Increasing drug solubility by means of bile salt–phosphatidylcholine-based mixed micelles

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 46; no. 3; pp. 361 - 367
• Main Authors: Hammad, M.A, Müller, B.W
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.11.1998; Elsevier Science
• Subjects: Benzodiazepines; Benzyl alcohol; Benzyl Alcohol - chemistry; Bile Acids and Salts - chemistry; Bile salt–phosphatidylcholine-mixed micelles; Biological and medical sciences; Chemistry, Pharmaceutical - methods; Drug Carriers; Drug Stability; General pharmacology; Medical sciences; Micelles; NMR study; Nuclear Magnetic Resonance, Biomolecular; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphatidylcholines - chemistry; Solubility; Solubilization; Steroidal drugs; Steroidal drugs; Benzyl alcohol; Bile salt–phosphatidylcholine-mixed micelles; Solubilization; NMR study; Benzodiazepines; Steroid; Delivery system; Pharmaceutical technology; Bile salt; Solubility; Mixed micelle; Drug carrier; In vitro; Tranquillizer; Dosage form; Phosphatidylcholine; Benzodiazepine derivatives
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/S0939-6411(98)00037-X

Study of the solubilization of commercial grades of soya phosphatidylcholine (SPC) with different purities by bile salts (BS) indicated that only highly pure grades of SPC are suitable for the preparation of clear solutions of BS/SPC-mixed micelles (BS/SPC-MM). The solubilizing capacity of different BS towards SPC increased in the following order; Sodium cholate (SC)<sodium deoxycholate (SDC)<sodium glycocholate (SGC). Moreover, egg phosphatidylcholine (EPC) was solubilized to a higher extent than SPC. Furthermore, the solubility study of different drugs in the prepared MM showed substantial enhancement of solubility, the extent of which is essentially affected by the chemical nature of the drug and the composition of MM. Benzodiazepine drugs such as clonazepam, tetrazepam, diazepam, and lorazepam displayed higher affinity for MM compared with BS alone, whereas steroidal drugs, such as estradiol, prednisolone and progesterone, compared with benzodiazepines, displayed relatively higher affinity for BS alone. The solubilizing capacity of MM for the different drugs was increased to different degrees by the addition of benzyl alcohol which was comparable to the solubility of the drug in pure benzyl alcohol. The interaction between benzyl alcohol and the drug in MM could be proved by NMR.