Formation of nano/micro-dispersions with improved dissolution properties upon dispersion of ritonavir melt extrudate in aqueous media.
The objective of the study was to characterise the aqueous dispersions of ritonavir melt extrudates. More specifically to look into the particular system formed when melt extrudate of a poorly soluble drug dissolved in a hydrophilic polymer matrix containing a surfactant is dispersed in an aqueous medium. Melt extrudates with and without ritonavir were studied. The drug containing extrudate was confirmed to be molecular dispersions of drug in a polymer/surfactant matrix. Particulate dispersions were formed in water from both drug and placebo extrudates. The dispersions were investigated with respect to mean particle size and particle size distribution (photon correlation spectroscopy and optical particle counting), surface charge (zeta potential), particle composition (ultracentrifugation), tendency to form aggregates and precipitate (turbidity), in vitro dissolution rate and drug release. It was concluded that dispersion of melt extrudates in aqueous medium give rise to nano/micro-dispersions. The stability of the nano/micro-dispersion is sensitive to anions and may be subjected to association/aggregation/flocculation as time proceeds after preparation of dispersion. Melt extrudate showed improved dissolution rate and drug release properties compared to crystalline raw material. From studies of single components and physical mixtures of the formulation composition it can be concluded that the drug delivery system itself, namely solid dispersion prepared by melt extrusion technology, plays a key role for the formation of the observed particles.
Tho
Ingunn
I
Drug Transport and Delivery Group, Dept. of Pharmacy, University of Tromsoe, N-9037 Tromsoe, Norway. ingunn.tho@uit.no
Liepold
Bernd
B
Rosenberg
Joerg
J
Maegerlein
Markus
M
Brandl
Martin
M
Fricker
Gert
G
D001682:Biological Availability; D002021:Buffers; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004355:Drug Stability; D006601:Hexoses / Q000737:chemistry; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry*; D009391:Nephelometry and Turbidimetry; D009994:Osmolar Concentration; D010316:Particle Size; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D019438:Ritonavir / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D012822:Silicon Dioxide / Q000737:chemistry; D012995:Solubility; D055672:Static Electricity; D013501:Surface-Active Agents / Q000737:chemistry; D013656:Taurocholic Acid / Q000737:chemistry; D014867:Water / Q000737:chemistry*
D002021:Buffers; D004337:Drug Carriers; D006601:Hexoses; D014677:Pharmaceutical Vehicles; D011145:Polyvinyls; D013501:Surface-Active Agents; D014867:Water; C013215:polyvinyl acetate; D013656:Taurocholic Acid; C014822:sorbitan monolaurate; D012822:Silicon Dioxide; D011205:Povidone; D019438:Ritonavir