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Divyakant Desai

Divyakant Desai, Ph.D., is a Research Fellow in the Bristol-Myers Squibb Company.

 
Generally, tablets are coated to mask the taste, enhance the appearance, improve swallowability, and/or to protect from photolytic degradation. During the 1970s and 1980s, some of the over-the-counter tablet products were enteric coated to offer a modified release profile. They were further sugar coated with a second dose of the drug for the immediate release. However, their performance was highly dependent on gastric transit time and gastric pH variability. This was before the advent of Quality-by-Design (QbD). Therefore, tablet content uniformity, polymorphic form issue for the drug substance, and other critical product attributes were not adequately addressed. Lately, an active coating has resurfaced as one of the major emerging trends in the coating technology.

For the majority of tablet formulations, drugs are mainly in the tablet cores. The manufacture of tablet cores involve many unit operations such as mixing of drug with excipients, dry or wet granulation, milling of granulates, or mixing of milled granules with a lubricant followed by tablet compression. All these unit operations involving manufacture of the tablet cores need to be tightly controlled and monitored to produce quality products. If the tablets’ cores need to be coated eventually for the reasons mentioned above, wouldn’t it make sense to add the drug in the coating solution itself and to spray on the inert tablets cores? With such an approach, only one unit operation involves drug substance and therefore critical for the quality of the product.

An active coating approach also offers great flexibility to formulate drug products following the QbD paradigm. Using an active coating approach, two incompatible drugs can be separated by incorporating them into two separate coating layers, or one drug in the tablet core and the other in the coating layer. An active coating approach can also make it feasible to have two separate drug release profiles. For example, a controlled release core can be coated with an immediate release active coat. Thus, an active coating approach can be very useful to formulate fixed dose combination products.

If an active coating approach is so useful and simple, why are only few commercial tablets manufactured using this approach?

Although the active coating involves only on-unit operation with the drug substance, it is a very challenging operation. There are four main challenges. First, how to determine the coating end point so when the coating is stopped, the tablets contain target amount of the drug. Second, how to control tablet to tablet coating variability. If that is not tightly controlled, the coating variability can lead to drug content variability. The third challenge is coating process efficiency. The process efficiency is defined as the amount of coating deposited to the amount of coating applied. For the commercially viable process, the coating efficiency should be 95% and above. The fourth and final challenge is the polymorphic form of the drug substance once coating is deposited. If the polymorphic form is different than the starting form, it can lead to variability in drug product stability and dissolution. The fourth challenge is drug specific so no general remedy can be suggested. However, the first three challenges are general technology related challenges and have been addressed. The coating end point determination challenge has been addressed by Desai et al.; coating uniformity challenge is addressed by Chen et al.; and coating efficiency challenge has been addressed by Wang et al.

Advances in process analytical technology and the published coating model, which has been validated from pilot to commercial scales, should make active coating less challenging for the formulator, and they should utilize it as warranted by the situation.