Vacuum-sealed packaging of an active pharmaceutical substance
Publication Date: 2010-May-31
The IP.com Prior Art Database
The present publication relates to a vacuum-sealed packaging of an active pharmaceutical substance which enhances its stability.
Olanzapine, chemically named 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3b][1,5]benzodiazepine, is an active pharmaceutical compound useful in medical treatments as antipsychotic agent, particularly for the treatment of both the positive and negative symptoms of schizophrenia. Olanzapine is marketed worldwide as free base under the brand name Zyprexa® by E. Lilly.
Olanzapine, as final result of a chemical process of synthesis, can contain impurities derived from many sources (the starting materials or the chemical modifications involved during the synthesis, for example). Additionally, it is known from the art that impurities in a pharmaceutical ingredient may arise from the degradation of the same. Impurities generated upon degradation of an active substance can reduce the therapeutic effects of the same and unnecessarily burden the body with degradation products. Consequently, this is related to the stability of the compound during its storage.
It is well known1,2,3 that olanzapine degrades under oxidizing conditions, being very important the system of packaging of the compound in order to keep the purity of the same.
The object of the present study was provided a system of packaging of olanzapine, more concretely the crystalline form I of the active compound, so as to enhance its stability. The stability of olanzapine can be improved by packaging it into a bag, applying vacuum and further to heat seal the bag. With this method can be guaranteed the absence of oxygen and avoid the degradation of the compound.
The packaging material for the package system can be chosen from a blend or laminated structure combination of different compounds as polyethylene or polyethylene terpthalate, polypropylene, polyamide, aluminium and polyester. Within our study, we obtained the best results with a bag constituted by the combination of three laminated materials: Polyester 12-15 micron, Aluminium 9-12 micron and linear polyethylene 60-100 micron. The aluminium bags have a grammage of 130-145 g/m2 and a thickness of 80-125 micron. In this manner, the packaging components allow to work with vacuum and it is possible to avoid oxidation/degradation and protect from light and moisture the samples of the active compound.
The vacuum sealed packaging can be combined with a moisture absorber (silicas, zeolites, diatomaceous earth, activated carbon...) if it is necessary. Moreover, it is possible to place the active substance into the bag with a nitrogen atmosphere in order to eliminate the oxygen and further apply vacuum and heat seal the bag. In our case, the olanzapine compound of the study exhibits crystalline form I, but it has not to be restricted to this concrete polymorph.
Olanzapine substance was obtained by means of a general process described in US patent with number 5,229,382. The reaction between 4-a...