Evaluation Of Spheronized Pellets As Potential Matrix Sustained Release Dosage Form

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Date
1995-02
Authors
Bee Cheng, Lee
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Abstract
Satisfactory spherical pellets were successfully· prepared by the process of extrusionlspheronization using the excipient microcrystalline cellulose (IvrCC) as pellet-forming material. Nonetheless, the preparation of acceptable round spheres is highly dependent upon the attainment of an optimal formulation suited for this mcthod or proccssillg. The earlier part of the work has revealed that the MCe pellet system containing the active ingredientdiclofenac sodium generally produced strongly bonded spheroids which remained intact throughout the dissolution test. It may thus be postulated that the pellets behaved as an inert matrix system. The effecl of some excipients on the pellet quality and physical properties of diclofenac sodium-containing pellets was investigated. Certain disintegrants used , were fot~d to have a marked influence on the quality of the pellets. In addition, rapid pellet disintegration and dissolution were observed for the soybean oilformulated pellets, suggesting the potential of soybean oil as a disintegrating agent in pellet dosage form. However, when two other model drugs of varying aqueous solubilities, namely paracetamol and artemisinin, were separately incorporated into the soybean oil-containing formulations and compared, differences in the physical characteristics of the pellets such as disintegration and in vitro drug release were observed. The artemisinin-formulated pellets did not disintegrate and at the same time showed a considerably slower dissolution release rate than the pellets containing either diclofenac sodium or paracetamol, which are of higher aqueous solubilities. Since the former preparation exhibited no disintegration and produced an in vitro dissolution profile characteristic of sustained release products, it is apparent that the incorporated soybean oil failed to act as a disintegrant in the evident that both fast- and slow-release spherical pelleted products can be prepared via the extrusion/spheronization technique. In vivo evaluation of the artemisinin-containing preparation in five healthy human subjects, produced relatively uniform plasma concentration versus time profiles that were reflective of a slow and sustained rate of absorption. Moreover, the preparation showed a comparable extent of absorption than that of the drug administered as an aqueous suspension. Plasma concentrations of the drug wer~ determined using a developed HPLC method. A satisfactory correlation was obtained between the in vitro dissolution rate measurements and its in' vivo pharmacokinetic findings.
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Keywords
Spheronized Pellets , Dosage Form
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