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Melt Granulation
Published in Dilip M. Parikh, Handbook of Pharmaceutical Granulation Technology, 2021
Shana Van de Steene, Valérie Vanhoorne, Chris Vervaet, Thomas De Beer
In addition to the drug release profile, the miscibility of the API and the binder must be taken into account. If the formulation is miscible, interactions like hydrogen bonding can take place between API and excipients. These can influence the glass transition temperature of the binder due to a plasticizing effect. Furthermore, it can affect the rheological properties of the binder or inhibit the distribution of the binder over the powder particles. In contrast, in an immiscible system, the binder can easily distribute over the powder particles once the binder is molten. The miscibility of all ingredients can be predicted by calculating the three-dimensional Hansen solubility parameters or it can be determined via differential scanning calorimetry (DSC) or spectroscopic analysis [9,64,70–73].
Physicochemical properties of respiratory particles and formulations
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
In addition to the optimized aerodynamic diameter combined with a larger geometric diameter, spray-dried particles often exhibit higher particle rugosity (surface asperities), which is also advantageous for reducing the aggregates strength. All of these factors lead to the possibility of high emitted dose, low device retention, and high FPF which may be between 65% and 95% (15,16). Here the effect of surface morphology on the aggregate packing can be more important than the reduction of interparticulate forces: the asperities and low particle density both lead to formation of loose aggregates desired for better fluidization and dispersion in DPIs. On the other hand, reduced flowability of such powders compared with the engineered blends has necessitated the use of more advanced filling machines (8,16). Another very important approach is the incorporation of force-control agents into the particle shell, which can be applied to both low-density particles and particles with relatively high density (ρp > 1 g/cm3) (35). Phosphatidylcholines such as distearoyl phosphatidylcholine (DSPC) and dipalmitoyl phosphatidylcholine (DPPC) can serve this purpose, with the very significant advantage of being endogenous surfactants present in the lungs. In addition, DPPC has been shown to enhance the permeation (absorption) of some active ingredients (15). DSPC is approved as a shell-forming excipient in TOBI Podhaler with a nominal daily dose of more than 50 mg (8). These surfactant molecules tend to accumulate on particle surfaces during spray drying, thus enhancing their surface modification effect. Another extensively studied group of compounds include hydrophobic amino acids, from which leucine has shown an exceptional dispersion enhancing effect for a number of spray-dried pulmonary formulations (15,35). For instance, in the case of disodium cromoglycate (DSCG) (35), the relatively strong cohesion characteristic of the pure drug resulted in a strong dependence of FPF on the inhalers type and the airflow rate, but leucine-containing powders exhibited a significant increase in FPF and a reduction of FPF dependence on the flow rate and inhaler type. It was proposed that this effect can be correlated with the different polarity of intermolecular interactions between DSCG and leucine at the particle surface, expressed by the difference in their component Hansen solubility parameters measured by IGC. In this work it was also suggested that higher segregation of leucine on the particle surfaces, even for dense particles, may lead to increased particle rugosity.
Influence of process temperature and residence time on the manufacturing of amorphous solid dispersions in hot melt extrusion
Published in Pharmaceutical Development and Technology, 2022
Tobias Gottschalk, B. Grönniger, E. Ludwig, F. Wolbert, T. Feuerbach, G. Sadowski, M. Thommes
In order to quantify the maximum amount of drug soluble in the polymer in the equilibrium state at a specific temperature, the solubility temperature needs to be considered. For a specific drug weight fraction, the solubility temperature gives the minimum required temperature to dissolve the drug in the polymer. For the determination of the solubility temperature of drugs, various theoretical approaches can be applied with different experimental efforts. Ruether and Sadowski (2009) divided these approaches into two groups depending on the solubility-related parameters. An empirical approach is correlating the solubility to physical properties or to different group contributions of a molecule. Here, using Hansen solubility parameters is a widely known approach (Hansen 1967), which was further developed in numerous works (Pearce 1977; Just et al. 2013). The other type of approaches is calculating the solubility from the chemical potential of the drug. A representative in this group is the perturbed-chain statistical associating fluid theory (PC-SAFT) (Gross and Sadowski 2001). The advantage of the second type of approach is the small amount of required experiments in comparison to the first group of approaches (Ruether and Sadowski 2009).
Ginsenoside CK-loaded self-nanomicellizing solid dispersion with enhanced solubility and oral bioavailability
Published in Pharmaceutical Development and Technology, 2020
Liyan Zhao, Lei Wang, Liping Chang, Yunlong Hou, Cong Wei, Yiling Wu
The drug-polymer miscibility is evaluated by Hansen solubility parameters (δ) of the drug and the polymer. Here, for Δδ < 7.0 MPa1/2, the miscibility of drug-polymer is likely to occur, whereas for Δδ > 7.0 MPa1/2, it is not (Kaljević et al. 2017). The δ values of CK and polymers were calculated using the atomic group contribution method and HSPiP Software according to Equations (1) to (4) (Stefanis and Panayiotou 2012): Ci is the contribution of molecular structure in the first-order group, Dj is the contribution of the second-order group, Ni is the number of Ci appears, Mj is the number of Dj, and δd, δp, and δh are the dispersive, electrostatic-polar, and hydrogen bonding forces, respectively. In this study, the solubility parameter of CK was 16.8 MPa1/2. The solubility parameters were 19.4 MPa1/2 for soluplus (Kaljević et al. 2017), 22.9 MPa1/2 for PEG (Barmpalexis et al. 2018), 26.55 MPa1/2 for PVPK30 and 21.31 MPa1/2 for PVA64 (Guan et al. 2019). All the Δδ values of polymers were below 7 indicating good compatibility with CK except PVPK30. The selected polymers were in the following order: soluplus > PVPVA64 > PVPK30 > PEG and soluplus presented the best compatibility.
Hansen solubility parameters (HSP) for prescreening formulation of solid lipid nanoparticles (SLN): in vitro testing of curcumin-loaded SLN in MCF-7 and BT-474 cell lines
Published in Pharmaceutical Development and Technology, 2018
Slavomira Doktorovova, Eliana B. Souto, Amélia M. Silva
Theoretical partial and total Hansen solubility parameters (δ, HSP) (Hansen, 2007) were calculated in agreement with the previously reported group contribution method by van Krevelen and Hoftyzer (van Krevelen and te Nijenhuis 2009). Partial δ values were calculated considering that: Fd, Fp, Eh represent the group contribution to dispersion forces, polar forces and hydrogen bond energy, respectively. Vm represents molar volume that can also be estimated from group contributions. Fd, Fp and Eh values published by van Krevelen (van Krevelen and te Nijenhuis 2009) and Equations (1–3) were used for the calculations. Total solubility parameters (δt) were calculated as follows: