The role of the carrier in the formulation of pharmaceutical solid dispersions. Part I: crystalline and semi-crystalline carriers.
As a consequence of the target and drug candidate identification process, drugs with higher hydrophobicity and/or lipophilicity are being selected for further development, leading to solubility and dissolution rate limited oral bioavailability, and hence potential failure of the intended therapeutic goal. Solid dispersions were introduced as a formulation strategy in the early 1960s to tackle this issue and are still an area of intensive research activity. Areas covered: There has been a shift in the type of carriers that were used in the formulation of solid dispersions as nowadays, amorphous carriers are most often used, whereas in early stages of solid dispersions development, crystalline and semi-crystalline carriers were most commonly applied. In this review, we will discuss several aspects related to the use of crystalline and semi-crystalline carriers such as their molecular and related physical structure, and their physical chemical properties related to formulation of poorly soluble drugs. Expert opinion: The inherent crystallinity of this type of carrier hinders the formation of high-load solid solutions as mainly the amorphous domains of a carrier are able to accommodate drug molecules. Hence these carriers are not currently first choice excipients to formulate solid dispersions.
a Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition , KU Leuven - University of Leuven , Leuven , Belgium.|b Department of Pharmaceutics , Hanoi University of Pharmacy , Ha Noi , Vietnam.
Tu
T
Van Duong
a Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition , KU Leuven - University of Leuven , Leuven , Belgium.
Guy
G
Van den Mooter
D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D012995:Solubility
D004337:Drug Carriers; D005079:Excipients
Citric acid; crystalline carrier; mannitol; microstructure; polyethylene glycol; poorly soluble drugs; semi-crystalline carrier; solid dispersions; urea