Microcrystalline Cellulose (Avicel PH 102): Directly compressible excipient. Magnesium Stearate: as a lubricant. Methods Experimental batches were prepared by mixing the active drug substance with a portion of either Lactose Anhydrous (LA), Microcrystalline Cellulose (MCC) or Starch 1500 (STA) and milled using a FitzMill through # 000 plate, impact forward at medium speed, in order to achieve distribution of the drug in the premix. The resultant premix was further mixed with the remainder of the excipient used and the other formulation ingredients (except for the lubricant) for 15 minutes and passed through a # 0 plate, knives forward at medium speed. Magnesium stearate was added and mixed for 5 minutes. The final granulation was compressed on a highspeed tablet press (Manesty B3B) equipped with 5⁄16” standard concave punches. Content uniformity studies were carried out on the experimental batches produced. CONTENT UNIFORMITY AND SEGREGATION STUDIES OF THE FINAL POWDER MIXTURES AND TABLETS Content Uniformity of the Final Powder Mixture Content uniformity testing was carried out by withdrawing at least 10 random samples using a sampling thief from different parts of the final powder mixture contained in the twin shell blender according to a validated sampling scheme. This scheme was adopted because it allows sample selection from: top, center, bottom and wall locations. In other words, it offers random representation of the entire powder blend. Samples selected were tested for their drug contents using an HPLC stability-indicating method. Content Uniformity of the Tablets Tablets were randomly selected from the beginning, middle and end of each compression run. 30 tablets were tested for their content uniformity using the HPLC stability-indicating method mentioned above. Segregation Studies The segregation tendency was investigated using a special segregation cell (Figure 1). This is represented by a special arrangement of stacking perspex (plastic) cylinders used to sample powder mixtures following stress under vibration. Powder mixture sampled randomly from the twin shell blender (( 50 g) was loaded into the segregation cell. The loaded segregation cell was then clamped to a Tapping Density Tester (from Vanderkamp) capable of applying low frequency vibration of 4Hz which mimics the vibration expected during tableting. 100 cycles of tapping were applied during the test. Following tapping, powder inside the perspex stacks was sampled consecutively using a spatula. Samples weighing 170 ( 1 mg (this corresponds to the tablet weight i.e. the scale of scrutiny) were tested for their drug contents using an HPLC stability-indicating method similar to the one used for testing powder mixtures and tablets. Results and Discussion Content uniformity data for the 3 formulations prepared using LA, STAor MCC as carriers for preparing active-premix are shown in Table 1. 2 MATERIALS Figure 1: A stack of Perspex Cylinders used a Part of the Segregation Cell Table 1: Data for Initial Experimental Studies Excipient used for Active-Premix Preparation Batch Size (Number of Tablets) Content Uniformity Mean Drug Content (%) ±RSD Final Powder Blend Tablets Lactose Anhydrous 200,000 82.20 ± 4.61 92.43 ± 1.42 Starch 1500 200,000 90.65 ± 3.89 96.00 ± 1.25 Avicel PH 102 200,000 98.52 ± 3.98 99.59 ± 3.19
Posted on: Fri, 05 Jul 2013 08:12:31 +0000
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