Effect of Binder Type and Binder Level on the Properties of Agglomerates Containing Lactose and Dibasic Calcium Phosphate Dihydrate - Pharmaceutical Technology

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Effect of Binder Type and Binder Level on the Properties of Agglomerates Containing Lactose and Dibasic Calcium Phosphate Dihydrate
The authors studied the effect of the combination of binders on the flow and compressibility characteristics of the agglomerates of binary combination of lactose and dibasic calcium phosphate dihydrate.

Pharmaceutical Technology
Volume 32, Issue 10, pp. 54-64

Evaluation of agglomerates

Angle of repose. The angle of repose θ for each powder was determined by placing 30 g of the powder in a funnel. The tip of the orifice of the funnel was fixed and the powder was allowed to flow only under gravity. The angle of repose θ was calculated from the equation tan(θ) = h/r, in which h is the height of the pile of powder and r is the radius of the base of the cone (16).

Carr's index. Thirty grams of each sample were poured through a funnel into a 100-mL tarred graduated cylinder. The cylinder was then lightly tapped twice to collect all the powder sticking on the wall at the bottom of the cylinder. The volume was then read off directly from the cylinder and used to calculate the bulk density. For tap density, the cylinder was tapped from a height of 2.5 cm for 100 times on a wooden bench top before a constant reading was obtained. The percentage compressibility (Carr's index) was calculated as 100 times the ratio of the difference between tapped density and bulk density to the tapped density (17).

Evaluation of compressional characteristics

Preparation of blank tablets. The agglomerates (97%) of each batch of Plackett-Burman design were blended with 2% talc for 5 min and with 1% magnesium stearate for 2 min. Tablets were compressed by using 9-mm diameter flat-faced punches and die on a single–punch tablet machine (Cadmach Machinery Pvt. Ltd., Ahmedabad).

Crushing strength of blank tablets (CSB). The crushing strength of the tablets was determined after 24 h of compression, which allowed time for stress relaxation of the compression, using a tablet tester (Tablet Tester 8M, Dr. Schleuniger Pharmatron, Solothurn, Switzerland).

Preparation of tablets containing acetaminophen. The capacity of a direct-compression tablet diluent is the maximum proportion of other materials that can be mixed with it, while still obtaining tablets of acceptable quality. The capacity will depend on the nature of the materials added because the tableting properties of the drug itself will contribute to the overall tablet strength. Gohel et. al. have used acetaminophen as a model poorly compressible drug (10). Therefore, to test the capacity of the prepared agglomerates, tablets containing 30% acetaminophen were prepared. Tablets (n ≥ 50) containing acetaminophen (150 mg) and agglomerates of each run (350 mg), talc (10 mg), magnesium stearate (5 mg) were prepared on a single-punch tablet machine (Cadmach Machinery Ltd., Ahmedabad). The tablets containing acetaminophen were evaluated for crushing strength (CSP).

Table III: Composition of batches of agglomerates using a 23 factorial design, showing level of factors and their measured responses.
Optimization design. Based on the results of the screening experiment, three potential binders were identified to affect the properties of the agglomerates. These were further studied for optimization using a 23 factorial design, consisting of 3 binders at 2 levels. The design experiment was set up to investigate the effect of significant variables and their interactions on the agglomerates' characteristics. Table III shows the batch composition of the experimental design. The procedure followed for the preparation of the agglomerates was same as that used in the Plackett-Burman design. The agglomerates were evaluated for angle of repose and compressibility index. Blank tablets were prepared using agglomerates and evaluated for crushing strength (CSB). Tablets containing acetaminophen were prepared using 30% acetaminophen and 70% agglomerates, which were then evaluated for crushing strength (CSP).

Friability. Friability was evaluated as the percentage weight loss of 20 tablets tumbled in a friabilator (model EF2, Electrolab, India) for 4 min at 25 rpm. The tablets were dedusted, the loss in weight caused by fracture or abrasion was recorded, and the percentage friability was calculated (18).


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