Billon A, Petit M, Doko M B, Bataille B, Jacob M
Université Montpellier I, Faculté de Pharmacie, Laboratoire de Pharmacie Galénique, Pharmacotechnie et Biopharmacie, France.
Drug Dev Ind Pharm. 1999 Nov;25(11):1149-56. doi: 10.1081/ddc-100102282.
Microcrystalline cellulose (MCC), sodium carboxymethylcellulose (NaCMC), hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), and ethylcellulose (EC) were used for the production of time-controlled acetaminophen delivery systems using a spray-drying technique. The influence of factors such as polymer concentration, inlet temperature, and drug/polymer ratio were investigated. The product yields were a function of the type and concentration of the polymer, with the highest values being reached from feeds containing 1% MCC and EC. Parameters of 1% polymer concentration and an inlet temperature of 140 degrees C gave rise to optimal processing conditions. Using these parameters, the influence of some adjuncts, 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 acid (OA), on the spray-drying process was evaluated. Of the additives tested, PVP (with MCC), DBS (with EC), and PEG 6000 (with NaCMC) induced yield decreases from 70% to 49%, 66% to 39%, and 37% to 17%, respectively. As for carboxylic acids (with NaCMC), similar or better performances of 43%, 45%, 47%, and 49% were obtained with SA, OA, PA, and TA, respectively. Dissolution studies in pH 1 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 T50% values (with 45 and 53 min at pH 1 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 trend: HEC > NaCMC > MCC > EC > HPMC. Concerning the additives, the trends in dissolution T50% of drug revealed TA > SA > CA > OA > PVP > PA > DBS in acidic pH 1 dissolution medium and PVP > OA > TA > SA > PA > CA > DBS in phosphate buffer at pH 6.8.
使用喷雾干燥技术，将微晶纤维素（MCC）、羧甲基纤维素钠（NaCMC）、羟丙基甲基纤维素（HPMC）、羟乙基纤维素（HEC）、羟丙基纤维素（HPC）和乙基纤维素（EC）用于制备定时释放对乙酰氨基酚的给药系统。研究了聚合物浓度、进口温度和药物/聚合物比例等因素的影响。产品收率是聚合物类型和浓度的函数，含1%MCC和EC的进料收率最高。聚合物浓度为1%、进口温度为140℃的参数产生了最佳加工条件。使用这些参数，评估了一些辅料，如聚乙二醇6000（PEG 6000）、癸二酸二丁酯（DBS）、聚乙烯吡咯烷酮（PVP）以及柠檬酸（CA）、邻苯二甲酸（PA）、琥珀酸（SA）、酒石酸（TA）和草酸（OA）等羧酸对喷雾干燥过程的影响。在所测试的添加剂中，PVP（与MCC一起）、DBS（与EC一起）和PEG 6000（与NaCMC一起）导致收率分别从70%降至49%、66%降至39%和37%降至17%。至于羧酸（与NaCMC一起），SA、OA、PA和TA分别获得了43%、45%、47%和49%的相似或更好的性能。在pH 1稀盐酸和pH 6.8磷酸盐缓冲液溶解介质中的溶出度研究表明，由1%聚合物和药物/聚合物比例为1/1组成的制剂药物释放最慢，涂有NaCMC和HEC的球体显示出最长的T50%值（在pH 1时分别为45和53分钟，在pH 6.8时分别为49和55分钟）。在pH 6.8溶解介质中达到了稍好的药物缓释效果，呈现以下趋势：HEC＞NaCMC＞MCC＞EC＞HPMC。关于添加剂，在酸性pH 1溶解介质中药物溶出T50%的趋势为TA＞SA＞CA＞OA＞PVP＞PA＞DBS，在pH 6.8磷酸盐缓冲液中为PVP＞OA＞TA＞SA＞PA＞CA＞DBS。
