GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Meggle Singapore, 45 Jalan Pemimpin, #06-00 Foo Wah Industrial Building, Singapore 577197, Singapore.
Int J Pharm. 2018 Dec 20;553(1-2):229-237. doi: 10.1016/j.ijpharm.2018.10.040. Epub 2018 Oct 16.
Knowledge on the dissolution behaviour of a drug is critical for efficient and effective product development. As the drug has almost always to be formulated with excipients in the design of a dosage form, it is important to examine the implications of the choice of excipients on the dissolution of the drug, among others, especially in the case of an immediate release dosage form. The objective of this study was to explore the potential of using an ultraviolet (UV) imaging technique to examine the effect of drug-excipient ratio on the initial dissolution of the drug, when formulated with a hydrophilic, water insoluble excipient. A series of drug-excipient binary blends with different ratios were prepared and compacted into 2 mm compacts, and their dissolution profiles captured with a UV imager. Chemical imaging via Raman spectroscopy was also performed on the compacts to quantify the fraction of drug presented on the compact surface. At low drug concentrations, a suppression in drug dissolution was observed, but beyond a critical drug-excipient ratio, the concentration of the excipient no longer played a role in affecting drug dissolution rates. Drug particle size was found to affect the critical drug-excipient ratio required to negate the shielding effect exerted by the excipient, such that a higher proportion of drug was required. It is postulated that the excipient served as a physical barrier, as well as competitor for water required for wetting during initial dissolution, thereby causing a delay in the wetting and dissolution of the drug.
药物的溶解行为知识对于高效、有效的产品开发至关重要。由于在设计剂型时药物几乎总是要与赋形剂一起配制，因此检查赋形剂的选择对药物溶解的影响非常重要，特别是在速释剂型的情况下。本研究的目的是探索使用紫外（UV）成像技术检查药物-赋形剂比例对亲水性、水不溶性赋形剂配制的药物初始溶解的影响的潜力。制备了一系列不同比例的药物-赋形剂二元混合物，并将其压制成 2mm 的片剂，并用 UV 成像仪捕获其溶解曲线。还对片剂进行了拉曼光谱化学成像，以定量计算片剂表面存在的药物分数。在低药物浓度下，观察到药物溶解受到抑制，但超过临界药物-赋形剂比例后，赋形剂的浓度不再影响药物溶解速率。发现药物粒径会影响抵消赋形剂屏蔽作用所需的临界药物-赋形剂比例，因此需要更高比例的药物。推测赋形剂既是物理屏障，也是初始溶解过程中润湿所需水的竞争者，从而导致药物润湿和溶解延迟。
