TopMill Pigment Premix Reduces Spotting in Colored Tablet Cores

TopMill, a milled ready-to-use pigment and dye premix, produced tablet cores with no by-eye detectable defects in direct compression trials, according to a case study from BIOGRUND.

Uncoated, colored tablet cores can distinguish dosage strengths, but a simple pigment blend can leave the surface spotted. BIOGRUND compared a conventional iron oxide pigment blend against TopMill, its milled ready-to-use pigment and dye premix, both at 5 percent in a tableting mixture after direct compression. Under microscope evaluation the case study reports an average of 8 spots per tablet for the pigment blend and 0.8 for TopMill, plus a customer case where spotted cores became homogeneous with a milled premix.

The challenge

• Three strengths, three colors: A pharmaceutical customer developed 5 mg, 10 mg, and 15 mg dosages of one active pharmaceutical ingredient (API), to be distinguished by uncoated tablet cores colored orange, pink, and red respectively.
• A fixed core formulation: The core formulation was already set.
• Spotted surface: The cores came out with a spotted tablet surface and an appearance judged unacceptable, against a target of a homogeneously colored core.

The approach

• BIOGRUND reviewed the formulation ingredients.
• Colors were matched.
• An adjustment was recommended that left the quantitative formulation unchanged.
• Direct compression trials were run.

The solution

TopMill is a ready-to-use coloring system for all kinds of dosage forms, supplied as a dry milled powder of pigments or dyes combined with additional excipients, for example iron oxides with microcrystalline cellulose (MCC). Red, yellow, and black iron oxide are milled on a Bohle Turbo Miller hammer mill, then sieved or ground, with up to three MCC dilution steps available on demand. For this customer, BIOGRUND recommended a milled pigment premix for direct compression to give a better particle size distribution and a homogeneous pigment distribution, then blending that premix into the tablet mass before compression.

[FIGURE: particle size distribution of iron oxide red (Fe2O3) before and after milling, PDF page 11]

Results

The comparison ran a conventional iron oxide pigment blend and TopMill each at 5 percent in a tableting mixture. With the pigment blend, one fifth of the tablet cores showed spots visible by eye (n=25), and microscope evaluation found spots in every tablet. With TopMill, the document reports no by-eye detectable defects and spots in 30 percent of the tablets under the microscope. Both evaluations used a Leica S9i microscope at 10x. In the customer case, direct compression without the pigment premix gave a heterogeneous colored tablet core, and with the premix a homogeneous one.

[FIGURE: side-by-side comparison of tablet cores colored with the pigment blend and with TopMill, PDF page 15]

Key takeaways

• TopMill showed no by-eye detectable defects, against one fifth of cores spotted with a conventional pigment blend, per BIOGRUND.
• Under the microscope at 10x, average spots per tablet were 0.8 for TopMill and 8 for the pigment blend, each at 5 percent in a tableting mixture (n=25).
• The recommended fix was a milled pigment premix blended into the tablet mass before compression, without changing the quantitative formulation.
• TopMill is offered for tablet cores, powders, liquids, suspensions, hard candies, and panned confectionery goods.
• BIOGRUND lists shorter process times, a cleaner production process, tailor-made color development, and batch to batch consistency as TopMill advantages.

See the full case study on Introducing TopMill®: Ready-to-use pigment/dye premix here:

TopMill – Coloring iron oxide pigmented tablet core

(click the picture to download the document)

Source: BIOGRUND, case study Introducing TopMill®: Ready-to-use pigment/dye premix

Sources

1. BIOGRUND, Introducing TopMill®: Ready-to-use pigment/dye premix, case study.

This article is for informational purposes for pharmaceutical industry professionals and does not constitute regulatory advice. Always refer to the current pharmacopoeial monograph, the supplier’s current technical data sheet, and applicable regulatory guidance for your dosage form, route of administration, and market. Pharma Excipients International AG is not a manufacturer of the excipients discussed.

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