From lab to upscale – Boosting formulation performance through in vitro technologies

The determination of the in vitro release profile is a useful tool during product development, since it can provide essential data on semisolid product microstructure. The present work aimed at providing the assumptions to assist a sustainable improvement of an anti-inflammatory semisolid dosage form pharmaceutical performance. The qualitative/quantitative composition and the production process were already well-established, however, there were some parameters that lacked optimization, namely: (i) sodium hydroxide content (ii) carbopol viscosity and finally (iii) mixing time. Since these parameters induced fluctuations in the microstructure profile, they were identified as critical. Efforts were then made to rationalize, predict and ultimately maximize the effects of these parameters on the product pharmaceutical performance. For that, a 2³ full factorial design was employed to assess the impact of the above mentioned parameters, on the pharmaceutical performance. During this optimization phase, all manufactured batches were produced at a laboratory scale.

Our results enabled the identification of three main formulation groups: high (659.53-723.67 µg/cm²/√h), moderate (598.99-651.14 µg/cm²/√h) and low release rate formulations (499.30-507.59 µg/cm²/√h). These results were noteworthy correlated with sodium hydroxide content (higher sodium hydroxide inducing higher release), and on a smaller degree to the carbopol viscosity (higher viscosity yielding superior drug release).

To confirm these assumptions, the obtained outcomes were translated from lab to industrial scale, with the sole aim to validate the working conditions in line with the predefined quality target product profile (QTPP). As widely known, semisolid microstructure is highly dependent on batch production size. The same trends were observed, even though IVRR suffered a slight decrease when compared to the lab scale batches. Nevertheless, quality target and response constraints monitoring during DoE laboratory studies, enabled a successful implementation of the optimal production conditions at an industrial scale. By doing so, a product with superior pharmaceutical performance was attained.