Film coating: Polymers used in immediate release film coating

Film Coating Process: Polymers Used in Immediate-Release Film Coating

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Coating is a process by which an essentially dry outer layer of coating material is applied to the surface of a dosage form in order to confer specific benefits over uncoated variety. The term immediate-release film coating (also known as ‘non-functional’ film coating or conventional film coating) is used to describe film coatings that are designed to improve product appearance, perhaps improve handling and stability of the dosage form, but has no measurable effect on biopharmaceutical properties of the dosage form.

From this description, it is apparent that esthetics are of great importance, and consequently are likely to influence selection of the raw materials to be used in the coating formulation. This selection is often based on factors that

  1. Affect the mechanical properties (such as tensile strength, elasticity, and adhesion) of the coating
  2. Allow the smoothest, glossiest coatings to be obtained, and
  3. Produce coatings that readily dissolve in the human gastrointestinal tract.

In this article, we will focus on various polymers used in immediate–release film coating.

Ideal characteristics of polymers used in immediate-release film coating

Ideal requirements of polymers used in immediate-release film coating are summarized below:

  1. It should be readily soluble in aqueous media
  2. It should be able to form strong, flexible films
  3. Adhere strongly to tablet surfaces
  4. Capacity to form elegant films
  5. Facilitate ease of processing (pumping, spraying, atomization, and lack of tackiness)
  6. Permit rapid and complete release active drug substance from dosage forms
  7. High compatibility with other coating solution additives
  8. Nontoxic with no pharmacological activity

Read Also: blet Coating Process: Film Coating

Polymers used in immediate-release film-coating formulations

Polymers used in immediate-release coating formulations fall into the following categories

  1. Cellulosic polymers
  2. Vinyl derivatives
  3. Acrylic polymers
  4. Glycols




Cellulosic polymers

This class of polymers are widely used in film-coating pharmaceutical dosage forms, with a popularity that stems from their common usage from the early days of film coating when organic solvents were always used; global regulatory acceptance; ready availability from a number of vendors; and ability to form coatings generally having acceptable properties (such as good film strength and aqueous solubility).

Cellulosic polymers (with the exception of ethylcellulose) have good organic-solvent and aqueous solubility, thus facilitating the transition to aqueous film coating. Examples of cellulosic polymers used in immediate-release coating film coating include:

a. Hydroxypropyl methylcellulose (HPMC)

Hydroxypropyl methylcellulose, also known as hypromellose is a partially methylated and O-(2-hydroxypropylated) cellulose ether derivative that occurs as an odourless and tasteless, white or creamy-white fibrous or granular powder. The fi­rst application of HPMC for ­film coating appeared in a patent by Singiser of Abbott Laboratories in 1962. Film coatings using Hydroxypropyl methylcellulose have become popular, taking the place of the conventional sugar coating of tablets, because

  1. It is readily soluble in both aqueous media and a wide range of organic solvent systems normally used for film coating
  2. It is colourless and can be coloured by the use of pigments or used in the absence of pigments to form clear films
  3. It is relatively easy to process due to its non-tacky nature
  4. It is highly resistant to heat, light and moisture
  5. It gives a superior appearance and
  6. It is relatively cheap.

HPMC is ideal for coating pharmaceutical tablets intended for immediate release as it produces tough, yet flexible films that provide excellent protective barriers for coated substrates. With these properties, film coating with HPMC can increase the stability of the active drug substance, the mechanical integrity of the substrate, and provide a sufficient barrier for taste masking applications; yet is sufficiently soluble in gastric fluid, leading to complete release of the active ingredients.

When used alone, HPMC has tendency to bridge or fill the debossed tablet surfaces. So mixtures of HPMC and other polymers/ plasticizers are used. HPMC is available in several grades that vary in viscosity and extent of substitution. Commercially available HPMC shown below

polymers used in immediate-release film coating: Standards on the Contents of Substituents of HPMC

Standards on the Contents of Substituents of HPMC

The first two digits of the four-digit designation represent the median percentage content of methoxyl groups while the last two represents the median percentage content hydroxypropoxyl groups. The selection of proper substitution type is important for some pharmaceutical applications. The substitution affects the solubility–temperature relationship. Among the three grades, 2208, 2906, and 2910, which have long been commercially available worldwide, 2910 has the best solubility in organic solvents, and so it has often been used for organic solvent-based coating. Even though aqueous coating has been replacing solvent-based coating and the solubility in organic solvents is of less importance, the 2910 grade is still widely used. Substitution grades other than 2910 are also applicable for aqueous coating, but there are few suitable commercial products of those substitution grades having low viscosity.

Various problems that arise during aqueous coating using HPMC can be attributed to an improper

coating formulation or processing conditions. Some of the problems include picking, cracking of film coatings, bridging of logos, mottling, orange peel and inter-tablet colour variation.



b. Hydroxypropyl cellulose (HPC)

Hydroxypropyl cellulose is a non-ionic water-soluble and pH-insensitive cellulose derivative produced by the reaction of cellulose with propylene oxide. HPC has similar properties to HPMC with respect to aqueous solubility and general film functionality; however, some key distinctions exist that have limited its use in favour of HPMC.

Films produced from this polymer tend to be rather tacky and thus limits production efficiency. Also, HPC films are more elastic and weaker in tension than HPMC films, and therefore are less resistant to breakage under mechanical stress.

Currently, this polymer is very often used in combination with other polymers to provide additional adhesion to the substrate and to improve flexibility. HPC is commercially available in a variety of grades of varying molecular weight and degrees of substitution. A good example is Klucel (Aqualon, Wilmington, Delaware, U.S.A.).

Read Also: Tablet Coating Process: Sugar Coating

c. Hydroxyethyl cellulose (HEC)

Hydroxyethyl cellulose is a white, yellowish-white or greyish-white, odourless and tasteless, hygroscopic powder obtained by treating alkali cellulose with ethylene oxide. HEC is generally insoluble in organic solvents, and although it was one of the earliest water-soluble cellulose ethers used for film coating applications, its limited solubility in organic solvents restricted its industrial use as drying efficiency was a primary concern.

Just like HPC, films produced from HEC has a tendency to be tacky and this limits production efficiency. Also, films formed from HEC are more elastic and weaker in tension than that formed with HPMC and therefore are less resistant to breakage under mechanical stress.

HEC is most commonly used in conjunction with a primary film coating polymer, such as HPMC, to improve adhesion to the substrate and to improve film flexibility.

HEC is commercially available in the brand names Natrosol® and Cellosize® (Aqualon, Wilmington, Delaware, U.S.A.) with different grades that vary in molecular weights.

d. Methylcellulose (MC)

Methylcellulose is a white to yellowish white, odourless and tasteless fibrous powder or granules synthesized by methylating alkali cellulose with methyl chloride. The degree of substitution of methoxy groups influences the molecular weight, viscosity, and solubility characteristics of MC.

MC is soluble in water and has similar characteristics to HPMC. It is rarely used in film coating possibly because of the lack of commercial availability of low viscosity material meeting the appropriate compendial requirements.

e. Sodium carboxymethyl cellulose (NaCMC)

Sodium carboxymethyl cellulose is the sodium salt of the carboxymethyl ether of cellulose, which occurs as a white to almost white, odourless, tasteless, granular powder. It is formed by natural cellulose modification as a kind of cellulose derivate with an ether structure.

Sodium carboxymethyl cellulose is easily dispersed in water to form colloidal solutions but it is insoluble in most organic solvents and hence not a material of choice for coating solution based on organic solvents. Films prepared by it are brittle but adhere well to tablets. Partially dried films of NaCMC are tacky. So coating compositions must be modified with additives. NaCMC-based fi­lms have low oxygen permeability but relatively high water vapour permeability.

Vinyl derivatives

These include;

a. Polyvinyl pyrrolidone (PVP)

Polyvinyl pyrrolidone, also commonly called povidone or polyvidone is the most common vinyl polymer used in the pharmaceutical industry today. It is a fine, white to creamy-white coloured, odourless or almost odourless, hygroscopic powder obtained by free radical polymerization of vinylpyrrolidone in water or 2-propanol (isopropanol), yielding a chain structure of vinylpyrrolidone.

PVP is used in film coatings due to its potentially high film-adhesion characteristics. Unfortunately, its use in film coating of pharmaceutical formulations is limited because of its inherent tackiness(both during application of the coating and on final coated product). Polyvinyl pyrrolidone also produces coatings that tend to be somewhat brittle and hygroscopic.

b. Polyvinyl pyrrolidone-polyvinyl acetate copolymers

Polyvinyl pyrrolidone-polyvinyl acetate copolymer is a white powder produced by polymerisation of the monomers N-vinyl-2-pyrrolidone (NVP) and vinyl acetate (VA). It potentially has greater utility than the homopolymer because it is less tacky.

Polyvinyl pyrrolidone-polyvinyl acetate copolymer produces films that exhibit good adhesion characteristics and generates coating solutions with low viscosities.

c. Polyvinyl alcohol (PVA)

Polyvinyl alcohol occurs as an odourless, white to cream-coloured granular powder by produced through the hydrolysis of polyvinyl acetate. The repeating unit of vinyl alcohol is not used as the starting material because it cannot be obtained in the quantities and purity required for polymerization purposes. The hydrolysis proceeds rapidly in methanol, ethanol, or a mixture of alcohol and methyl acetate, using alkalis or mineral acids as catalysts.

Polyvinyl alcohol has gained popularity recently as an immediate-release film-coating polymer because of its good film properties, and the relatively low viscosity of its coating solutions. Typical characteristics of coatings made with this polymer include the fact that coating solutions that can be somewhat tacky, while subsequent dry films tend to exhibit good adhesion properties (to tablet surfaces) and excellent barrier properties (to environmental gases such as oxygen and water vapour); however, applied coatings may, under certain circumstances, slightly retard tablet dissolution behaviour.




d. Polyvinyl alcohol-polyethylene glycol copolymers

This is a synthetic polymer that is mainly used in immediate-release film coating of pharmaceutical dosage forms. It is a hydrophilic freely water-soluble polymer, consisting of approximately 75% vinyl alcohol units and 25% ethylene glycol units. Polyvinyl alcohol-polyethylene glycol copolymer is produced by grafting polyvinyl acetate onto a backbone of polyethylene glycol followed by hydrolysis of the polyvinyl acetate side chains to form polyvinyl alcohol grafted side chains.

Polymers used in immediate-release film coating: Structure of Polyvinyl alcohol-polyethylene glycol copolymers

Structure of Polyvinyl alcohol-polyethylene glycol copolymers

Film coatings formed from Polyvinyl alcohol-polyethylene glycol copolymers are less tacky than traditional polyvinyl alcohol coatings. It also has additional benefit of being extremely flexible, thus improving film robustness and allowing greater expansion capabilities should the tablet cores expand slightly during the coating process.

Acrylic polymers

These comprise a group of synthetic polymers with diverse functionalities in film coating. They can be used for immediate-release coatings, taste and odour masking, coloured or transparent coatings, etc.

Acrylic polymers are available as the Eudragit® products from Röhm Pharma. Only Eudragit® E, (a cationic co-polymer) is freely soluble in gastric fluid up to pH 5 and expandable and permeable above pH 5.

Glycols

Polyethylene glycols

PEG is a common abbreviation for polyethylene glycol – or, more properly, poly (ethylene glycol) – which refers to a chemical compound (or water-soluble synthetic polymer) composed of a repeating chain of ethylene oxide (CH2CH2O)x. It is formed by the reaction of ethylene oxide and water under pressure in the presence of a catalyst.

Polyethylene glycols have not been popular as the major polymer in film-coating formulations because its films are waxy, hygroscopic, and soften readily at only moderately elevated temperatures. The lower molecular grades of PEG (200-600) tend to be more appropriately used as plasticizers in aqueous film coating.

References

  • Avis, K., Shukla, A. and Chang, R. (1998). Pharmaceutical Unit Operations: Coating London, Taylor & Francis Group, LLC.
  • Cole, G. (2002). Pharmaceutical Coating Technology. UK, Taylor & Francis Ltd.
  • Felton, L. (2017). Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms (4th). New York: Taylor & Francis Group, LLC.
  • http://www.fao.org/fileadmin/user_upload/jecfa_additives/docs/monograph17/additive-542-m17.pdf
  • Lieberman, H., Lachman, L. and Schwartz, J. (1990). Pharmaceutical Dosage Forms: Tablets. New York: Marcel Dekker, Inc.

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