Solid dispersion drug stabilization

Doherty, C. and York, P. (1989). Accelerated stability of an x-ray amorphous frusemide-PVP solid dispersion, Drug Dev. Ind. Pharm., 15 1969-1987. 

Both chemical and physical stability must be assured in the development of solid dispersions. Since the drug is either molecularly dispersed or intimately mixed with the carrier, there is potential for greater chemical interaction between them. Any physical instability that leads to phase transformations may result in poor performance of dosage forms, including changes in dissolution rates and oral bioavailability. 

First, evaluate the feasibility of solid dispersion such as a polyethylene glycol (PEG)-based semisolid or solid hard gelatin capsule formulation.32 33 When the molecular weight of PEG used in the formulation is greater than 3350 Da, PEG exists as a solid. Prerequisites for this formulation approach include (1) adequate solubility and (2) thermal-stability of the drug in molten PEG during processing. 

Goracinova K, Klisarova L, Simov A, et al. Preparation, physical characterization, mechanisms of drug/polymer interactions, and stability studies of controlled-release solid dispersion granules containing weak base as active substance. Drug Dev Ind Pharm 1996 22(3) 255-262. 

Spray drying of a nonaqueous system has also been shown, a Gelucire 50/13 based solid dispersions have been prepared to stabilize and improve in vivo performance of hydrophobic drugs (79,80). 

As the active substance in a solid solution is in an amorphous state and therefore in a more energetic form, and as its surface area is much greater both in solid solutions and in solid dispersions, the question of its physical and chemical stability arises. The main criterion for physical stability is the extent of recrystallization, which can reduce the bioavailability of the active substance. Surprisingly, a survey of publications in which recrystallization and chemical stability have been investigated reveals only relatively few cases of instability. Table 80 contains a list of publications with stability data for solid solutions of drugs in povidone with a... 

It is also important to note that each of these dispersions can be exploited to enhance the delivery of the drug substance. For example, the majority of dissolution enhanced products are prepared in the amorphous state to leverage the higher solubility of the material and increase release rates from the drug product. Furthermore, the homogeneous nature of the dispersion provides a kinetic barrier for recrystallization of the amorphous form that contributes to improved physical stability. However, in the case of controlled release and directly shaped products where the systems may be prepared to have specific structural and mechanical attributes, the use of solid dispersions wherein both the drug and polymer exist as crystalline materials within the system may be beneficial. 

---