Drug Tablet Design – Why Pills Come in So Many Shapes and Sizes

pile of colorful drug tablets pills

Have you ever wondered why drug tablets come in so many shapes, sizes, and even colors? Or why we sometimes have to take two pills instead of one? One of the last steps in drug design and development is to pack it all into a nice little tablet. It might sound simple, but lots of factors go into deciding the final form of medicines. How do pharmaceutical companies design the picture-perfect pill?

The Colorful World of Pills

The drug market is dominated by medicines in the form of tablets, handy little pills we can take at our convenience. These tablets contain the active pharmaceutical ingredient (API), the ‘good stuff’ that makes us feel better through chemical interactions in our bodies.

A tablet also contains excipients – inert compounds that can also serve as drug delivery systems. Excipients can control the rate at which the API is released into the bloodstream, where it can exert its therapeutic effects. Once the API and excipients are perfected in a medicinal chemistry program, the next step in drug development is the design of a suitable tablet to package it in.

Pharmaceutical companies can choose to be boring and simply stick to standard round white tablets; in fact, this is what is usually given to patients during clinical trials. After all, it wouldn’t make sense to spend the time and effort on tablet design if the drug never makes it to the market!

However, tablet design is an important part of drug development, evident in the structural diversity of the medicines we take. As patients, we often form associations between a drug’s form and its function. From the iconic blue diamond of Viagra (sildenafil) to the chunky white ovals of Lipitor (atorvastatin), how do pharmaceutical companies decide on the best design for their pills?



Drug Tablet Design

Size

The size of drug tablets can range from tiny spheres packed in capsules to large, bulky rods. When it comes to tablet design, smaller is usually better, but factors like the target patient demographic have to be taken into account. Some individuals, especially children, have difficulty swallowing larger pills, which might deter them from taking the medication altogether. However, tiny pills are harder to handle, especially in the older population who might have poorer dexterity and eyesight.

In addition, how small a pill can get is dependent on the dosage. If a single dose of a drug requires a large amount of API or excipients, they are sometimes split into two smaller pills. In most cases, patients prefer a single tablet per dose, as they might forget (in the case of older patients) or refuse to take multiple tablets (in the pediatric population).

Shape

While the size of a drug may be dependent on the dose, a tablet’s shape provides a little more freedom for modification. However, the surface area to volume ratio must be considered, as this can affect the rate of API release from the drug delivery components. It is possible to simulate drug release kinetics using mathematical models, ensuring that the shape doesn’t affect the dissolution of the drug1.

Most tablets end up circular or with rounded corners, simply because they make the tablets easier to swallow. If the size of the dose is large, choosing the right shape can give the perception of a smaller tablet. Larger elongated shapes such as an oval or rectangle tablet are much easier to swallow than a large triangular pill!

drug tablet design shapes and profiles
Common tablet shapes and profiles that can be found on the drug market (Source)

It can be worthwhile to throw in a little bit of creativity when it comes to shapes. For example, a heart-shaped pill for a cardiovascular drug is a unique way of differentiating it from others. In many cases, having a unique tablet shape can also establish recognizability and brand loyalty in the medication.



Color

Being organic compounds, the components of drugs usually mean pills are naturally white. However, the range of dye pigments available provides us with the entire spectrum of color to design drugs with. The light blue color of Viagra gives individuals a feeling of happiness and relaxation, being associated with the color of the sky and the ocean. Many heart medications are colored red or pink, signifying both power and danger2.

You don’t see many black tablets as the color is often associated with death and other negative emotions. Other colors such a greenish-yellow is also seldom seen as it reminds individuals of vomit, evoking feelings of sickness and disgust. The color of a tablet can influence patient compliance, as they are more likely to take their medication consistently if they find it to be visually appealing.

It’s not all invoking the right emotions in the patient, however, with certain regulations requiring differentiation between dosage forms of the same drug. Pharmaceutical companies aren’t allowed to color all its tablets the same color, as convenient as that sounds. This is a failsafe measure, preventing pharmacists and doctors from dispensing the wrong drug while protecting patients from potential medicine mix-ups.

valium dosage forms roche different sizes
The popular tranquilizer diazepam, better known by its brand name Valium, is marketed by Roche in three dosage forms. Although the dimensions are the same for each tablet, they differ in color.

Depending on the country it will be marketed in, there may be further regulatory guidelines regarding the use of certain pigments or additives in drugs. For example, certain red dye pigments (Red 21, 27) are prohibited in Japan, although they are allowed in U.S. and EU markets. All forms of a certain yellow dye (Yellow 10) is allowed in Japan, whereas the EU only allows its disodium salt, while the U.S. Food and Drug Administration does not certify the disodium salt.

Additional Markings

Many drugmakers also choose to etch certain words, numbers, or even symbols on the surface of their tablet. Sometimes, tablets are scored along the middle to allow for easier breaking into smaller doses. In addition to providing the patient with a further form of identification, these markings also make it more difficult for counterfeit versions of the drug to be manufactured.

The counterfeit drug industry is worth billions, with illegal drug manufacturers selling their products online and through channels that bypass regulation. Having additional features, such as a special film coating or a unique flavor, helps officials and consumers to differentiate between the genuine and counterfeit versions of a drug3.

counterfeit authentic pills identification
Screening technology developed by the U.S. FDA allows for quick identification between authentic and counterfeit drugs, taking advantage of differences in the fluorescent properties of tablets and film coatings.

Wrapping it Up

The extent of tablet design has to be balanced with the costs involved. For each additional feature on the tablet, the cost of producing the drug goes up. Furthermore, specialized manufacturing equipment may be required for pills with special shapes and designs. Pharmaceutical companies spend upward of US$2 billion on drug development for each approved drug, so it is important to be cost-efficient in both research and manufacture.

Reducing costs, fulfilling regulatory requirements and being patient-friendly while deterring counterfeit is no easy feat. In addressing all these factors, drug tablet design becomes a task that demands careful consideration and planning paired with a degree of flair and creativity.



Reference

  1. Paolino, D., Tudose, A., Celia, C., Di Marzio, L., Cilurzo, F., & Mircioiu, C. (2019). Mathematical Models as Tools to Predict the Release Kinetic of Fluorescein from Lyotropic Colloidal Liquid Crystals. Materials12(5), 693.
  2. NAz, K. A. Y. A., & Epps, H. (2004). Relationship between color and emotion: A study of college students. College Student J38(3), 396.
  3. Platek, S. F., Ranieri, N., & Batson, J. (2016). Applications of the FDA’s Counterfeit Detection Device (CD3+) to the Examination of Suspect Counterfeit Pharmaceutical Tablets and Packaging. Microscopy and Microanalysis22(S3), 1072-1073.

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