatibility.
PVAP:
This polymer is similar to HPMC P In stability & pH dependent solubility but available in ready to disperse system
Acrylate polymers:
There are many grades of commercially available enteric acrylic resins [ DRUGCOAT series ] available since years, which are time tested, non toxic, safe and offers huge techno commercial advantages for various pharmaceutical application. Acrylate polymers ( Methacrylic acid copolymers type A, B & C) offers higher solid contents with low viscosity for a smooth spraying system. It needs less amount of diluents. It has advantages of aqueous, hydro alcoholic coating system, in addition to organic system. Due to micronized form of polymers, it requires less quantity to attain perfect enteric coating. the film forming is very smooth & elegant thus offers an aesthetic look. It has uniform film coating and has logo bridging property.The details as follows:
DRUGCOAT L 100: “Methacrylic acid copolymer type A” :
Advantages:
● Anionic copolymer based on methacrylic acid & methyl methacrylate
● Very fine, micronized free flow white powder
● Soluble in intestinal juice from pH 6.0 onwards
● Insoluble in acid & pure water
● No phthalate present, long chain molecule offers better stability
● Offers higher solid content at a less viscous solution for a good spray
● Need less concentration polymer ( usually 4.0 to 5%) of average weight
● Less quantity of solvent ( IPA/Acetone)
DRUGCOAT L 12.5%
● Available in organic solution, features are same like DRUGCOAT L 100, ( available in white free flowing powder form)
● “Methacrylic acid copolymer type C” DRUGCOAT L 100 55
Advantages:
● Anionic copolymer based on methacrylic acid & ethyl acrylate
● Very fine, micronized free flow white powder
● 100% aqueous system in enteric coating
● Cab be used as hydro alcoholic system
● Soluble in intestinal juice from pH 5.5 onwards
● Insoluble in acid but freely soluble in intestinal juice
● No phthalate present, long chain molecule offers better stability
● Offers higher solid content at a less viscous solution for a good spray
● Need less concentration polymer ( usually 4.0 to 5%) of average weight
● Less quantity of DM water required, 20% reconstitution level
● “Methacrylic acid copolymer dispersion” : DRUGCOAT L 30D
● Aqueous dispersion, pH dependent polymer soluble above pH 5.5 for targeted delivery in the duodenum.Well established & time tested product especially in pellets coating system.
Advantages:
● Aqueous dispersion of an anionic copolymer based on Methacrylic acid
● 100% aqueous system in enteric coating
● Can be used as hydro alcoholic system
● Soluble in intestinal juice from pH 5.5 onwards
● Insoluble in acid but freely soluble in intestinal juice
● No phthalate present, long chain molecule offers better stability
● Offers higher solid content at a less viscous solution for a good spray
● Need less concentration polymer ( usually 4.0 to 5%) of average weight
● Less quantity of DM water required
● Ideal for pellets/granules & powder enteric coating
● Huge cost effective as compared to HPMC P /CAP /PVAP
Conclusion:
Convenience, efficacy, safety & economy are the four major criteria one would like to have in ideal drug delivery system / coating system. All those criteria are attainable with the help of suitable choice of acrylate polymers.
More than 55 years now, methacrylic acid copolymers are used by many research scientists, production chemists worldwide. A lot of newer applications have developed in recent years as well as continuous increase in research activities engaged in studies of various acrylate copolymers / methacrylic acid copolymers due to its excellent properties. Needless to mention that it has made outstanding contributions to various pharmaceutical formulations like film coating, aqueous base enteric coating, solvent base enteric coating, masking of bitter taste, moisture barrier coating, seal coating, time controlled release, sustained release and many more.
Thus it is obvious that the DRUGCOAT series hold potential as a versatile and unique polymer for many more customized/ newer applications. Shifting from conventional materials will be more significant in the coming days.
-The author is Managing Director, Vikram Thermo (India) Ltd