Kaukonen Ann Marie, Boyd Ben J, Charman William N, Porter Christopher J H
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University (Parkville Campus), Parkville, Victoria 3052, Australia.
Pharm Res. 2004 Feb;21(2):254-60. doi: 10.1023/b:pham.0000016283.87709.a9.
The purpose of this study was to characterize the solubilization and precipitation characteristics of a range of poorly water-soluble drugs during the in vitro digestion of long-chain or medium-chain triglyceride (TG) lipid suspension formulations.
TG suspensions of model drugs (present at double their equilibrium solubilities in the respective lipid) were digested in vitro and the drug solubilization and precipitation pattern in the resulting digests analyzed.
For griseofulvin, diazepam, and danazol, solubilization of the small mass of drug originally presented in the TG lipid was efficient with only a small proportion of the dose precipitating and being recovered in the pellet phase after digestion of the TG lipid. For the more lipophilic and lipid-soluble drugs (cinnarizine, halofantrine), in which higher drug loadings were possible, significant enhancement in drug solubilization in the postdigestion aqueous phase was not apparent compared with simple TG lipid solutions.
Suspensions of drugs, which are poorly soluble in water and TG lipid, may prove beneficial as the relatively high solubilizing capacity of the colloidal phases produced on TG digestion will likely exceed the mass of drug that could have been administered as a simple lipid solution. However, for more lipid-soluble drugs, suspension formulations may offer little benefit as sufficiently high drug loadings can otherwise be achieved with simple solution formulations that still provide for adequate solubilization after TG digestion.
本研究旨在表征一系列难溶性药物在长链或中链甘油三酯（TG）脂质混悬液制剂体外消化过程中的增溶和沉淀特性。
将模型药物的TG混悬液（药物含量为其在相应脂质中平衡溶解度的两倍）进行体外消化，并分析所得消化液中药物的增溶和沉淀模式。
对于灰黄霉素、地西泮和达那唑，最初存在于TG脂质中的少量药物增溶效果良好，TG脂质消化后只有一小部分剂量沉淀并在沉淀相中回收。对于亲脂性和脂溶性更高的药物（桂利嗪、卤泛群），由于可以实现更高的药物负载量，与简单的TG脂质溶液相比，消化后水相中药物增溶的显著增强并不明显。
难溶于水和TG脂质的药物混悬液可能是有益的，因为TG消化产生的胶体相相对较高的增溶能力可能会超过以简单脂质溶液形式给药的药物量。然而，对于脂溶性更高 的药物，混悬液制剂可能益处不大，因为通过简单溶液制剂可以实现足够高的药物负载量，并且在TG消化后仍能提供足够的增溶作用。
