(105b) Adsorptive Precipitation from Supercritical Solutions in Aerogels: A Way Towards Stable Amorphous Drugs

Properties of solid materials are fundamentally determined by their crystallinity. In pharmaceutical technology the transition from amorphous to crystalline state plays an essential role, since the bioavailability of a drug is influenced by its state. Amorphous drugs often have higher bioavailability compare to the corresponding crystalline form. Tendency towards recrystallization is a major factor precluding more wide use of the amorphous drugs in solid dosage systems.

To overcome this problem, we study adsorptive precipitation of drugs and drug-like organic solids in aerogels. Adsorptive precipitation consists in immersion of a porous carrier in a drug solution in supercritical carbon dioxide (scCO₂) followed by rapid expansion of the solution. The latter causes precipitation of the drug in the carrier.

To reveal the influence of the drug nature, adsorptive precipitation experiments with various drugs were performed. Biopolymer and silica aerogels were used as porous carriers. Crystallinity and loading were assessed by XRD and UV spectrophotometry, respectively. The results along with literature data are discussed in order to reveal a key parameter that governs the stabilization of the amorphous state. The conclusion is that the drugâ??carrier interactions are crucial for the stabilization of amorphous state.

To quantify the interaction in scCO₂/drug/aerogel system, supercritical fluid chromatography (SFC) experiments were employed. Retention time was interpreted in the frame of vanâ??t Hoff analysis. Due to intense interactions, elution by pure scCO₂ was often not possible. In this case, a modifier (alcohol) was used. Foe such quaternary systems (scCO₂/modifier/drug/aerogel) a novel thermodynamic model (mixed retention model) was developed and validated. SFC experiments were carried out in the CO₂ density range of 0.40â??0.85 g/cm³. It was shown that CO₂ density plays an important role in drugâ??carrier interactions and changes the adsorption enthalpy by a factor of 2. Thus, by changing the density of the drug solution in sc-CO₂, it is possible to change the adsorption enthalpy of the drug on the carrier. Furthermore, it was found that the crystallinity of a model compound, naphthalene, measured by XRD is in an inverse relation to the adsorption enthalpy: the higher the enthalpy the lower the crystallinity.

To reveal the influence of the drug nature, SFC experiments were performed with various drugs. Biopolymer aerogels were used as carriers. The mixed retention model was applied to acquire enthalpy of adsorption from elution curves. Correlation between enthalpy of adsorption and crystallinity of the drugs is found and discussed along with literature data that considered to support our experimental findings.