4 research outputs found
Formation of Protein and Protein–Gold Nanoparticle Stabilized Microbubbles by Pressurized Gyration
A one-pot
single-step novel process has been developed to form
microbubbles up to 250 μm in diameter using a pressurized rotating
device. The microbubble diameter is shown to be a function of rotational
speed and working pressure of the processing system, and a modified
Rayleigh–Plesset equation has been derived to explain the bubble-forming
mechanism. A parametric plot is constructed to identify a rotating
speed and working pressure regime, which allows for continuous bubbling.
Bare protein (lysozyme) microbubbles generated in this way exhibit
a morphological change, resulting in microcapsules over a period of
time. Microbubbles prepared with gold nanoparticles at the bubble
surface showed greater stability over a time period and retained the
same morphology. The functionalization of microbubbles with gold nanoparticles
also rendered optical tunability and has promising applications in
imaging, biosensing, and diagnostics
Development and Characterization of Amorphous Nanofiber Drug Dispersions Prepared Using Pressurized Gyration
Nanofibrous
systems are attracting increasing interest as a means
of drug delivery, although a significant limitation to this approach
has been manufacture on a scale commensurate with dosage form production.
However, recent work has suggested that nanofibers may be successfully
manufactured on a suitable scale using the novel process of pressurized
gyration (PG). In this study, we explore the potential of PG as a
novel means of generating amorphous solid dispersions of poorly water-soluble
drugs with enhanced dissolution performance. We examine the effect
of increasing drug loading on fiber properties including size, surface
characteristics, and the physical state of both components. Dispersions
of ibuprofen in poly(vinylpyrrolidone) (PVP) were prepared (up to
50% w/w loading) and characterized using a range of imaging, thermal,
diffraction, and spectroscopic techniques, while the release profiles
were studied using sink and non-sink (pH 1.0) conditions. The drug
was found to be dispersed on a molecular basis within the fibers;
attenuated total reflection FTIR indicated evidence for a direct interaction
between the drug and polymer at lower drug loading by the identification
of a strong single band in the carbonyl region and amide region of
ibuprofen and PVP respectively. Dissolution studies under sink conditions
indicated a substantial increase in release rate, while non-sink studies
showed evidence for supersaturation. It is concluded that PG presents
a viable method for the production of drug-loaded nanofibers for oral
administration with enhanced <i>in vitro</i> dissolution
rate enhancement
Identification and Characterization of Stoichiometric and Nonstoichiometric Hydrate Forms of Paroxetine HCl: Reversible Changes in Crystal Dimensions as a Function of Water Absorption
Paroxetine hydrochloride (HCl) is an antidepressant drug,
reported to exist in the anhydrous form (form II) and as a stable
hemihydrate (form I). In this study, we investigate the hydration
behavior of paroxetine HCl form II with a view to understanding both
the nature of the interaction with water and the interchange between
forms II and I as a function of both temperature and water content.
In particular, we present new evidence for both the structure and
the interconversion process to be more complex than previously recognized.
A combination of characterization techniques was used, including thermal
(differential scanning calorimetry (DSC) and thermogravimetric analysis
(TGA)), spectroscopic (attenuated total reflectance Fourier transform
infrared spectroscopy (ATR-FTIR)), dynamic vapor sorption (DVS) and
X-ray powder diffraction (XRPD) with variable humidity, along with
computational molecular modeling of the crystal structures. The total
amount of water present in form II was surprisingly high (3.8% w/w,
0.8 mol of water/mol of drug), with conversion to the hemihydrate
noted on heating in hermetically sealed DSC pans. XRPD, supported
by ATR-FTIR and DVS, indicated changes in the unit cell dimensions
as a function of water content, with clear evidence for reversible
expansion and contraction as a function of relative humidity (RH).
Based on these data, we suggest that paroxetine HCl form II is not
an anhydrate but rather a nonstoichiometric hydrate. However, no continuous
channels are present and, according to molecular modeling simulation,
the water is moderately strongly bonded to the crystal, which is in
itself an uncommon feature when referring to nonstoichiometric hydrates.
Overall, therefore, we suggest that the anhydrous form of paroxetine
HCl is not only a nonstoichiometric hydrate but also one that shows
highly unusual characteristics in terms of gradual unit cell expansion
and contraction despite the absence of continuous channels. These
structural features in turn influence the tendency of this drug to
convert to the more stable hemihydrate. The study has implications
for the recognition and understanding of the behavior of pharmaceutical
nonstoichiometric hydrates
Generation and Characterization of Standardized Forms of Trehalose Dihydrate and Their Associated Solid-State Behavior
Trehalose
dihydrate is a nonreducing disaccharide which has generated
great interest in the food and pharmaceutical industries. However,
it is well recognized that considerable batch to batch variation exists
for supposedly identical samples, particularly in terms of the thermal
response. In this investigation, two standardized forms of trehalose
dihydrate were generated using two distinct crystallization pathways.
The two batches were characterized using scanning electron microscopy,
X-ray powder diffraction, and FTIR. The thermal responses of the two
forms were then studied using modulated temperature differential scanning
calorimetry (MTDSC) and thermogravimetric analysis (TGA). In particular,
we describe the technique of quasi-isothermal MTDSC as a means of
studying the change in equilibrium heat capacity as a function of
temperature. Finally, variable temperature FTIR was utilized to assess
the change in bonding configuration as a function of temperature.
SEM revealed significant differences in the continuity and grain structure
of the two batches. The TGA, MTDSC, and quasi-isothermal MTDSC studies
all indicated significant differences in the thermal response and
water loss profile. This was confirmed using variable temperature
FTIR which indicated differences in bond reconfiguration as a function
of temperature. We ascribe these differences to variations in the
route by which water may leave the structure, possibly associated
with grain size. The study has therefore demonstrated that chemically
identical dihydrate forms may show significant differences in thermal
response. We believe that this may assist in interpreting and hence
controlling interbatch variation for this material