Insight into polymorphism and dynamics of aripiprazole

Abstract

Phase sequence and molecular dynamics (molecular relaxation processes) of aripiprazole were studied by X-ray diffraction (XRD), differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and broadband dielectric spectroscopy (BDS). Polymorphism...

Mesoporous Matrices as a Promising New Generation of Carriers for Multipolymorphic Active Pharmaceutical Ingredient Aripiprazole

“…Our results obtained for the quenched APZ are in good agreement with DSC data published for this API by Knapik-Kowalczuk et al, 53 which showed similar values of T g (306 K), T c (363 K), and T m (∼406 and ∼412 K). In addition, nearly the same melting temperatures (T m = 405.7 and 411.4 K, assigned, respectively, to the IV and III polymorphs of APZ) were determined from calorimetric measurements carried out by Osiecka-Drewniak et al 16 DSC curves collected for APZ infiltrated into three types of templates differ from those measured for the quenched (bulk) sample since they revealed the presence of the two well-visible glass transition events located below and above T g of the bulk API (see Figure 1(c,d)). According to the "two-layer"( or "core-shell") model, 54,55 this phenomenon, known as a "double glass transition" (DGT), reflects the presence of two groups of molecules with different mobility: (i) "interfacial", interacting directly with the inner surface of the pore wall and characterized by a higher T g (so-called T g , interfacial ), as well as (ii) "core", located in the middle of nanochannels, which are characterized by bulk-like mobility and lower T g (assigned as T g,core ).…”

“…Our results obtained for the quenched APZ are in good agreement with DSC data published for this API by Knapik-Kowalczuk et al, 53 which showed similar values of T g (306 K), T c (363 K), and T m (∼406 and ∼412 K). In addition, nearly the same melting temperatures ( T m = 405.7 and 411.4 K, assigned, respectively, to the IV and III polymorphs of APZ) were determined from calorimetric measurements carried out by Osiecka-Drewniak et al 16 …”

“…The selection of the most appropriate method depends on physiological factors (site of action, administration route, pH of body fluids) as well as the physicochemical characteristics of a given API, e.g., its chemical structure, susceptibility to thermal degradation, reactivity, or tendency to form various polymorphic forms. The last phenomenon is very common among many pharmaceuticals, e.g., paracetamol (acetaminophen), ritonavir, some local anesthetic compounds (lidocaine, procaine, benzocaine), statins, alendronic acid, rifaximin, or aripiprazole. , In light of current knowledge, different polymorphic forms of the same chemical compound may vary in their physicochemical properties, such as melting and sublimation temperatures, density, hardness, vapor pressure, refractive index, color, crystal shape, stability, hygroscopicity, reactivity, mechanical properties, solubility, as well as heat and rate of dissolution, which affect the bioavailability, and effectiveness of formulation procedures like the tableting . In this context, APIs’ polymorphism can have either positive or negative implications.…”

“…The last phenomenon is very common among many pharmaceuticals, e.g., paracetamol (acetaminophen), 9 ritonavir, 10 some local anesthetic compounds (lidocaine, procaine, benzocaine), 11 statins, 12 alendronic acid, 13 rifaximin, 14 or aripiprazole. 15 , 16 In light of current knowledge, different polymorphic forms of the same chemical compound may vary in their physicochemical properties, such as melting and sublimation temperatures, density, hardness, vapor pressure, refractive index, color, crystal shape, stability, hygroscopicity, reactivity, mechanical properties, solubility, as well as heat and rate of dissolution, which affect the bioavailability, and effectiveness of formulation procedures like the tableting. 17 In this context, APIs’ polymorphism can have either positive or negative implications.…”