Amorphous and Crystalline Particulates: Challenges and Perspectives in Drug Delivery

Abstract

Crystalline and amorphous dispersions have been the focus of academic and industrial research due to their potential role in formulating poorly water-soluble drugs. This review looks at the progress made starting with crystalline carriers in the form of eutectics moving towards more complex crystalline mixtures. It also covers using glassy polymers to maintain the drug as amorphous exhibiting higher energy and entropy. However, the amorphous form tends to recrystallize on storage, which limits the benefits of this approach. Specific interactions between the drug and the polymer may retard this spontaneous conversion of the amorphous drug. Some studies have shown that it is possible to maintain the drug in the amorphous form for extended periods of time. For the drug and the polymer to form a stable mixture they have to be miscible on a molecular basis. Another form of solid dispersions is pharmaceutical co-crystals, for which research has focused on understanding the chemistry, crystal engineering and physico-chemical properties. USFDA has issued a guidance in April 2013 suggesting that the co-crystals as a pharmaceutical product may be a reality; but just not yet! While some of the research is still oriented towards application of these carriers, understanding the mechanism by which drug-carrier miscibility occurs is also covered. Within this context is the use of thermodynamic models such as Flory-Huggins model with some examples of studies used to predict miscibility.

Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles

“…The stabilizers adsorbed on the nanoparticles surface during the FNP process can decrease particle size significantly by reducing the interfacial energy at solid-liquid interface and increasing the nucleation rate 40 , 64 . On the other hand, it also can provide a long-term stability by limiting the Ostwald ripening 65 , crystal form transformation 66 , 67 and nanoparticle agglomeration 68 , 69 .…”

“…Because of the solubility of the metastable crystal is higher than that of the stable crystal, the difference of the solubility of the different crystal forms is the driving force of the crystalline transformation. Therefore, many studiers used suitable excipients 66 , 67 and combined with freeze-drying or spray-drying by removing water medium to stabilize the drug nanoparticles as amorphous 61 , 62 , 63 , 97 , 98 , 104 , 105 , 106 , 108 , 112 .…”

Pulmonary Drug Delivery of Antimicrobials and Anticancer Drugs Using Solid Dispersions

“…Most solid APIs exist in a crystalline state held together by strong intermolecular bonds, and therefore, display good stability profiles ( Figure 3 ). However, the crystalline state often shows poor solubility, due to the high energy required to break the crystalline lattice which creates a major problem for developing new APIs [ 112 , 113 ]. There has been much interest in the process of ‘drug amorphisation’, to address poor solubility, which involves the conversion from a crystalline state to an amorphous solid state.…”

Preparation and Physiochemical Analysis of Novel Ciprofloxacin / Dicarboxylic Acid Salts

“…Aqueous solubility of active pharmaceutical ingredients (APIs) can be improved through the discovery of new solid forms. Common examples of different solid forms used are salts, polymorphs, amorphous and coamorphous forms, cocrystals, solvates and hydrates; these are the subject of several extensive reviews and studies [1][2][3][4][5][6][7] . In each of these cases, the same API can exhibit different physiochemical properties without change to the chemical structure [8][9][10] .…”