PURPOSE: To examine whether the small quantities of lipid present in unit-dose microemulsion formulations comprising medium- (C8-10) or long-chain (C18) glyceride lipids can stimulate the intestinal lymphatic transport of halofantrine (Hf), a model lymphatically transported drug. METHODS: Hf (50 mg) was administered to thoracic lymph duct- and cephalic vein-cannulated fasted greyhound dogs. Drug was formulated as a single soft gelatin capsule containing approximately 1 g of a microemulsion preconcentrate based on either medium- or long-chain glycerides. Thoracic lymph was collected, and systemic plasma samples taken over 10 h postdose. RESULTS: The extent of lymphatic transport of Hf after administration of the long-chain lipid formulation was high (28.3% of dose), and significantly higher than that seen after administration of the medium-chain formulation (5.0% of dose). Plasma levels of Hf were not significantly different across the two formulations when assessed by AUC0-10h. CONCLUSIONS: This is the first study to demonstrate that the small amounts of lipid present within a single lipid-based dose form can support substantial intestinal lymphatic transport in the fasted state. Furthermore, microemulsions based on long-chain glycerides appear to be more effective with respect to lymphatic transport than the equivalent medium-chain formulation.
PURPOSE: To examine whether the small quantities of lipid present in unit-dose microemulsion formulations comprising medium- (C8-10) or long-chain (C18) glyceride lipids can stimulate the intestinal lymphatic transport of halofantrine (Hf), a model lymphatically transported drug. METHODS:Hf (50 mg) was administered to thoracic lymph duct- and cephalic vein-cannulated fasted greyhound dogs. Drug was formulated as a single soft gelatin capsule containing approximately 1 g of a microemulsion preconcentrate based on either medium- or long-chain glycerides. Thoracic lymph was collected, and systemic plasma samples taken over 10 h postdose. RESULTS: The extent of lymphatic transport of Hf after administration of the long-chain lipid formulation was high (28.3% of dose), and significantly higher than that seen after administration of the medium-chain formulation (5.0% of dose). Plasma levels of Hf were not significantly different across the two formulations when assessed by AUC0-10h. CONCLUSIONS: This is the first study to demonstrate that the small amounts of lipid present within a single lipid-based dose form can support substantial intestinal lymphatic transport in the fasted state. Furthermore, microemulsions based on long-chain glycerides appear to be more effective with respect to lymphatic transport than the equivalent medium-chain formulation.
Authors: Shui-Mei Khoo; Richard J Prankerd; Glenn A Edwards; Christopher J H Porter; William N Charman Journal: J Pharm Sci Date: 2002-03 Impact factor: 3.534
Authors: Magesh Muthu; Jaganmohan Somagoni; Vino T Cheriyan; Sara Munie; Edi Levi; Abdelkader E Ashour; Alaa Eldeen B Yassin; Ahmed M Alafeefy; Paula Sochacki; Lisa A Polin; Kaladhar B Reddy; Scott D Larsen; Mandip Singh; Arun K Rishi Journal: J Biomed Nanotechnol Date: 2015-09 Impact factor: 4.099
Authors: Natalie L Trevaskis; David M Shackleford; William N Charman; Glenn A Edwards; Anne Gardin; Silke Appel-Dingemanse; Olivier Kretz; Bruno Galli; Christopher J H Porter Journal: Pharm Res Date: 2009-03-12 Impact factor: 4.200
Authors: Natalie L Trevaskis; Suzanne M Caliph; Gary Nguyen; Patrick Tso; William N Charman; Christopher J H Porter Journal: Pharm Res Date: 2013-02-21 Impact factor: 4.200
Authors: Atheer Zgair; Jonathan Cm Wong; Jong Bong Lee; Jatin Mistry; Olena Sivak; Kishor M Wasan; Ivo M Hennig; David A Barrett; Cris S Constantinescu; Peter M Fischer; Pavel Gershkovich Journal: Am J Transl Res Date: 2016-08-15 Impact factor: 4.060
Authors: Natalie L Trevaskis; Claire L McEvoy; Michelle P McIntosh; Glenn A Edwards; Ravi M Shanker; William N Charman; Christopher J H Porter Journal: Pharm Res Date: 2010-03-11 Impact factor: 4.200