Effect of formulation excipients and the manufacturing process for solid dosage form on the initial dissolution of theophylline

A model mixture of theophylline with two excipients (alpha -lactose monohyd rate and microcrystalline cellulose) was investigated in order to determine the influence of formulation and manufacturing process on the lyoavailabil ity of theophylline after compaction. After studying the role of individual excipients, the initial dissolution of a ternary blend (20% theophylline, 20% cellulose and 60% lactose), and a binary blend (20% theophylline and 80 % Cellactose) were analyled. It was demonstrated that associating two excip ients with different physical and mechanical proper-ties improved dissoluti on, whereas compact cohesion, linked to compaction pressure and excipient c haracteristics (Cellactose versus lactose/cellulose blend) limited dissolut ion. Dry manufacturing processes (dry granulation and direct compression) a ppeared to favor dissolution, while wet processes (wet granulation and extr usion-spheronization) produced condensed homogeneous associations of the th ree compounds that decreased theophylline dissolution; finally, reduction o f particle size by spray drying or grinding led to theophylline dissolution which was little sensitive to variations in compaction pressure.