(603r) Fluidized-Bed Impregnation of Active Pharmaceutical Ingredients Onto Porous Carriers

Impregnation is defined as the process of placing the chemical substances (including drugs) into the internal pores of a carrier. Impregnation of drugs onto porous carriers has been receiving increased attention in recent research activities, largely due to the drug dissolution profile change as a result of this process. Most of newly discovered drugs have poor solubility, so huge efforts have been applied to improve this problem. In impregnation, the solubility of drugs is improved by increasing the surface area of the drug. Furthermore, impregnation can improve the flow properties of drugs, which is very important in manufacturing of solid pharmaceuticals. Flow properties (i.e., cohesion, compressibility) affect mostly the content uniformity of the final dosage form. Assurance of content uniformity is very important especially for low dose drugs. The traditional method to improve flow properties is by the addition of lubricants and glidants. However, most of these additives have a negative impact on the dissolution of drugs because they are usually hydrophobic in nature. In impregnation, both dissolution and flow properties can be improved without the need of lubricants or glidants.

           In this work, the impregnation of Acetaminophen (APAP) into a magnesium/aluminum silicate (Neusilin ^R) has been studied using a Mini-Glatt spray fluidized bed dryer/granulator. Four different weight percent’s of APAP loading within the Neusilin: high (30%), medium (10%), low (1%) and ultra-low (0.1%), are examined. The experimental procedure includes 1) loading the fluidized bed with Neusilin until the top of the spray nozzle is reached, 2) warming up the Neusillin until a steady temperature is achieved, 3) spraying the APAP solution into the Neusilin, 4) drying the impregnated product. All the experimental conditions are kept constant except the APAP concentration. Ten Samples are taken from each experiment for characterization studies.

           The sample content uniformity is measured using UV-spectroscopy at ʎ=247.5.  Rotational shear testing is carried out in a FT4 powder rheometer to measure the sample flow properties. This test can be described briefly as the following: 1) A homogenous state is achieved by using rotating blades in a pre-conditioning step, 2) precompaction of the powder is effected using a vented piston, 3) the samples are sheared to obtain a yield point. This test has been carried out for both pure Neusilin and impregnated product to determine whether the flow properties of the impregnated product is affected by the presence of the drug or is only dependent on the pure carriers.