Solid dispersion of poorly water‐soluble drugs: Early promises, subsequent problems, and recent breakthroughs

Abstract

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.

Biodegradable Self-Assembling PEG-Copolymer as Vehicle for Poorly Water-Soluble Drugs

“…Numerous approaches have been suggested to improve the oral bioavailability of poorly water-soluble drug candidates including micronization (particle size reduction), complexation, formation of a solid solution, preparation of amorphous solid oral dosage forms, lipid based systems (microemulsions, emulsions, liposomes), surfactant and polymer micelles, polymer-based systems (microparticles, microcapsules, etc. ), and many others (2)(3)(4)(5)(6)(7)(8).…”

Pharmaceutical Cocrystals: An Overview

“…A theoretical method based on K eu (the ratio of solution concentrations of cocrystal components at the eutectic point) was used to determine the cocrystals solubility in pure solvent and also a valuable tool for cocrystal selection and formulation without material and time requirement of traditional methods [42] . With the help of K eu , Serajuddin described the cocrystals solubility ratio and solution chemistry by using a set of more than 40 cocrystals and solvent combinations [43] . In one study, equations that describe cocrystal solubility in term of product solubility, cocrystal component ionization constants, and solution pH were derived for cocrystals with acidic, basic, amphoteric and zwitterionic components [12,44] .…”

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“…However, the use of high temperatures, and the fact that several drugs can be degraded by the melting process, can be a limitation of this method 44 . The incomplete miscibility between drug and carrier that may occur, because of the high viscosity of a polymeric carrier in the molten state, is another limitation of this process 45 .…”