Development of spray-dried acetaminophen microparticles using experimentaldesigns

Experimental factorial designs were built to investigate the effects of fiv e parameters on production yields and moisture contents of spray-dried prod ucts. These factors concerned both the solution feed (drug concentration, c olloidal silica concentration and polymer/drug ratio) and the spray dryer ( inlet temperature and feed rate). Three formulations containing cellulose d erivatives and acetaminophen were tested. The aim of the study was to optim ize the operating conditions to maximize production yields while minimizing moisture contents. First screening experiments consisting of fractional fa ctorial designs revealed the most significant factors to be inlet temperatu re, feed rate and their interaction for both formulations containing sodium carboxymethylcellulose and feed rate and colloidal silica concentration fo r the formulation containing microcrystalline cellulose. Then, the optimal operating conditions were estimated by response surface methodology. Centra l rotational composite designs showed quadratic models were adequate. New a ssays were carried out using these last conditions to evaluate both the rep eatability and reproducibility of the spray-drying technique. Yields above 80% and moisture content of similar to 1% were reached. The characterizatio n of microparticles revealed the poor flowability of the spray-dried produc ts due to significant cohesiveness and very small size (less than 55 mu m). (C) 2000 Published by Elsevier Science B.V. All rights reserved.