Effects of cellulose derivatives and additives in the spray-drying preparation of acetaminophen delivery systems

Microcrystalline cellulose (MCC), sodium carboxymethylcellulose (NaCMC), hy droxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), hydroxyprop ylcellulose (HPC), and ethylcellulose (EC) were used for the production of time-controlled acetaminophen delivery systems using a spray-drilling techn ique. The influence of factors such as polymer concentration, inlet tempera ture, and drug/polymer ratio were investigated. The product yields were a f unction of the type and concentration of the polymer with the highest value s being reached from feeds containing 1% MCC and EC. Parameters of 1% polym er concentration and an inlet temperature of 140 degrees C gave rise to opt imal processing conditions. Using these parameters, the influence of some a djuncts, such as polyethylene glycol 6000 (PEG 6000), dibutyl sebacate (DBS ), polyvinylpyrrolidone (PVP), and carboxylic acids such as citric acid (CA ), phthalic acid (PA), succinic acid (SA), tartaric acid (TA), and oxalic a cid (OA), on the spray-drying process was evaluated. Of the additives teste d PVP (with MCC), DBS (with EC), and PEG 6000 (with NaCMC) induced yield de creases from 70% to 49%, 66% to 39%, and 37% to 17%, respectively. As for c arboxylic acids (with NaCMC), similar or better performances of 43%, 45%, 4 7%, and 49% were obtained with SA, OA, PA, and TA, respectively. Dissolutio n studies in pH I dilute HCl and pH 6.8 phosphate buffer dissolution media showed that formulations consisting of 1% polymer with a drug/polymer ratio of 1/1 exhibited the slowest drug release, with the spheroids coated with NaCMC and HEC showing the longest T-50% values (with 45 and 53 min at pH I and 49 and 55 min at pH 6.8, respectively). Slightly better sustained drug release in pH 6.8 dissolution medium was reached, showing the following tre nd: HEC > NaCMC > MCC > EC > HPMC. Concerning the additives, the trends in dissolution T-50% of drug revealed TA > SA > CA > OA > PVP > PA > DBS in ac idic pH I dissolution medium and PVP > OA > TA > SA > PA > CA > DBS in phos phate buffer at pH 6.8.