PDF(Pubmed)
Abstract：
Swallowing oral solid dosage forms is challenging for those who have medication swallowing difficulties, including patients with dysphagia. One option is to mix the drug (whole or crushed) with a thick vehicle (medication lubricant). Previous in vitro studies consistently suggest that thick vehicles could impact the dissolution of solid dosage forms, potentially influencing their therapeutic effectiveness, but do not account for changes that happen during oral processing and swallowing. This study aims to investigate the potential impact of medication lubricants on drug release and examine the effect of oral processing. In vitro dissolution of whole and crushed paracetamol tablets mixed with five commercially available medication lubricants (two IDDSI level 2, two IDDSI level 3, and one IDDSI level 4) were tested with and without oral processing; a medication lubricant with/without paracetamol was placed in the mouth (five healthy volunteers), prepared for swallowing, but then expectorated and assessed for physical characteristics and drug release. Medication lubricants, both alone and mixed with crushed paracetamol tablets, showed a significant decrease in viscosity after oral processing. Without oral processing, IDDSI level 3 and 4 lubricants significantly delayed the dissolution of paracetamol tablets. After oral processing, particularly with crushed tablets, there was a substantial increase in the dissolution rate. These findings suggest that dissolution testing overestimates the impact of medication lubricants on drug dissolution. Therefore, using in vitro dissolution tests to predict the dissolution rate of medications mixed with thick vehicles is discouraged. It is essential to consider ways to incorporate the effects of the oral environment and oral processing on thick vehicles used for oral medication administration.
摘要：
吞咽口服固体剂型对于那些有药物吞咽困难的人来说是具有挑战性的。包括吞咽困难的患者。一种选择是将药物（全部或压碎的）与厚载体（药物润滑剂）混合。以前的体外研究一致表明，厚载体可能会影响固体剂型的溶出度，可能影响他们的治疗效果，但不考虑口腔处理和吞咽过程中发生的变化。这项研究旨在研究药物润滑剂对药物释放的潜在影响，并检查口服处理的效果。在有和没有口服处理的情况下，测试了与五种市售药物润滑剂（两种IDDSI2级，两种IDDSI3级和一种IDDSI4级）混合的完整和压碎的扑热息痛片剂的体外溶出；将含/不含扑热息痛的药物润滑剂放入口中（五名健康志愿者），准备吞咽，然后吐出并评估身体特征和药物释放。药物润滑剂，单独和与扑热息痛片混合，口服处理后粘度显着降低。没有口腔处理，IDDSI3级和4级润滑剂显著延迟扑热息痛片剂的溶解。经口处理后,特别是压碎的药片，溶出度大幅增加。这些发现表明溶出度测试高估了药物润滑剂对药物溶出度的影响。因此,不鼓励使用体外溶出试验来预测与浓载体混合的药物的溶出速率。必须考虑将口腔环境和口腔处理的影响纳入用于口服药物给药的厚载体的方法。
