Artigo

Solid Dispersion of Poorly Water-Soluble Drugs: Early Promises, Subsequent Problems, and Recent Breakthroughs
ABU T. M. SERAJUDDIN†
Contribution from Pharmaceutics R & D Department, Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, New Jersey 08903-0191. Received October 7, 1998. Accepted for publication July 15, 1999.
Abstract 0 Although there was a great interest in solid dispersion systems during the past four decades to increase dissolution rate and bioavailability of poorly water-soluble drugs, their commercial use has been very limited, primarily because of manufacturing difficulties and stability problems. Solid dispersions of drugs were generally produced by melt or solvent evaporation methods. The materials, which were usually semisolid and waxy in nature, were hardened by cooling to very low temperatures. They were then pulverized, sieved, mixed with relatively large amounts of excipients, and encapsulated into hard gelatin capsules or compressed into tablets. These operations were difficult to scale up for the manufacture of dosage forms. The situation has, however, been changing in recent years because of the availability of surface-active and self-emulsifying carriers and the development of technologies to encapsulate solid dispersions directly into hard gelatin capsules as melts. Solid plugs are formed inside the capsules when the melts are cooled to room temperature. Because of surface activity of carriers used, complete dissolution of drug from such solid dispersions can be obtained without the need for pulverization, sieving, mixing with excipients, etc. Equipment is available for large-scale manufacturing of such capsules. Some practical limitations of dosage form development might be the inadequate solubility of drugs in carriers and the instability of drugs and carriers at elevated temperatures necessary to manufacture capsules.

Figure 1sA schematic representation of the bioavailability enhancement of a poorly water-soluble