Coating of tablets and multiparticulates

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Coating of tablets and multiparticulates

Stuart C. Porter

Chapter contents

Key points

• Coating, especially film coating, of pharmaceutical tablets and multiparticulates is commonplace.

• Coatings are applied for many reasons, e.g. improving product appearance, making swallowing easier and modifying drug release.

• Pan-coating techniques are usually used for coating tablets, while fluid-bed processes are often preferred for coating multiparticulates.

• Sugar coating is a multi-step, time consuming process, while film coating is generally a faster single-step process.

• Since film coating has become the dominant process used in the global pharmaceutical industry today, the once common use of organic solvents (with their many associated hazards) has been replaced with the preferred use of aqueous coating formulations.

• All coating processes can be considered stressful (in the mechanical sense), thus placing stringent demands on the robustness of the core (the tablets or multiparticulates being coated) to help minimize defects.

Introduction

Coatings may be applied to a wide range of oral solid dosage forms, including tablets, capsules, multiparticulates and drug crystals. While tablets represent the class of dosage form that is most commonly coated, coated multiparticulates are also popular.

Definition of coating

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 that broadly range from facilitating product identification to modifying drug release from the dosage form.

Reasons for coating

The reasons for coating pharmaceutical oral solid dosage forms are quite varied. The more common reasons include (no order of importance implied):

1. Providing a means of protecting the drug substance (active pharmaceutical ingredient; API) from the environment, particularly light and moisture, and thus potentially improving product stability.

2. Masking the taste of drug substances that may be bitter or otherwise unpleasant.

3. Improving the ease of swallowing large dosage forms, especially tablets. Tablets that are coated are considered by patients to be somewhat easier to swallow than uncoated tablets.

4. Masking any batch differences in the appearance of raw materials and hence allaying patient concern over products that would otherwise appear different each time a prescription is dispensed or product purchased (in the case of over-the-counter products).

5. Providing a means of improving product appearance and aiding in brand identification.

6. Facilitating the rapid identification of a product by the manufacturer, the dispensing pharmacist and the patient. In this case, the coatings would almost certainly be coloured. It is important here to emphasize that efficient labelling and associated procedures are the only sure way of identifying a product. However, product colour is a useful secondary check.

7. Enabling the coated product (especially tablets) to be more easily handled on high-speed automatic filling and packaging equipment. In this respect, the coating often improves product flow, increases the mechanical strength of the product and reduces the risk of cross-contamination by minimizing ‘dusting’ problems.

8. Imparting modified-release characteristics that allow the drug to be delivered in a more effective manner.

Types of coating processes

Three main types of process are used in the pharmaceutical industry today:

Film coating is the most popular technique and virtually all new coated products introduced to the market are film coated. Film coating involves the deposition, usually by spraying a liquid coating system, of a thin film of a polymer-based formulation onto the surface of a tablet, capsule or multiparticulate core.

Sugar coating is a more traditional process closely resembling that used for coating confectionery products. It has been used in the pharmaceutical industry since the late 19th century. It involves the successive application of sucrose-based coating formulations, usually to tablet cores, in suitable coating equipment. The water evaporates from the syrup, leaving a thick sugar layer around each tablet. Sugar coats are often shiny and highly coloured.

Compression coating, although traditionally a less popular process, has gained increased interest in recent years as a means of creating specialized modified-release products. It involves the compaction of granular material around a preformed tablet core using specially designed tableting equipment. Compression coating is essentially a dry process.

Each of these processes will now be considered in turn and an overview of relevant coating processes and materials will be given.

Film coating

Film coating is the more contemporary and thus commonly used process for coating oral solid dosage forms. As described above, it involves the application of a thin film to the surface of a tablet, capsule or multiparticulate core. Now all newly launched coated products are film coated rather than sugar coated, often for many of the reasons given in Table 32.1.

Table 32.1

Major differences between sugar and film coating

Features Sugar coating Film coating
Tablets
Appearance Rounded with high degree of polish Retains contour of original core
Usually not as shiny as sugar coat types
Weight increase due to coating materials 30–50% 2–3%
Logo or ‘breaklines’ Not possible Possible
Other solid dosage forms Coating possible but little industrial importance Coating of multiparticulates very important in modified-release forms
Process
Stages Multistage process Usually single stage
Typical batch coating time 8 hours, but easily longer 1.5–2 hours
Functional coatings Not usually possible apart from gastro-resistant (enteric) coating Easily adaptable for controlled release

Types of film coatings

Film coatings may be classified in a number of ways but it is common practice to do so in terms of the intended effect of the applied coating on drug release characteristics. Hence film coatings may be designated as either:

Immediate-release coatings are usually readily soluble in water, while gastro-resistant coatings are only soluble in water at pH values in excess of 5–6 and are intended to either protect the drug while the dosage form is in the stomach (in the case of acid-labile drugs) or prevent release of the drug in the stomach (in the case of drugs that are gastric irritants). More recently, gastro-resistant coatings have been employed as an integral part of colonic drug delivery systems (Alvarez-Fuentes et al 2004). For the most part, extended-release coatings are insoluble in water. They are designed to ensure that the drug is released in a consistent manner over a relatively long period of time (typically 6–12 hours) and thus reduce the number of doses that a patient needs to take in each 24-hour period. Additionally, extended-release film coatings are used to modify drug release in such a way that desired therapeutic benefits can more easily be achieved and thus drug efficacy improved.

Description of the film-coating process

Film coating involves the application of liquid, polymer-based formulations to the surface of the tablets (for the sake of brevity, the term ‘tablet’ will be used here to represent any form of dosage unit that is to be coated). It is possible to use conventional panning equipment but more usually specialized equipment is employed to take advantage of the fast coating times and high degree of automation possible.

The coating liquid (solution or suspension) contains a polymer in a suitable liquid medium, together with other ingredients such as pigments and plasticizers. This solution is sprayed on to a rotating, or fluidized, mass of tablets. The drying conditions employed in the process result in the removal of the solvent, leaving a thin deposit of coating material around each tablet core.

Process equipment

The vast majority of film-coated tablets are produced by a process which involves the atomization (spraying) of the coating solution or suspension on to the surface of tablets.

Modern pan-coating equipment is of the side-vented type (as shown in Fig. 32.1) and some typical examples include:

Manufacturers of units that operate on a fluidized-bed principle include:

Depending on the particular film-coating application involved, fluidized-bed equipment may be further divided into one of the three operating principles shown in Figure 32.2.

The coating formulation is invariably added as a solution or suspension via a spray gun. The design and operation of film-coating spray guns are similar in both perforated-pan and fluidized-bed coaters, although differences in the performance of spray guns provided by different vendors, especially in perforated-pan processes, have been noted (Macleod & Fell 2002). A typical example of spray coating in a pan coater is shown in Figure 32.3.

Film-coating formulations

Currently, the majority of film-coating processes involve the application of a coating liquid where a significant proportion of the main component (the solvent/vehicle) is removed by means of a drying process that is concurrent with the application of that coating liquid. Film-coating formulations typically comprise:

There are certain types of coating process that differ from this common approach. For example, some processes involve the application of hot-melt coatings that congeal on cooling (Jozwiakowski et al 1990), while others take advantage of recent developments in powder application technologies (Porter 1999).

It should be mentioned that all ingredients used in film-coating formulations must comply with the relevant regulatory and pharmacopoeial requirements current in the intended marketing area.

Film-coating polymers

The ideal characteristics of a film-coating polymer are discussed below.

Solubility

Polymer solubility is important for two reasons:

Film coatings that are used on immediate-release products should utilize polymers that have good solubility in aqueous fluids to facilitate the rapid dissolution of the active ingredient from the finished dosage form following ingestion. Such coatings are usually applied as solutions in an appropriate solvent system (with a strong preference being shown for water). However, film coatings used to modify the rate or onset of drug release from the dosage form tend to have limited or no solubility in aqueous media; such coatings are usually applied either as polymer solutions in organic solvents or as aqueous polymer dispersions (discussed later in this chapter).

Viscosity

Viscosity is very much a limiting factor with regard to the ease with which a film coating can be applied. High viscosity (typically that exceeding about 500 mPa s) complicates transfer of the coating liquid from the storage vessel to the spray guns, and subsequent atomization of that coating liquid into fine droplets. Ideally, therefore, polymers applied as solutions in a selected solvent should exhibit relatively low viscosities at the preferred concentration. This will help to facilitate easy, trouble-free spray application of the coating solution, especially in production-scale film-coating equipment.

Permeability

Appropriate permeability (to which the chosen polymer makes a significant contribution) is a key attribute when considering the various functional properties that film coatings are expected to possess. For example, coating permeability is of significant importance when the film coating is intended to:

These properties vary widely between the various polymers that might be considered for film-coating formulations.

Mechanical properties

In order to perform effectively for the purpose intended, a film coating must exist as a discrete, continuous coating around the surface of the product to be coated, and must be free from defects typically caused by the stresses to which the coating is likely to be exposed during the coating process, during packaging and during the subsequent distribution of the final product.

Consequently, film-coating polymers should possess suitable characteristics with respect to: