Research on Functionality of Co-processed Excipient TOMITOLTM TMT (TMT934)

1. Background

As the level of pharmaceutical preparations continues to improve at home and abroad in recent years, more and more new pharmaceutical excipients have been developed and applied. Mixing existing excipients using an appropriate process and then applying to preparations as a whole, which maintains the chemical properties of each excipient without changing its safety and makes the original excipients have new functions, has become a new hotspot in the development of the international pharmaceutical excipient industry. Such excipients are called co-processed excipients or pre-mixed excipients. IPEC-Americas and IPEC Europe jointly released the co-processed excipient guide in 2017, which has further encouraged and stimulated their development.

The booming development of new pharmaceutical excipients abroad will definitely drive the introduction and independent R&D of these products in the domestic pharmaceutical industry and facilitate the formulation of relevant regulations and industry standards. On July 26, 2020, Chinese Pharmacopoeia Commission (ChP) released the Announcement on the Draft of Guidelines for Quality Control of Pre-mixed and Co-processed Excipients on its official website (Click to view the original text).

2. Definition

From the draft of Guidelines for Quality Control of Pre-mixed and Co-processed Excipients, we can find the definitions of pre-mixed and co-processed excipients by ChP.

A pre-mixed excipient refers to a mixed excipient with certain function and homogeneous appearance prepared with two or more excipients by simple physical mixing. Each component of a pre-mixed excipient maintains its independent chemical entity. 

A co-processed excipient is a mixed excipient prepared with two or more excipients by specific physical processing (such as spray-drying and granulation) to achieve specific functions. No formation of new covalent bonds should occur during the processing of co-processed excipients. Different from pre-mixed excipients, co-processed excipients can't be prepared by simple physical mixing.

3. Co-processed Excipient TMT934

TMT934, manufactured by Topchain Pharma, is prepared by mixing microcrystalline cellulose (MCC) and mannitol in a certain ratio using a special process followed spray drying. According to definitions in Section 2, TMT934 belongs to co-processed excipients.

Table 1 Key Indicators of TMT934 

    Fig. 1 Scanning Electron Micrograph (SEM) of TMT934

4. Research on Functionality of TMT934 

1. Evaluation of the flowability and compressibility of powders

• Test samples: PH102 (MCC for direct compression), TMT934, and physical mixture of MCC and mannitol ("mixture" for short);

• Kawakita: n/C=n/a+1/ab (in which "a" refers to flowability constant, and "b" represents filling constant), used to judge the flowability and filling performance of powders;

• Test method: using a graduated cylinder to carry out an oscillation test of a certain volume of test powders, recording the number of oscillations and the volume of powders, and then comparing and analyzing different samples in terms of the flowability and filling performance by using Kawakita;

• Test results: 

Fig. 2 Kawakita of TMT934, PH102 and Physical Mixture

• Result analysis: TMT934 and PH102 (MCC for direct compression) are similar significantly superior to simple physical mixtures in flowability and filling performance. 

2. Research on formability

• Test samples: PH102 (MCC for direct compression), TMT934, and physical mixture of MCC and mannitol ("mixture" for short);

• Compressibility study: tensile strength by preforming under the same compression, and larger value means better compressibility of powders;

• Compactibility study: elastic recovery by preforming under the same compression, and smaller value means better compactibility of powders; 

    Fig.3 Relationship between Tensile Strength and Compression of TMT934, PH102, TF525 and Physical Mixture

Fig. 4 Relationship between Elastic Recovery and Compression of TMT934, PH102, TF525 and Physical Mixture

• Result analysis: the order of test samples by compressibility is TMT934＞Physical Mixture＞TF525＞PH102.

3. Low Lubricant Sensitivity Ratio (LSR)

• Test samples: PH102 (MCC for direct compression), and TMT934;

• LSR: lubricants could reduce the hardness of tablets, so a higher degree of sensitivity to lubricants means a greater softening effect; 

Fig. 5 LSR Test

• Result analysis: with the increase of lubricant concentration, the softening of PH102 aggravates, and TMT934 is less sensitive to lubricants compared with PH201. 

5. Conclusion of Research on Functionality of TMT934

The test results showed that co-processed excipient TMT934 is a new excipient with multiple outstanding properties. Its flowability is similar to that of PH102 (MCC for direct compression), and it's highly formable (better than Topchain Pharma's highly formable MCC TF525). Besides, the low sensitivity of TMT934 to lubricants can make lubricants less effective in softening tablets, so it's recommended for APIs that are sensitive to lubricants. Reply 934 to the background of the public account of Youpuhui for sample application.