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