HPMC granules by wet granulation process: Effect of vitamin load

Abstract

Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various fields such as pharmaceuticals, biomaterials, agriculture, food, water purification. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45–2 mm in size, was fully characterized. Results showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45–2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.

 

Conclusions

In this work, the effect of different loads of vitamin B12 on the main technological properties (yield process, compressibility index, mechanical and release properties) of HPMC granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were studied and two loading methods (B12 in binder phase and B12 in mixed polymer powder) were tested.

Results showed that the B12 loading by binder phase dispersion allowed a homogeneous particles- bulk including the vitamin. Incorporation of 5% of B12 in the HPMC powder has produced a lower granulated mass (process yield: 61 %) and a higher big scarp (40 %), compared to the unloaded granules (process yield: 75%; big scrap: 21 %) and those loaded with 1% (process yield: 71 %; big scrap: 29 %) and 2.3% (process yield: 79 %; big scrap: 21 %), within the marketing useful range size of 0.45-2 mm. Moreover, at 5% in B12 granules present higher porosity, and are more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. The DSC analyses have detected a thermal stability of the loaded granules and an amorphous dispersion of vitamin B12 in the HPMC matrices.

Vitamin release properties of fresh-prepared and aged granules, were roughly found the same for the three kinds loaded lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better physical incorporation. It is important to note that already at 1%, a small amount of loaded granules, 0.1 g, contains the recommended dose of vitamin B12 for oral administration by food supplementations (in the first week of oral therapy 1000 μg daily are required). At last the achieved results emphasize that hydroxypropyl methylcellulose, a carbohydrate based polymer able to form hydrogel structures, is suitable in granular structures to entrap and protect vitamin B12 for functional molecule release purposes.

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