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Blend uniformity represented by the RSD (n = 20) for three-component powder blends of lactose (anhydrous or monohydrate), MCC and paracetamol (2% or 30% w/w). Blends are prepared by 1 min batch mixing, 30 min batch mixing and continuous mixing. The sample marked with * corresponds to an RSD of 68%.

Blend uniformity represented by the RSD (n = 20) for three-component powder blends of lactose (anhydrous or monohydrate), MCC and paracetamol (2% or 30% w/w). Blends are prepared by 1 min batch mixing, 30 min batch mixing and continuous mixing. The sample marked with * corresponds to an RSD of 68%.

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The material properties of excipients and active pharmaceutical ingredients (API's) are important parameters that affect blend uniformity of pharmaceutical powder formulations. With the current shift from batch to continuous manufacturing in the pharmaceutical industry, blending of excipients and API is converted to a continuous process. The relati...

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... an average particle size of 32 μm is used as API. Blends are prepared both at a low API dosage of 2% w/w and a high API dosage of 30% w/w. The lactose-MCC ratio is varied from 25% to 75% MCC of the total amount of excipient. As a comparison, also binary API-excipient blends with only lactose or MCC as the excipient are included in this section. Fig. 6 shows how blend uniformity of three-component mixtures depends on its composition and the blending method. For the batch process, two different blending times of 1 min and 30 min were used. For the continuous process only one time point was evaluated, since no timedependence was observed for the continuous blending of binary mixtures. ...
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... in feed rate will likely have little effect on blend uniformity. For batch blending of anhydrous lactose with MCC and API, very high RSD's are observed indicating poor blend homogeneity. Especially batch blends with low API dosage show poor uniformity, with an RSD of 68% for a 1:1 ratio of lactose and MCC and a blending time of one minute (Fig. 6a). Also at a higher API dosage of 30%, ternary blends of anhydrous lactose and MCC show higher RSD's than the binary blends (Fig. 6b). For the continuous process on the other hand, the ternary blends show very good homogeneity. The observed RSD's are even slightly lower than for the binary blends, both at low and high API dosage (Fig. ...
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... high RSD's are observed indicating poor blend homogeneity. Especially batch blends with low API dosage show poor uniformity, with an RSD of 68% for a 1:1 ratio of lactose and MCC and a blending time of one minute (Fig. 6a). Also at a higher API dosage of 30%, ternary blends of anhydrous lactose and MCC show higher RSD's than the binary blends (Fig. 6b). For the continuous process on the other hand, the ternary blends show very good homogeneity. The observed RSD's are even slightly lower than for the binary blends, both at low and high API dosage (Fig. 6a,b). A likely explanation for the poor uniformity of the batch blends is the large difference in material properties for anhydrous ...
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... minute (Fig. 6a). Also at a higher API dosage of 30%, ternary blends of anhydrous lactose and MCC show higher RSD's than the binary blends (Fig. 6b). For the continuous process on the other hand, the ternary blends show very good homogeneity. The observed RSD's are even slightly lower than for the binary blends, both at low and high API dosage (Fig. 6a,b). A likely explanation for the poor uniformity of the batch blends is the large difference in material properties for anhydrous lactose and MCC. The bulk density of anhydrous lactose is more than two times higher than for MCC and the average particle size is three times higher. Previous research has shown that powders with large Fig. 5. ...
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... are obtained ( Oka et al., 2017). So the mismatch in material properties between anhydrous lactose and MCC results in poor homogeneity in a batch process, whereas for a continuous process this is no issue. Ternary blends of milled lactose monohydrate, MCC and paracetamol show a similar difference between a batch and continuous blending process (Fig. 6c,d). For the batch process, relatively high RSD's are observed for ternary blends compared to binary blends. Homogeneity of blends with lactose monohydrate, however, is better than for blends with anhydrous lactose because of a smaller difference in particle size and bulk density between the two excipients. For the continuous process ...

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Article
The properties of pharmaceutical powders, and the liquid binder, directly influence the penetration behavior in the wet granulation process of the pharmaceutical industry. Conventional methods encounter challenges in understanding this fast process. In this work, an emerging synchrotron-based X-ray imaging technique (having fast imaging capability) was employed to investigate the internal process from 2D and 3D to real-time (in-situ with ms time intervals) 3D (also considered 4D) perspectives. Two commonly used excipients (lactose monohydrate (LMH) and microcrystalline cellulose (MCC)) were used to make binary mixtures with acetaminophen (APAP) as the active pharmaceutical ingredient (API). Isopropanol and water were employed as liquid binders in the single droplet impact method. Results showed that for most of the mixtures, the porosity increased at higher fractions of APAP. MCC mixtures experienced less agglomeration and more uniform pore distribution than LMH ones, resulting in a faster droplet penetration with isopropanol. Moreover, the imbibition-spreading studies showed that isopropanol penetration in MCC powders followed more unidirectional vertical movement than horizontal spreading. Our results also demonstrated that simultaneous granulation of LMH with water resulted in much slower penetration. This study revealed that synchrotron X-ray imaging can investigate 3D internal pore structures and how they affect the quantitively real-time internal penetration dynamics.