Valsartan is a highly selective inhibitor of angiotensin Ⅱ receptor subtype, which has stable anti-hypertensive effect, mild adverse reactions and good safety. It has become an internationally recognized first-line anti-hypertensive drug with great market demand.
In the current industry, wet granulation and dry granulation are mainly used in the production of valsartan oral dosage. Due to the insolubility of valsartan in water, its tendency to become sticky and hard after absorbing moisture, the wet granulation process requires the selection of appropriate excipients, which is time-consuming and high cost. In contrast, directly produce the high purity valsartan adopting the dry granulation process (without any excipients) is efficient and low cost.
Valsartan is a material that is more sensitive to temperature and pressure. In conventional dry granulation process, poor control of the pressure and temperature will reduce the production consistency of the valsartan. The worse situation is that the material may crystallize in the compression area and the front end of the feeding shell (as shown in Figure 1), resulting in equipment stuck or even damaged.
Fig. 1 Crystallization of valsartan in conventional dry granulation process
The LGX series roller compactor newly developed by Canaan, with comprehensively optimized control logic of temperature and pressure, is efficient and stable in the production of high-purity valsartan. Its advantages are as follows:
1、Newly designed intelligent temperature control system. The temperature rise of the material is less than 10℃ during the production process.
2、PID regulator with pressure control. The response speed of compression pressure adjustment is fast and the fluctuation is small.
Fig. 2 Trend Graph of Roller Pressure for LGX Series Roller Compactor
3、Unique feeding screw treatment process. The wear resistance is increased, and the cleaning difficulty is reduced.
▲ Fig. 3 Comparison of LGX part before and after cleaning
4、The intelligent production control system independently developed by Canaan can improve the compactness, consistency and granulation of products, and effectively avoids material crystallization and sticking.
As shown in Table 1, Canaan respectively carried out the continuous operation test (over 8h) on high-purity valsartan by using LGX series roller compactor and conventional roller compactor, and took samples for testing. The results showed that the key data of samples at different stages had little difference, and the isomer content was less than 0.7% (in line with the requirements of European Standard), while the production with conventional roller compactor had different degrees of cleanliness, and the isomer content was close to 1.5%.
Table 1 Isomer Content of Valsartan produced by dry granulation process
Isomer content in raw powder (%)
Isomer content in products by
conventional dry roller compactor (%)
Isomer content in products by LGX series roller compactor (%)
Valsartan produced using Canaan LGX series roller compactor had 0.70% isomer content in the sample taken from the surface of the feeding screw and feeding shell after granulation was completed, while the isomer content in the sample taken from the same location after production using conventional roller compactor was as high as 3.04%.
The newly developed LGX series roller compactor by Canaan is not only suitable for the production of valsartan, but also for products with complex material characteristics and high production difficulty. All pharmaceutical enterprises are welcome to provide materials for testing.