Guhmann Marie, Preis Maren, Gerber Frédéric, Pöllinger Norbert, Breitkreutz Jörg, Weitschies Werner
Department of Pharmacy, Institute of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald , Greifswald , Germany .
Drug Dev Ind Pharm. 2015 Apr;41(4):540-51. doi: 10.3109/03639045.2014.884122. Epub 2014 Feb 5.
Fast onset of action is prerequisite for acute pain medication. A palatable orodispersible medicine of diclofenac providing rapid analgesic effect should improve patient compliance and treatment.
In the present study, diclofenac taste-masked orodispersible tablets (ODTs) with fast release characteristics were developed. Different taste-masking approaches and formulation concepts were screened in vitro for candidate selection.
Diclofenac was used as free acid. Five taste-masked microgranule formulations were prepared by wet granulation and/or coating processes, and compressed to ODTs. Citric acid (pH-modifying agent) and Eudragit® E PO (amino methacrylate copolymer) were used as taste-masking agents. Evaluation criteria were (i) disintegration time, (ii) processability and (iii) in-vitro dissolution profiles in simulated saliva (pH 7.4, 5 mL, 3 min) and compendial pH-change media (paddle, 50 rpm). The prototypes were compared to reference ODTs (without taste-masking). Most suitable ODT prototypes were selected and further evaluated for taste-masking efficiency using an electronic tongue.
In simulated saliva, the drug was slower released from the prototypes (between 1.1% and 15.5%) than from reference ODTs (23.7%). Less dissolved particles are thus expected in vivo for taste perception. Two ODT prototypes showed fast and complete drug release in phosphate buffer. The formulation providing the most efficient taste-masking was selected guided by electronic tongue data.
A novel palatable and fast acting diclofenac ODT formulation was successfully developed. Formulation design, development and in-vitro evaluation used in this study may serve as rational approach for manufacturing taste-masked orodispersible dosage forms.
快速起效是急性疼痛药物治疗的前提条件。一种口感良好的双氯芬酸口腔崩解片，若能提供快速镇痛效果，将有助于提高患者的依从性和治疗效果。
在本研究中，研发了具有快速释放特性的双氯芬酸掩味口腔崩解片（ODT）。通过体外筛选不同的掩味方法和制剂概念，以进行候选物选择。
使用双氯芬酸游离酸。通过湿法制粒和/或包衣工艺制备了五种掩味微颗粒制剂，并压制成口腔崩解片。柠檬酸（pH调节剂）和Eudragit® E PO（甲基丙烯酸氨基共聚物）用作掩味剂。评价标准包括：（i）崩解时间；（ii）可加工性；（iii）在模拟唾液（pH 7.4，5 mL，3分钟）和药典规定的pH变化介质（桨法，50转/分钟）中的体外溶出曲线。将原型制剂与对照口腔崩解片（未掩味）进行比较。选择最合适的口腔崩解片原型，并用电子舌进一步评估其掩味效率。
在模拟唾液中，原型制剂中药物的释放速度（1.1%至15.5%之间）比对照口腔崩解片（23.7%）慢。因此，预计体内用于味觉感知的溶解颗粒较少。两种口腔崩解片原型在磷酸盐缓冲液中显示出快速且完全的药物释放。根据电子舌数据选择了掩味效果最佳的制剂。
成功研发出一种新型口感良好且起效迅速的双氯芬酸口腔崩解片制剂。本研究中使用的制剂设计、研发和体外评价方法，可作为制备掩味口腔崩解剂型的合理方法。
