(W1230-08-54) Overcoming Flow, Blend Uniformity and Direct Compression Tabletability Challenges in Micronized APIs Through Use of Multi-Functional Excipients

Purpose: Powder segregation is a common risk when processing directly compressible formulations particularly for a difficult to process API like micronized Mefloquine HCl. This API has needle shaped morphology, d90 < 10 µm, bulk density < 0.2 g/cm³ and shows poor flow. In most cases, a more complex wet granulation method is required to overcome all these problems. However, the aim of this study was to use multifunctional excipient-based blend and compare its blend uniformity, flowability and tabletability profile with individual excipient-based blend to prepare tablets by direct compression.

Methods: Two different types of blends were prepared. 1) API was mixed using a multifunctional co-processed excipient like Kollitab^TM DC 87 L (MFE-B)  and 2) API mixed with individual excipients (IE-B) having composition similar to that of Kollitab^TM DC 87 L. Blends were prepared at 5 and  10% drug loading. Flow function coefficient was tested using FT4. Blending was done for 30 and 45 min using turbula mixer.  Blend samples were collected from different locations of the blender and analyzed for blend uniformity assay (n=5) by HPLC. The final blend was compressed on a compaction simulator (Korsch Styl One Nano) at five different compression pressures ranging from 75 to 250 MPa using round, flat 11.28 mm diameter punch. Tabletability and disintegration profiles were generated to compare the feasibility of making tablets using these blends.

Results: The powder flow of the MFE blend was classified as good, whereas the IE-B blend exhibited fair powder flow characteristics. Acceptance criteria for BU assay set was 90 to 110% with no individual samples falling out of this range for this feasibility testing. With IE- blend the blend uniformity assay failed at 5% and 10% DL at both 30 and 45 min.  However, MFE-blend showed assay within 90 – 110% range for all the individual samples tested at both 5% and 10% DL at 30 and 45 min.  IE- blends showed around 2 to 4 fold higher variability in assay compared to MFE- blends. Tabletability of MFE- blend was significantly superior compared to IE- blend tablets which produced softer tablets. IE- blends were poorly compressible and did not achieve 1.5mPa tensile strength even at 250 MPa compression pressure.

Conclusion: Multifunctional excipient like Kollitab^TM DC 87 L proved to be effective in preparing simple directly compressible formulations of a highly cohesive micronized API at 5, 10% DL without any segregation at lab scale.

Table 1: Blend uniformity assay of MFE- blend and IE- blend at 5 and 10% DL

Figure 1: Tabletability profile – Compression pressure Vs Tensile strength of MFE-Blend & IE-Blend at 5 and 10% Drug Loading

Figure 2: Disintegration profile -Tensile strength Vs Disintegration of MFE-Blend & IE-Blend based tablets at 5 and 10% Drug Loading