Micromilling and co-micromilling of small quantities of poorly water-soluble pharmaceutical API - Bertin Instruments

Pharmacology

Micromilling and co-micromilling of small quantities of poorly water-soluble pharmaceutical API

Sources: Bertin Pharma, France [1]

Context

Micromilling and co-micromilling of drugs with specific pharmaceutical excipients is an interesting approach for increasing the solubility and the dissolution rate of poorly water-soluble compounds. In preclinical development and early clinical formulation development, the amount of active pharmaceutical ingredient (API) available is often limited and specific process requiring micro quantities (100-200 mg) of drug for formulation screening is of high need. Evaluation of co-micromilling with various pharmaceutical excipients with regards to this limitation is in fact difficult to perform with classical milling equipment. In this respect the performance of Precellys®24 has been studied [1].

 

[1] Precellys24 as a useful screening tool in preformulation for micronisation and co-micronisation of smallquantities of poorly water-soluble pharmaceutical API, A. Colin et al. 2nd Conference on Innovation indrug delivery, 3-6 October, 2010, Aix-en Provence

Results

A significant increase of the Ketoprofen dissolution rate is observed after co-micromilling using various excipients, compared to non micromilled material. This increase is observed for excipients which have or do not have solubilizing properties (surfactant vs PVP derivatives) (Figure 1). Significant particle size reduction is observed for comicromilled formulations such as Crospovidone-Ketoprofen (Figure 2). Drug dissolution following comicronisation has been significantly improved. No amorphisation of the API was found after the process [1].

 

Percentage of Ketoprofen released versus time (min). Co-micromilled material (orange), physical mixture (green) and ketoprofen non microzed (blue) (mean ± SEM, n=3).

Percentage of Ketoprofen released versus time (min). Co-micromilled material (orange), physical mixture (green) and ketoprofen non microzed (blue) (mean ± SEM, n=3).

 

Scanning electronic microscopy of non-micromilled ketoprofen and co-microlilling formulation (scale:50µm).

Scanning electronic microscopy of non-micromilled ketoprofen and co-microlilling formulation (scale:50µm).

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