Hydration of an amphiphilic excipient, Gelucire 44/14.
The incorporation of drugs into Gelucires has been reported to increase the dissolution rate of poorly soluble drugs, often leading to improved drug bioavailability. In pharmaceutical applications, it is important to know how the excipient interacts with the drug, and how the mixture behaves during manufacturing, storage as well as during administration. The uptake of water by an amphiphilic excipient, Gelucire 44/14, has been investigated in two ways: storage in humid air and addition of liquid water. During exposure to humid air, the uptake goes in stages that correspond to the dissolution of the components of the excipient, starting with the most hydrophilic ones: glycerol, then polyethylene glycol (PEG), PEG esters (PEG monolaurate and PEG dilaurate), and finally glycerides (trilaurin). At each stage, the remaining crystals are in equilibrium with an interstitial solution made of water and the dissolved components. In this range of hydrations, the total uptake is close to the sum of the equilibrium hydrations of the components. In the pharmaceutical formulation, the active ingredient could dissolve in the liquid phase. At larger hydrations, obtained through addition of liquid water, the state of Gelucire 44/14 differs from those of its components. Gelucire 44/14 forms a lamellar phase and this phase melts at 30 degrees C whereas the pure PEG esters form hexagonal and cubic mesophases. The cubic mesophases do not melt until the temperature exceeds 40 degrees C. At body temperature, all crystals in Gelucire 44/14 melt to an isotropic fluid as soon as the total water content exceeds 5%. Therefore the formulation of amphiphilic excipients can be optimized to avoid the formation of mesophases that impede dissolution of the excipient at body temperature.
Svensson
A
A
Food technology, Chemical Center, Lund University, POB 124, S 221 00, Sweden.
Neves
C
C
Cabane
B
B
D001826:Body Fluids / Q000737:chemistry / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D003460:Crystallization; D003890:Desiccation / Q000379:methods; D004055:Differential Thermal Analysis / Q000379:methods; D004356:Drug Storage / Q000379:methods; D005079:Excipients / Q000737:chemistry* / Q000493:pharmacokinetics*; D005544:Forecasting; D005990:Glycerol / Q000737:chemistry; D006813:Humidity; D057927:Hydrophobic and Hydrophilic Interactions; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics*; D013696:Temperature; D014280:Triglycerides / Q000737:chemistry / Q000493:pharmacokinetics; D014867:Water / Q000737:chemistry*; D017155:Wettability; D014961:X-Ray Diffraction / Q000379:methods
D005079:Excipients; D014280:Triglycerides; D014867:Water; C104509:gelucire 44-14; D011092:Polyethylene Glycols; C004565:trilaurin; D005990:Glycerol