Production of cocrystals in an excipient matrix by spray drying

Abstract

Spray drying is a well-established scale-up technique for the production of cocrystals. However, to the best of our knowledge, the effect of introducing a third component into the feed solution during the spray drying process has never been investigated. Cocrystal formation in the presence of a third component by a one-step spray drying process has the potential to reduce the number of unit operations which are required to produce a final pharmaceutical product (e.g. by eliminating blending with excipient). Sulfadimidine (SDM), a poorly water soluble active pharmaceutical ingredient (API), and 4-aminosalicylic acid (4ASA), a hydrophilic molecule, were used as model drug and coformer respectively to form cocrystals by spray drying in the presence of a third component (excipient). The solubility of the cocrystal in the excipient was measured using a thermal analysis approach. Trends in measured solubility were in agreement with those determined by calculated Hansen Solubility Parameter (HSP) values. The ratio of cocrystal components to excipient was altered and cocrystal formation at different weight ratios was assessed. Cocrystal integrity was preserved when the cocrystal components were immiscible with the excipient, based on the difference in Hansen Solubility Parameters (HSP). For immiscible systems (difference in HSP > 9.6 MPa), cocrystal formation occurred even when the proportion of excipient was high (90% w/w). When the excipient was partly miscible with the cocrystal components, cocrystal formation was observed post spray drying, but crystalline API and coformer were also recovered in the processed powder. An amorphous dispersion was formed when the excipient was miscible with the cocrystal components even when the proportion of excipient used as low (10% w/w excipient). For selected spray dried cocrystal-excipient systems an improvement in tableting characteristics was observed, relative to equivalent physical mixtures.

Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms

“…In order to investigate the diffusion kinetics of NDF from the solvent into the different filaments, the degree of miscibility between the drug and the solvent molecules and also between the solvent molecule and the filament were calculated. Several approaches, such as the Hansen Solubility theory, have been used in the past to estimate the degree of miscibility of different materials, for example, during co-crystal formation or amorphous solid dispersion development [21,22]. Typically, it is assumed that materials with similar cohesive energy density will be miscible with one another, and the total cohesive energy can be divided into the individual, so-called, Hansen Solubility Parameters (HSP): dispersion forces (δd), polar forces (δp) and hydrogen bonding forces (δh).…”

Optimising the in vitro and in vivo performance of oral cocrystal formulations via spray coating

“…The binder is necessary to ensure the appropriate deposition of the cocrystal onto the beads; however if the amount is too high, H-bonding interactions between the cocrystal components with the binder could occur and affect the integrity of the cocrystal, leading instead to an amorphous system. Predicting the miscibility of cocrystal components between themselves as well as with the carrier excipient using solubility parameters such as Hansen Solubility Parameters can guide the selection of potential coformers and binders prior to cocrystal screening [39][40][41].…”

Pulmonary Drug Delivery of Antimicrobials and Anticancer Drugs Using Solid Dispersions

“…Another route being investigated is the generation of cocrystals and seems to be a promising method of improving physicochemical properties if other methods are not suitable. For example, with the formation of salts, if the API is neutral, and therefore, does not contain an acidic or basic group that can be ionised, salts cannot be practically formed [ 162 ]. Cocrystallisation may also be seen as a more desirable method of physicochemical enhancement than others, for example, CASDs, due to enhanced physical and chemical stability [ 163 ].…”