Abstract:Crystallization
of active pharmaceutical ingredients (APIs) from
the supercooled liquid state is an important issue in determining
the stability of amorphous pharmaceutical dispersions. In the present
study, the isothermal crystallization from the supercooled liquid
state of the pharmaceutical compound nifedipine was investigated by
both rheological and differential scanning calorimetry (DSC) measurements,
and the crystallization kinetics was fitted to the Johnson–Mehl–Avrami
(JMA) equation. Both the crystalli… Show more
“…Figure a shows the F ( t ) curves calculated from our experimental nucleation and growth rates, J and u , for pure and surfactant-doped NIF at 343 K. For pure NIF, our calculated curve (black) agrees reasonably well with Cheng and Mckenna’s experimental curve (light blue) measured by DSC . Relative to pure NIF, surfactant-doped NIF is predicted to crystallize much faster, with the half time of crystallization, t 0.5 , shortened by approximately 30 times.…”
Amorphous
formulations, increasingly employed to deliver poorly
soluble drugs, generally contain surfactants to improve wetting and dissolution. These
surfactants are often liquids and can potentially increase the mobility
of the drug and reduce its stability, but little is known about this
effect. Here we investigate the effect of four common nonionic surfactants
(Tween 80, Span 80, Triton X-100, and Poloxamer 407) on the crystallization
of amorphous nifedipine (NIF). We find that the surfactants significantly
enhance the rates of crystal nucleation and growth even at low concentrations,
by up to 2 orders of magnitude at 10 wt %. The surfactants tested
show similar enhancement effects independent of their structural details
and hydrophilic–lipophilic balance (HLB), suggesting that surfactant
adsorption at solid/liquid interfaces does not play a major role in
crystal nucleation and growth. Importantly, the surfactants accelerate
crystal nucleation and growth by a similar factor. This result mirrors
the previous finding that a polymer dopant in a molecular glass-former
causes similar slowdown of nucleation and growth. These results indicate
that nucleation and growth in a deeply supercooled liquid are both
mobility-limited, and a dopant mainly functions as a mobility modifier
(enhancer or suppressor depending on the dopant). The common surfactants
tested are all mobility enhancers and destabilize the amorphous drug,
and this negative effect must be managed using stabilizers such as
polymers. The effect of surfactants on nucleation can be predicted
from the effect on crystal growth and the crystallization kinetics
of the pure system, using the same principle previously established
for drug–polymer systems. We show how the independently measured
nucleation and growth rates enable predictions of the overall crystallization
rates.
“…Figure a shows the F ( t ) curves calculated from our experimental nucleation and growth rates, J and u , for pure and surfactant-doped NIF at 343 K. For pure NIF, our calculated curve (black) agrees reasonably well with Cheng and Mckenna’s experimental curve (light blue) measured by DSC . Relative to pure NIF, surfactant-doped NIF is predicted to crystallize much faster, with the half time of crystallization, t 0.5 , shortened by approximately 30 times.…”
Amorphous
formulations, increasingly employed to deliver poorly
soluble drugs, generally contain surfactants to improve wetting and dissolution. These
surfactants are often liquids and can potentially increase the mobility
of the drug and reduce its stability, but little is known about this
effect. Here we investigate the effect of four common nonionic surfactants
(Tween 80, Span 80, Triton X-100, and Poloxamer 407) on the crystallization
of amorphous nifedipine (NIF). We find that the surfactants significantly
enhance the rates of crystal nucleation and growth even at low concentrations,
by up to 2 orders of magnitude at 10 wt %. The surfactants tested
show similar enhancement effects independent of their structural details
and hydrophilic–lipophilic balance (HLB), suggesting that surfactant
adsorption at solid/liquid interfaces does not play a major role in
crystal nucleation and growth. Importantly, the surfactants accelerate
crystal nucleation and growth by a similar factor. This result mirrors
the previous finding that a polymer dopant in a molecular glass-former
causes similar slowdown of nucleation and growth. These results indicate
that nucleation and growth in a deeply supercooled liquid are both
mobility-limited, and a dopant mainly functions as a mobility modifier
(enhancer or suppressor depending on the dopant). The common surfactants
tested are all mobility enhancers and destabilize the amorphous drug,
and this negative effect must be managed using stabilizers such as
polymers. The effect of surfactants on nucleation can be predicted
from the effect on crystal growth and the crystallization kinetics
of the pure system, using the same principle previously established
for drug–polymer systems. We show how the independently measured
nucleation and growth rates enable predictions of the overall crystallization
rates.
“…NIF was variously studied using dielectric spectroscopy 23,69,79 and recently also using shear mechanical measurements. 15 Analogous to Figure 7, we compare the measured dielectric spectra of NIF with those predicated on the basis of the shear mechanical data and find excellent agreement; see Figure 13.…”
Section: ■ Details Regarding Migrationmentioning
confidence: 55%
“…Not the least to check whether or not a correlation of Δε and λ –1 does exist, cf. Figure , we analyzed additional data of nonassociating glass-forming liquids using this approach. NIF was variously studied using dielectric spectroscopy ,, and recently also using shear mechanical measurements . Analogous to Figure , we compare the measured dielectric spectra of NIF with those predicated on the basis of the shear mechanical data and find excellent agreement; see Figure . 13 (a) Dielectric constant ε′ and (b) dielectric loss ε″ loss spectra (full symbols) of nifedipine calculated on the basis of the shear mechanical data from the modified GDB approach by means of eqs , , and using λ –1 = 3.3 GPa.…”
mentioning
confidence: 55%
“…One goal of the present work is to check these concepts for several drugs in detail, i.e., to start from dielectric spectroscopy and to try to predict rheological properties and vice versa. In this endeavor, one can rely on mechanical data available in the literature, e.g., for indomethacin (IMC), , nifedipine (NIF), and ibuprofen (IBU) . From a survey, it turned out that for a number of other drugs including acetaminophen (AMP), nicotine (NIC), and L-HCl frequency-dependent rheological data are apparently not available .…”
Section: Introductionmentioning
confidence: 99%
“…Figure 13. (a) Dielectric constant ε′ and (b) dielectric loss ε″ loss spectra (full symbols) of nifedipine calculated on the basis of the shear mechanical data15 from the modified GDB approach by means of eqs 13, 14a, and 14b using λ −1 = 3.3 GPa. The calculated results are shown as open symbols.…”
Acetaminophen, nicotine, and lidocaine hydrochloride were investigated in their deeply supercooled liquid states using oscillatory shear rheology. The mechanical spectra of these drugs are presented in modulus, compliance, as well as fluidity formats. Their frequency profiles can be described via models adapted from the field of charge transport. Inspired by the success of this approach, the Barton−Nakajima−Namikawa relation, best known from the same field, was also tested. When adapted to rheology, this approach interrelates static and dynamic characteristics of viscous flow and was found to work excellently. The temperature dependence of the characteristic shear frequencies was checked against the shoving model, which relates them to the temperature-dependent instantaneous shear modulus and acceptable agreement was found. Combined with shear mechanical literature data on ibuprofen and indomethacin, a modified version of the phenomenological model by Gemant, DiMarzio, and Bishop (GDB) was employed to successfully predict the shape and amplitude of the dielectric spectra for all studied liquids, except for lidocaine hydrochloride. For the latter, the modified GDB model is suggested to aid in mapping out the reorientational part of the dielectric response, while the experimental results are strongly superimposed by ionic conduction phenomena. The reverse transformation, the calculation of rheological spectra based on dielectric ones, is also successfully demonstrated. For the example of acetyl salicylic acid, it is shown how dielectric spectra can be used to even predict rheological ones. The limits of the central parameter governing these mutual transformations, the electroviscoelastic material constant, and indications for its correlation with the dielectric relaxation strength are discussed. For pharmaceuticals characterized by a strong dynamical decoupling of the electrical from the mechanical degrees of freedom, the modified GDB model is not expected to be applicable.
The known studies of heat treatment of copper slag are mainly directed to the recovery of metals from copper slag at the melting temperature. The conditions of increasing the strength of copper slag grains as a result of transition from amorphous to crystalline state during heating have not been studied. That is why the paper presents studies of microhardness and cutting properties of copper slag particles after heat treatment. Treatment regimes were assigned after calorimetric measurements of phase transition from amorphous to crystalline state of copper slag grains under isothermal conditions. It was found that for copper slag grains crystallization proceeds in two stages. The rst crystallization stage started at 762.6 ℃ (1035.75 K) and the second one at 795.1 ℃ (1068.25 K). Metallographic examination of microslides of copper slag grains after heat treatment at 800 ℃ showed that the HV microhardness value increased 1.5 times. It was found that the use of heat-treated copper slag grains for water jet cutting resulted in an accurate cut and smooth surface compared to the original abrasive. It has been revealed that heat treatment of amorphous copper slag contributed to the appearance of crystallites of sillimanite, pyrope, hematite, and zinc ferrite.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
