Prediction of Granule Physical Property by a Novel Compression Energy of Wet Powder

Abstract

Wet granulation is a significant process for handling powder materials. So far, many studies have been carried out to control the properties of granules. [1][2][3][4][5] In wet granulation, extrusion granulation is regarded as an appropriate method to easily obtain uniform physical properties. Extrusion granulation consists of kneading and extrusion, and it is well known that the condition of the kneaded material significantly influences the properties of the final products 6) as well as the condition of the extruder. However, the control of the kneading process has relied considerably on the operator's experience and ability to judge the condition of the wet powder by touching it. Therefore, a quantitative evaluation of the kneaded material is required for general process control.A formulation study is very important for stable manufacturing and maintaining the desired quality. The study includes the design of the dosage form and manufacturing process. Various types and amounts of additives should be examined to achieve the desired aspects such as dissolution, stability and manufacturing suitability. However, a hurdle to process development is that active pharmaceutical ingredients (API) are usually very expensive and their quantity is tiny. It is thus difficult to sufficiently examine the effects of various parameters. If the properties can be evaluated by a smaller sample quantity, significant savings in the cost, time and labor can be made, leading to the achievement of the optimal formulation.In our previous study, we have already reported that a compression test can easily evaluate the characteristics of a kneaded wet powder by using a small amount of sample. [7][8][9] In this study, the compression energy of the wet powder, which could represent its granular physical properties and characteristics of wet powder quantitatively, was used as a novel characteristic. ExperimentalPowder Materials Table 1 lists the powder materials used and Table 2 provides a summary of the formulations. Lactose monohydrate (DMV) was used as a filler, and hydroxypropylcellulose (Nippon Soda), microcrystalline cellulose (Asahi Kasei), low-substituted hydroxypropylcellulose (Shin-Etsu Chemical) and carmellose calcium (Gotoku Chemical) were used as the additives. Two grades of HPC-SSL and L-were used; SSL is less viscous than L. Two grades of L-HPC-LH11 and LH20-were also used; LH11 and LH20 differ in their degrees of substitution. LH20 is more substituted. These materials were mixed and kneaded with purified water in a planetary motion mixer (25AM-02-rr, DALTON Corporation). 1244Vol. 54, No. 9 Chem. Pharm. Bull. 54(9) 1244-1247 (2006) © 2006 Pharmaceutical Society of Japan * To whom correspondence should be addressed. e-mail: y-ohnishi@taiho.co.jp Wet granulation is a very important process and a reliable evaluation method for formulation study; thus it requires appropriate process control. In this study, a novel and effective method that involves a compression test of wet powder is proposed. Here, the compression energy, which...

Development of a Novel Tablet Machine for a Tiny Amount of Powder and Evaluation of Capping Tendency

“…However, in an early stage of formulation study, new active pharmaceutical ingredients (APIs) are generally very expensive and its available quantity is very tiny. 2,3) This strictly restricts a number of experiments and makes it difficult to sufficiently investigate the design space of a tableting process. Therefore, if tablets can be successfully prepared from a tiny amount of powder, it is possible to efficiently investigate its design space, resulting in significant cost reduction and speeding up of a new drug development.…”