Qualification of a mixer: how to obtain the homogeneity of a mixture of powders?
Hôpital Clocheville, CHRU Tours, France
In order to limit the development of the musculoskeletal disorders that pharmaceutical assistants (PA) develop, the pharmacy obtained funding for a mixer for the mixture of powders for capsules. The goal is to qualify the mixer by obtaining homogeneous mixtures.
For each preparation, different mixing times and speeds were tested, determined by an empirical method based on the literature and supplemented by exchanges with Hospitals using this mixer. For the production of the capsules, the tests focused on the active principle (AP) whose content was measured in the control laboratory (CL), starting with the AP whose content was regularly non-compliant (NC): melatonin 1 and 3mg, propranolol 1, 2, 5, 10mg, hydrocortisone 1 and 2mg, dexamethasone 2 and 5mg, carvedilol 1mg, amiodarone 10mg, spironolactone 10mg. The chosen excipient is micronized lactose (ML). After mixing the powders and putting in a capsule, 10 units are sent to the CL: an assay by UV-visible spectrophotometry is carried out to determine the AP content relative to the mass of powder contained in each of the capsules. The coefficient of variation (CV) of the content between the 10 capsules was then calculated: the homogeneity is proven for a CV≤5%.
For the AP / ML mixtures tested, homogeneity is obtained from 8 minutes (min) at 500 rpm (rpm) except for 1 mg propranolol. The influence of the stirring time on the homogeneity of a mixture would be preponderant comparing to the speed according to the literature: indeed, a CV> 5% is found for the tests of mixtures at 5min 500 rpm. Tests are underway to find the optimal parameters for propranolol 1mg / micronized lactose. The results obtained for the powder mixtures could have been influenced by the experimental conditions: the preparation environment (humidity and temperature), the transport to the CL and the change of operators between the tests within the preparatory and the CL.
Most of powder mixtures are in accordance with the content according to the European Pharmacopoeia with demonstrated homogeneity after 8 min at 500 rpm. The influence of the mixing speed on the homogeneity is under evaluation. The PA are very satisfied with the mixer: time saving, smoother production and less repetitive movements. In addition, our establishment is a large consumer of capsules, a galenic form not always suitable for pediatrics. The results of the stability study of an oral suspension (OS) of spironolactone potentially harmful excipient with an undesirable effect were very conclusive; tests will be carried out with the mixer on the development of OS from the AP tested previously.