problemas en tabletas recubiertas

7/30/2019 Problemas en Tabletas Recubiertas

1/7

C

As Appeared in Tablets & Capsules April 2008 www.tabletscapsules.com

tablet coating

Troubleshooting appearance-related

problems of film-coated tablets

Stuart C. Porter

International Specialty

products

Film coating of tablets is a complex activity replete with oppor-

tunities for problems to occur. This article describes how to trou-

bleshoot potentially serious appearance-related problems byidentifying possible causes. It also describes how to prevent the

problems from occurring.

reating a film-coated product is a very complex pro-

cess that requires synchronizing many interrelated fac-

tors. These include the interactions that need to occur

among 1) the variables associated with the product to becoated (tablet core), 2) the variables associated with the

coating formulation, and 3) the coating process (e.g., the


2/7

nature of the coating pan, the processing air, and the spray-

ing systems used to apply the coating liquid). All these fac-

tors play a strong part in the ultimate success of the coating

operation, thus the need for troubleshooting initiatives.

Figure 1 lays out the complexities of interrelated functions

inherent in a typical film coating operation.

The most prevalent problems that arise during film

coating affect the visual quality of the coated product. Its

thus understandable that visual quality should be themain impetus when troubleshooting the problem.

However, there are other aspects of product quality that

must be considered, including, for example, product

functionality, where problems could affect drug release

and product stability. Other issues may have an impact

on overall cost and process efficiency.

Bear in mind that problems with film-coated products

usually occur on a production scale, after the product has

received regulatory approval and has been commercial-

ized. So whenever possible, the goal is to limit problem

resolution to very small changestypically process

relatedthat will have minimal regulatory impact. While

methods for making small changes have received a good

deal of attention, the approach is not ideal because it is

reactive, not proactive.

Besides, it is not always possible to resolve a problem

by making a small process change. A formulation change

may need to be considered, which is undesirable from a

regulatory standpoint, of course, but may offer the only

path to resolving a particular problem. Hence, the impor-

tance of proactive troubleshooting: If applied before a

coated product goes into production, it may help prevent

production-scale problems that cannot be resolved with

simple adjustments to the coating process.

A complexity of relationships

Again, film coating involves complex interrelation-

ships between three basic areas: the core (typically a

tablet), the coating formulation, and the coating process.

Thus, when problems ensue, they often cannot be attrib-

uted to any one aspect, but may arise for several reasons:

The formulation of the tablet core is not sufficiently

robust to withstand the coating process, which can be

very stressful, particularly when it involves a coating pan,

which is akin to a production-scale friabilator. Needless

to say, designing tablets at the outset that are robustenough to undergo each film coating process is critical.

The coating formulation is not adequate for the

product being coated or for the coating process being

Figure 1

The complexities of film coating

Inlet air

Volume

Temperature

Moisture contentCoating formulation

Volatility

Tackiness

Viscosity

Surface tension

Solids content

Mechanical properties

Exhaust air

Volume

Temperature

Moisture content

Spraying system

Gun design

Air cap design

Fluid nozzle design

Number of guns

Separation between guns

Angle of guns to tablet bed

Distance of guns from tablet bed

Spray rate

Atomizing air pressure and volume

Pattern air pressure and volume

Tablet cores

Size

Shape

Hardness

Friability

Surface roughness

Surface chemistry

Porosity

Coating pan

Pan dimensions

Pan speed

Batch size

Tablet bed porosity

Tablet bed surface area

Mixing baffles Perforated area

Tablet bed temperature

Control system


3/7

used. It is better to determine this before a final com-

mitment is made to a specific coating formulation or

process.

There is little appreciation for how ultimate product

quality is influenced by variations in 1) raw materials,

2) the coating process, or 3) the process conditions.

Poor maintenance, such as incorrect or infrequent

calibration of process monitoring equipment, results in

decision-making based on inaccurate information.Rarely will just one aspect of an overall coating sce-

nario be identified as the main cause of unsatisfactory

results. It just isnt that simple. With nutraceuticals, for

example, it is not uncommon for the tablet core to con-

tain as much as 90 percent active ingredient, and many of

these ingredients are problematic to begin with. Dosing

at this high a percentage also limits the ability to use

excipients to counteract the actives inherent problems.

Tablet size, shape, and robustness can also pose signifi-

cant challenges to film coating if not taken into considera-

tion at the outset. Consider again high-dose nutraceuticals.

Typically, high dosing means that the tablet core is very

large and may be exotically shaped to ease swallowing. Size

and shape alone can pose challenges to applying a film

coating, but the problems of those attributes are com-

pounded when the nutraceutical tablet core is not suffi-

ciently robust.

Identifying problems quickly and correctly

There are two ways to identify problems that may

require troubleshooting: decision trees and pictorial

libraries of common problems.

The decision-tree technique involves answering a

series of yes-or-no questions. In the example presented in

Figure 2, identifying a problem in film coating begins

with the question, Is the problem one of chemical stabil-

ity? A No response leads to the question, Is the prob-

lem associated with the drug release from the dosage

form? In this example, the answer is again No, which

leads to a third question, Is this an appearance problem?

A Yes response leads to questions phrased to identifyappearance problems (Figure 3). And so on.

Decision trees like these, truncated here to save space,

can be quite useful and effective, but it is critical that the

Figure 2

Example of a decision tree for identifying film-coatingproblems

Is problem one of chemical stability?

Is problem associated with drug release from dosage form?

NoYes

No

Is this an appearance problem?

NoYes

Yes

Figure 3

Example of a decision tree for identifying appearance problems

Are holes present? Is adhesion good?

Are cracks present?

Is film rough?

Are intagliations clear?

Is film rough?

Orange peel

Flaking

Other problems

Yes

Yes

No

YesNo

No

No

No

Yes

Bridging

Other problems

Blistering Wrinkling

Yes

Yes


4/7

right questions be asked in order to create the correct

pathway to identifying the problem.

Pictorial determination is more commonly used as an

identifying technique. The grid of images on page 16

shows a typical library of photos depicting past coating

problems. These can be used to identify a new problem

by comparing it with identifiable past problems and

ascertaining similarities.

Once the problem has been identified, the next step is tolook for its root causes. In this particular case, the root

cause resides in one of the three areas critical to film-coated

products: the core, the coating formulation, or the coating

process. Looking into each of these areas will help deter-

mine where the major impact is likely to be and help iden-

tify the easiest change that can be made to resolve the

problem.

Appearance-related problems are relatively easy to

identify because there is immediate visual feedback.

Problems can be found by looking into the coating pan

or by observing tablets as they are being unloaded. Of

course, the tablets can also be subjected to careful inspec-tion. Visual inspection can also help us to judge the mag-

nitude of the problem. Is it just a few tablets in the batch?

Is it a significant amount or even the whole batch? This

immediate feedback provides an opportunity to identify

and quantify the problem.

On the other hand, identifying non-appearance-

related problems, such as those associated with chemical

stability or drug release, is more difficult because often

the existence of the problem is not readily apparent.

Looking at tablets in a coating pan or as they are un -

loaded from a coating pan will not help you identify a

problem with, for example, dissolution. This sort of prob-

lem can only be determined once samples are analyzed in

the laboratory. Resolving these kinds of functional prob-

lems can be quite challenging. Thats why, for the sake of

conciseness, this article focuses on troubleshooting

appearance-related problems.

Formulation and geometry of tablet cores

There are several considerations to take into account

when formulating tablet cores. The first is physical

robustness, which is judged by measuring several attrib-

utes: mechanical strength, friability, resistance to dimen-sional changes (warming of the cores during film coating

could cause them to expand), and film adhesion (how the

core formulation affects the interaction between the core

and the film coating).

Other issues to consider relate to the cores chemical

robustness. What role will amorphous, hydrophilic mate-

rials play in chemical stability? What is the likely impact

of the cores low-melting-point ingredients on the final

quality of the coated tablet?

Another way to improve tablet coating is to under-

stand the influence of commonly used excipients on film

adhesion to tablets. If there is any reason to suspect thatfilm adhesion might be a problem, then consider using

excipients during the formulation process to enhance

adhesion. Table 1 lists several common excipients and

their influence on film adhesion. If a tablet core formula-

tion calls for a high concentration of an active substance

(where the surface energetics are dominated by the

nature of the active itself), excipients that improve adhe-

sion must be included in the formulation.

How a tablet core is designed can have a significant

impact on the success of film coating. Troubleshootingstarts with a look at the geometry of the cores (their

shape and size), which can affect whether or how they

erode during the tumbling process. Their geometry also

affects the way they will mix as they tumble, which influ-

ences the uniformity of coating distribution.

Finally come the issues related to intagliations (logos),

which are placed on the tablet surface using engraved

punches and aid in tablet identification. Early attention to

not only the logo design, but to where its placed on the

tablet surface, may help minimize downstream defects.

Minimizing surface erosion through core designFigure 4 shows two typical tablet shapes. The more

classic tablet shape (upper diagram) has a rather high

Table 1

Influence of excipients on the adhesion of film coatings totablet surfaces

Excipient Measured adhesion (kPa)

Microcrystalline cellulose 65.4 6.3

Sucrose 44.5 7.9

Anhydrous lactose 51.2 4.3

Spray-dried lactose 24.5 2.7

Dextrose 33.5 9.5

Dicalcium phosphate (dihydrate) 29.9 3.4

Figure 4

Minimizing surface erosion through core design

a. Land of tablet is pronounced and edge is almost 90 degrees.

b. Using dual-radius punches minimizes sharp edges, makingtablet more resistant to damage.


5/7

degree of curvature on the upper and lower faces and,

because of the shape, has significantly pronounced sharp

edges, particularly where the land joins the tablet sidewall.

For a tablet shaped like this, there are two areas prone

to erosion during film coating. One is at the center of the

tablets upper and lower faces, where tablets tend to be

softer and thus more friable. The other is at the tablet

edges, which are likely to chip away during tumbling.

Altering the tablet shape (lower diagram) can mini-mize both of these problems. Note how this tablet was

made using dual-radius (compound radius) punches,

where the center of the tablet is much flatter than the

tablet above it. The surface also becomes more curved

toward the tablet edges. This kind of geometry simulta-

neously minimizes erosion at the central core and the risk

of erosion or chipping at the edges.

Tablet shape may also help minimize other problems,

such as twinning. Consider the classic capsule-shaped

tablet with its parallel flat sidewalls. If the flat surfaces of

two of these tablets come into contact during the high-

tack phase of film coating, they will likely stick together,with the dry film coating acting as an adhesive. To avoid

that problem, the tablet could be made with a slight

degree of curvature at the edges, which would minimize

the area of contact and thus reduce the likelihood that

tablets would bond.

Figure 5 shows how tablet curvature leads to erosion.

Here tablet erosion has occurred in the center of the

upper or lower face, a problem possibly compounded by

the presence of a logo, which may have weakened the

tablet surface. During the coating process, erosion

observed around the logo is not only unattractive, but

reduces the legibility of the logo to a point where it no

longer aids product identification. In cases where a cen-

tral logo increases the risk of surface erosion, consider

changing the logo design or placing it elsewhere on the

tablet. For instance, placing the logo around the edges of

the tablet (Figure 6) may eliminate this kind of erosion.

Formulating film coatings

When formulating film coatings, there are several

requirements to keep in mind. One is to make sure that

the coating has the appropriate mechanical properties,

which typically involves optimizing:

Tensile strength

Elastic modulus (an indicator of coating flexibility)

Adhesion of the film coating to the tablet surface.Internal stresses are also of interest. These are the

forces that build up in any polymer film produced from

solution as the liquid portion evaporates, decreasing coat-

ing volume and causing the film to contract. While there

is nothing to be done to eliminate these stresses within

the structure of the coating, there are formulation tech-

niques that can minimize their impact.

Another important area is managing the viscosity of

the coating solution or suspension to optimize the

sprayable solids. For example, in a coating process with

inadequate drying, spraying a more concentrated coating

liquid could help since there would be less solvent(water) to evaporate.

The two case studies that follow illustrate how the film

coating formulation was used to resolve two coating

problems: edge chipping and logo bridging.

Edge chipping. There are many possible root causes

of edge chipping, but the two most common causes are a

tablet core that lacks robustness and a coating process

that is too aggressive. The top photo in Figure 7 shows a

chipped tablet, with the tablet core clearly visible where

the coating was chipped away. In this case, neither the

tablet core nor the coating process was to blame. Rather,

the problem stemmed from the inadequacy of the coating

formulation itself.

The critical characteristics of a film coat include film

strength, elongation (a measure of the flexibility), tough-

ness, and adhesion to the substrate. To resolve the chip-

ping problem in this case, two general approaches could

be used: 1) improve film strength (at the risk of reducing

flexibility) and 2) increase film flexibility to obtain proper

film formation (at the risk of reducing film strength).

In this case, the decision was to improve film strength as

much as possible without jeopardizing the films other key

properties. As can be seen in the lower photo in Figure 7,

Figure 5

Surface erosion associated with poor logo design andplacement

Figure 6

In place of conventional logo placement (left), placinglogo around the edges of the tablet (right) may helpeliminate erosion of tablets made with soft crowns.

LEGEND

LEG

END

L

EGEND


6/7

this approach succeeded. The coated tablets showed no

evidence of edge chipping. An examination of the proper-

ties of the revamped formulation revealed a significant

increase in film strength. While a little film flexibility and

adhesion were sacrificed, the compromise had no negative

consequences. Film toughness remained about the same.

However, if film adhesion had declined much more,

we may have seen film bridging (logo bridging) develop.

In fact, some give-and-take is inevitable, but when look-ing to resolve a problem in the coating formulationfilm

strength, for exampleit is critical not to compromise

other formulation attributes to the point that a new prob-

lem replaces the previous one.

Logo bridging. The next case involves logo bridging

(upper photo of Figure 8). Notice how bridging has

obscured the logo to the point where only the S in ISP

is visible. The physical characteristics of this particular

coating formulation are mixed: While the film is mechan-

ically strong, it has little flexibility and low film adhesion.

In order to resolve this bridging problem, a formulator

may wish to improve both flexibility and, more impor-tantly, film adhesion. In so doing, the logo has become

clearly visible (lower photo of Figure 8). The changes

also greatly improved elongation (thus flexibility) and

film adhesion.

The success of the approaches in these examples is due

in large part to a database developed using a statistical

design-of-experiments approach. The database gave the

formulators confidence in the consequences of their pro-

posed changes.

Tabletting process issues

In terms of proactive troubleshooting, it is also impor-

tant to consider the process that precedes the film coat-

ing process: tabletting. The objective of every tabletting

department is to manufacture tablets of suitable quality

and robustness on a production scale. But sometimes

these good tablets are less than ideal for film coating.

For example, content uniformitythat every tablet has

the correct amount of activeis an important considera-

tion in tablet making. However, there are other ingredients

in the formulation that, if not distributed uniformly, may

hinder the creation of a good film-coated product. Ina-

dequate distribution of superdisintegrants, for example,

might cause large disintegrant particles to appear at or near

the tablet surface, where they are easily wetted during coat-

ing. Such wetting can cause the particles to swell and allowthem to dislodge, leaving small pits on the tablet surface.

Another issue is robustness. When manufacturing

tablets, the goal is to impart certain measureable attrib-

utes, such as breaking force and friability, to the tablets.

To that end, sometimes in-process adjustments are made,

such as increasing compaction force. While that may

solve a tabletting problem, the adjustment may also

reduce porosity, which in turn may decrease adhesion.

(See Figure 9.) This is an important consideration, since

the greater the degree of porosity in the core, the better

the adhesion of the coating. Why? Because when a film

coating is applied, the solution penetrates the tablet sur-

Figure 7

Eliminating edge chipping

Property ValueFilm strength (g mm-2) 1,924

Elongation (%) 17.2

Toughness (g mm-2 %) 25.13

Film adhesion (g mm-2) 346

Property Value

Film strength (g mm-2) 3,619

Elongation (%) 11.8



a. The problem

b. The solution

Figure 8

Eliminating logo bridging

Property Value


Elongation (%) 4



Property Value


Elongation (%) 15



a. The problem

b. The solution

Figure 9

Influence of tablet core porosity on ultimate film adhesion

0 5 10 15 20 2520

30

40

50

60

Tablet porosity (%)

Filma

dhesion(kPa)

Pharmacoat 606

Methocel E50

a. Hypromellose 2910, Shin-Etsu Chemical. www.biddlesawyer.comb. Hypromellose 2910, Dow Chemical. www.dowexcipients.com


7/7

face to some degree. That helps lock the film coating

onto the surface and enhances adhesion. The lower the

porosity of the tablet, the shallower the penetration into

the surface, and adhesion suffers.

Conclusion

The tablet core formulation, the tablet core design,

the film coating formulation, and the tabletting process

are important areas to consider when troubleshootingpotential film coating problems. The design of the coat-

ing process and coating equipment maintenance are also

important. But whichever variable you investigate, be

aware that problems that occur during film coating often

have more than one root cause. That means the resolu-

tion is rarely limited to a minor process change. Indeed,

the simplest, most effective approach to problem solving

is to avoid the problem completely by troubleshooting

proactively. T&C

Stuart C. Porter, Ph.D., is senior science fellow of film coatingtechnology at International Specialty Products, 1361 Alps

Road, Wayne, NJ 07470. Tel. 973 628 4000, fax 973 628

4001. Website: www.ispcorp.com. Porter is also a member of

Tablet & Capsules Editorial Advisory Board.

problemas en tabletas recubiertas

Documents