Wong S M, Kellaway I W, Murdan S
School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, United Kingdom.
Int J Pharm. 2006 Jul 6;317(1):61-8. doi: 10.1016/j.ijpharm.2006.03.001. Epub 2006 May 2.
The slow dissolution rate exhibited by poorly water-soluble drugs is a major challenge in the drug development process. Following oral administration, drugs with slow dissolution rates generally show erratic and incomplete absorption which may lead to therapeutic failure. The aim of this study was to improve the dissolution rate and subsequently the oral absorption and bioavailability of a model poorly water-soluble drug. Microparticles containing the model drug (griseofulvin) were produced by spray drying the drug in the absence/presence of a hydrophilic surfactant. Poloxamer 407 was chosen as the hydrophilic surfactant to improve the particle wetting and hence the dissolution rate. The spray dried particles were characterized and in vitro dissolution studies and in vivo absorption studies were carried out. The results obtained showed that the dissolution rate and absolute oral bioavailability of the spray dried griseofulvin/Poloxamer 407 particles were significantly increased compared to the control. Although spray drying griseofulvin alone increased the drug's in vitro dissolution rate, no significant improvement was seen in the absolute oral bioavailability when compared to the control. Therefore, it is believed that the better wetting characteristics conferred by the hydrophilic surfactant was responsible for the enhanced dissolution rate and absolute oral bioavailability of the model drug.
水溶性差的药物所表现出的缓慢溶解速率是药物研发过程中的一个主要挑战。口服给药后，溶解速率缓慢的药物通常显示出不稳定且不完全的吸收，这可能导致治疗失败。本研究的目的是提高一种典型的水溶性差的药物的溶解速率，进而提高其口服吸收和生物利用度。通过在不存在/存在亲水性表面活性剂的情况下喷雾干燥该药物来制备含有模型药物（灰黄霉素）的微粒。选择泊洛沙姆407作为亲水性表面活性剂以改善颗粒的润湿性，从而提高溶解速率。对喷雾干燥的颗粒进行了表征，并开展了体外溶出度研究和体内吸收研究。所得结果表明，与对照相比，喷雾干燥的灰黄霉素/泊洛沙姆407颗粒的溶解速率和绝对口服生物利用度显著提高。尽管单独喷雾干燥灰黄霉素提高了药物的体外溶解速率，但与对照相比，绝对口服生物利用度未见显著改善。因此，据信亲水性表面活性剂赋予的更好润湿性是模型药物溶解速率和绝对口服生物利用度提高的原因。
