Multivariate analysis in the development of bioequivalent tablets containing bicalutamide

Abstract

The pharmaceutical industry has to tackle the explosion of high amounts of poorly soluble APIs. This phenomenon leads to numerous sophisticated solutions. These include the use of multifactorial data analysis identifying correlations between the components and dosage form properties, laboratory and production process parameters with respect to the API liberation Example of such API is bicalutamide. Improved liberation is achieved by particle size reduction. Laboratory batches, with different PSD of API, were filled into gelatinous capsules and consequently granulated for tablet compression. Comparative dissolution profiles with Casodex 150 mg (Astra Zeneca) were performed. The component analysis was used for the statistical evaluation of f₁ and f₂ factors and D(v,0.9) and D[4,3] parameters of PSD to identify optimal PSD values. Suitable PSD limits for API were statistically confirmed in laboratory and in commercial scale with respect to optimized tablet properties. The tablets were bioequivalent with originator (n = 20; 90% CI for ln AUC_0–120: 99.8–111.9%; 90% CI for ln c_max: 101.1–112.9%). In conclusion, the micronisation of the API is still an efficient and inexpensive method improving the bioavailability, although there are more complicated and expensive methods available. Statistical multifactorial methods improved the safety and reproducibility of production.

Keywords:

• Bicalutamide
• dissolution
• particle size
• bioequivalence
• multivariate statistics

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The research was funded by Pliva, d.o.o., and its daughter company Pliva Lachema, a.s.