Crystallization tendency of APIs possessing different thermal and glass related properties in amorphous solid dispersions

Drug crystal growth in ternary amorphous solid dispersions: Effect of surfactants and polymeric matrix-carriers

“…1 a showed a melting endotherm at T melt,ons = 251.42 °C (ΔH f of 118.56 J/g) corresponding to the co-melting of APT form I and II crystals, while upon reheating the API showed a single T g at 84.10 °C, followed by a recrystallization exotherm at 145.83 °C and a melting endotherm at T melt,ons of 237.38 °C. Based on this thermal profile the API can be considered as a non-stable glass former (this is in agreement with previously published results ( Kapourani et al, 2020b )). In the case of HPC-SL a broad endothermic peak was recorded during the 1st DSC heating scan, corresponding to the presence of residual moisture, while 2nd DSC heating scans for PVP and SOL showed a T g at 138.15 °C and 65.26 °C, respectively.…”

“…However, although APT-PVP melts seemed to be less favorable, the use of PVP, as compared to the rest binary components, lead to a higher single ASD T g value, indicating enhanced anti-plasticizing effect on the API. In addition, taking into consideration that the glass transition temperature of APT is 84.10 °C (a similar T g was also reported previously ( Kapourani et al, 2020b )), both surfactants (i.e., P407 and TPGS) showed a significant plasticizing ability. Moreover, based on the obtained DSC thermograms it should be noted that no API melting endotherms were recorded upon samples' reheating (i.e., 2nd DSC heating runs), indicating that the API was probably amorphously dispersed within all binary systems.…”

“…4 a illustrates the crystal growth rate of the API in the absence of any additive, as well as in the presence of a single polymeric carrier or a surfactant (at a ratio of 90/10 w /w APT to carrier/surfactant). It is noteworthy that, according to the previously discussed DSC results, APT may be considered as a non-stable glass former (following Baird et al classification system ( Baird et al, 2010 )) and hence, it is expected that the API is probably forming quite unstable amorphous glasses ( Kapourani et al, 2020b ). This assumption was confirmed from the obtained results, whereas the seeds of the crystalline API lead effortlessly to the nucleation and, subsequently, the crystal growth of the API in all experiments.…”

“…In this context, the present study is attempting to gain a further insight into the field, by extending the work of other research groups in regard to surfactant-based ternary ASDs characterization. For this purpose, ternary ASDs were prepared via melt mixing approach, using aprepitant (APT, an antiemetic agent having P/neurokinin 1 (NK1) receptors antagonist properties ( Barmpalexis et al, 2018a )) as a poor water soluble model drug, along with three commonly used polymeric matrix-carriers (namely, hydroxypropyl cellulose, HPC-SL, povidone, PVP, and polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer, Soluplus®) ( Barmpalexis et al, 2018b ; Barmpalexis et al, 2019 ; Ben Osman et al, 2018 ; Kapourani et al, 2020b ) and two widely used pharmaceutical surfactants (i.e., d-alpha tocopheryl polyethylene glycol 1000 succinate, TPGS, and poly(ethylene glycol)- block -poly(propylene glycol)- block -poly(ethylene glycol), Poloxamer 407). The prepared systems were evaluated in terms of API's crystal growth rate, water-induced nucleation induction time, amorphous suspension stability and molecular interactions both experimentally and theoretically (via molecular dynamics, MD, simulations).…”

Preparation and Characterization of Solid Dispersions Composed of Curcumin, Hydroxypropyl Cellulose and/or Sodium Dodecyl Sulfate by Grinding with Vibrational Ball Milling

“…Amorphous substances can be classified into two categories: molecularly pure drugs and solid dispersions (SDs), where the active pharmaceutical ingredient (API) is dispersed within a carrier(s). Vo et al have demonstrated that SDs can be categorized into four distinct subcategories [10]: (1) SDs that use a crystalline carrier, such as urea [11][12][13] or sugar [11]; (2) SDs that use a polymeric carrier, such as povidone [14], polyethylene glycol [15], hydroxypropyl cellulose [16] or cyclodextrin [17][18][19][20][21]; (3) SDs that use a carrier with surface activity, such as surfactant(s) or a mixture of polymers and surfactants [22]; and (4) controlled release SDs or SDs that use swellable/water insoluble polymers, such as Eudragit ® [23] and Carbopol ® [23].…”