Food selection and effect of home preparation procedure for antibiotic food mixtures on homogeneity, stability, and dissolution.

Amoxicillin, doxycycline, and clindamycin are among the commonly used antibiotics to treat bacterial infections. However, dosage forms of antibiotics for pediatric patients may not be as readily available as the formulations for adult patients. As such, it is anticipated that during a public health emergency, special instruction may need to be provided on home preparation and administration procedures to dose pediatric patients using available stockpiles of oral tablet and capsule dosage forms. Mixing crushed tablets or capsule contents with soft- or liquid- foods is one of the most common home preparation procedures. To gain knowledge for safe and effective use of prepared drug product instead of the intended intact dosage form, the impact of manipulation of the dosage form was studied. Capsule opening, capsule content assay and uniformity, dissolution, homogeneity, and stability studies of drug mixed with various liquid and soft foods were carried out using intact capsules of amoxicillin, doxycycline, and clindamycin. Higher recovery of capsule contents was achieved when using hands or knives to open capsules compared to using scissors. The capsules of all three antibiotic products contained the labeled amount of active pharmaceutical ingredients (API). The peanut butter-drug mixtures failed both United States Pharmacopeia (USP) assay and dissolution criteria because the peanut butter significantly affected the solubility of the drugs, and hence it was omitted from further study. All drug-food mixtures of the three antibiotic products and 15 selected foods exhibited fast dissolution (e.g., >80 % in 60 min) in the tested medium, except for the amoxicillin-chocolate pudding mixture. Three household containers (cups, plates, and bowls) and four mixing times (0.5 min, 1 min, 2 min, and 5 min) were found to be suitable for preparation of homogeneous mixtures of the antibiotics and foods. For practical purposes, 1 to 2 min mixing time is sufficient to produce homogeneous mixtures. The results of this study provided product quality data on the interactions between the antibiotics and the foods and can potentially support future development of home preparation instructions of antibiotics for pediatric patients or patients with swallowing difficulties.

Long-term fretting corrosion performance of modular head-neck junctions with self-reinforced composite gaskets from PEEK and UHMWPE.

Soft gasket-like polymer films may provide multiple advantages in inhibiting fretting corrosion between metal-hard surfaces in total joint implants. Self-reinforced composites (SRC's) made from either poly(ether ether ketone), SRC-PEEK, or ultra high molecular weight polyethylene, SRC-PE, were fabricated and tested to investigate their ability to limit or prevent mechanically assisted corrosion in modular taper devices. Hot compaction was used to create nominally 100 µm thick unidirectional composite gaskets. These gaskets were placed on the trunnions of modular head-neck tapers and seated with 4000 N. One million cycle potentiostatic fretting corrosion tests (3000 N, R = 0.1, 15 Hz, -0.05 V) were employed to assess the ability of these SRCs to reduce or prevent fretting corrosion damage in the modular taper junction. Fretting currents and head-neck micromotion were evaluated. The results of testing, along with pull-off tests and optical and scanning electron microscopic analysis showed that SRC gaskets reduced or eliminated fretting corrosion currents, with the SRC-PEEK performing better than the SRC-PE. Fretting currents were low for SRC's compared to metal-metal tapers. No wear through of the gaskets was noted and minimal wear damage was seen in the SRC-PEEK gaskets. SRC-PE gaskets demonstrated greater deformation and damage compared to the SRC-PEEK gaskets. Pull-off loads for the SRC-PEEK were higher than SRC-PE and not statistically different than the control metal-metal junctions. There was evidence of fatigue cracks forming at the high stress concentration junctions for the SRC-PEEK at the thread form corners of the trunnion, but no loss of integrity was observed. SRC-PEEK gaskets show promise as a method to eliminate modular taper fretting corrosion.

Sub-nano to nanometer wear and tribocorrosion of titanium oxide-metal surfaces by in situ atomic force microscopy.

Wear and tribocorrosion of passive oxide film covered metals have been studied at the micro and macroscopic scales. Recent advances in nanotechnology have contributed to breakthroughs in understanding of fundamental friction and wear mechanisms of atomically thin 2D materials at the nanoscale. However, for metals and materials without ultra-flat surfaces, a gap in knowledge exists at or below a few nanometers, which is too small for continuum mechanics theories and experiments including conventional atomic force microscopy (AFM) methods, due to resolution limits arising from surface roughness. Here, we report the near-atomic-scale wear of titanium in air and physiological solution from a single atomic layer to beyond the full oxide thickness using an AFM-based tribology method. Sub-nano to nanometer wear of titanium was revealed with different stages of contact pressure dependent wear regions identified as wear depth increased, featured by a transition from atomic wear (below 2.4 GPa) to elasto-plastic driven wear (above 3.6 GPa) at its oxide thickness (3.8 nm) in air. Higher stress was required to generate a similar wear penetration process in PBS compared to air. Tribocorrosion at this scale was grain orientation and voltage-dependent. Our study opens up a new method to achieve reliable angstrom-level resolution wear quantification to advance the understanding of wear and tribocorrosion of metals at the nanoscale. STATEMENT OF SIGNIFICANCE: Experimental tests of wear for metallic biomaterials at the nanoscale are difficult because engineered metal surfacesare never perfectly atomically flat, limiting the resolution of precise wear measurements to a few nanometers scale or more. To systematically address this problem, we have introduced the AFM 'image-wear-image' tribology method and obtained quantitative stress dependent measurement of the near-atomic-scale wear of titanium surfaces in air and tribocorrosion in physiological solution from a single atomic layer to beyond the full oxide film thickness. This allowedto measure sub-nano scale wear by partial removal of oxide. Nanoscale wear has been found to be grain orientation-dependent above the 'atomic scale' wear region. The nano-tribocorrosion of CP-Ti across scales and voltage effects on oxides in physiological solution was studied. Our study opens up a new method for future studies to advance the understanding of sub-nanoscale and nanoscale wear and tribocorrosion phenomenon as well as oxide growth mechanism of metallic biomaterials.

Micromechanical measurement of adhesion of dehydrating silicone hydrogel contact lenses to corneal tissue.

Adhesion properties, which can vary with multiple factors, of silicone hydrogel contact lenses are important to their performance and comfort in the eye. In this study, we developed and used a simple, representative testing system and method to study the adhesive interactions of different silicone contact lenses (balafilcon A and senofilcon A) on polished titanium alloy and porcine whole eye cornea under dehydrating conditions. Adhesive interactions for senofilcon A varied by hydration state for both corneal and titanium adhesion, starting low, rising to a maximum and falling with dehydration time and dehydration state. Balafilcon A showed a rise and fall against titanium, but retained a relatively constant adhesive interaction with corneal tissue over dehydration time. Senofilcon A reached the highest adhesion forces (400 mN) within 5 to 10 min of testing against cornea, then dropped with time after that. Johnson-Kendall-Roberts (JKR) theory was applied to determine the surface energy of the lenses, and work of adhesion (WOA) was also determined for both lenses. Similar trends as observed with the force-hydration curves were seen with surface energy and work of adhesion as well (peak surface energy of 8 N/m and work of adhesion of 80 µJ for senofilcon A). Video imaging of the adhesive interactions showed significant corneal deformation taking place during testing, and post-test analysis shows damage to the corneal tissue. This method could be used to assess pre-clinical performance of long-lasting contact lenses and the role of hydration state. STATEMENT OF SIGNIFICANCE: Adhesion properties of contact lenses play significant roles in their performance and comfort in the eye. Adhesion is influenced by polymer chemistry, counterface materials and hydration state of the contact lenses. However, no test method has been developed to directly study the adhesion properties between contact lenses and corneal tissue during the dehydration process. Our work aims to fill this gap by developing testing and analysis methods for evaluating the adhesive interactions in vitro between contact lenses of different chemistries and properties and different counter surfaces under dehydrating conditions over time. Our study shows that adhesive interactions of contact lenses are highly dependent on polymer type, surface treatment, counterface material and hydration state.

Analyzing ophthalmic suspension particle size distributions using laser diffraction: Placebo background subtraction method.

The current study demonstrated that the presence of excipients can interfere with the measurement of particle size distribution (PSD), a critical quality attribute of ophthalmic suspensions, by laser diffraction (LD) and that a placebo background subtraction approach can eliminate the impact of excipients on the PSD measurement. Commercially available loteprednol etabonate and brinzolamide ophthalmic suspensions were used as model suspensions. The impact of excipients in these formulations on the LD measurements was determined using a one-factor-at-a-time experimental design approach, using National Institute of Standards and Technology (NIST) traceable polystyrene particle size standards as references. Among the evaluated excipients, polymers containing polyacrylic acid were found to interfere with the PSD analysis by creating the LD signals correspond to particles ranging from a few micrometers to a hundred micrometers in size. As a result, the measured PSD of active pharmaceutical ingredient (API) particles in the formulation overlapped with or superimposed on the excipient PSD signal, leading to erroneous interpretation of the API particle size. Additionally, dispersion of brinzolamide particles in unsaturated solutions led to rapid dissolution of brinzolamide particles during the measurement, resulting in underestimation of the particle size range. Here, a placebo background subtraction approach was developed to eliminate the interference of the excipients. This newly developed LD method was also evaluated using orthogonal methods, including polarized light microscopy and scanning electron microscopy (SEM). The strategy used in this study to eliminate the interference of excipients may also be useful for other heterogeneous dispersions where excipient interference may be of concern.

Potential effect of epigenetic drugs in the treatment of multiple-site extramedullary plasmacytoma involving the respiratory system: a case report and review of the literature.

We report the case of a 23-year-old man with a medical history of idiopathic thrombocytopenic purpura (ITP) and newly diagnosed with the Epstein-Barr virus (EBV)-positive multiple-site extramedullary plasmacytoma (EMP), which involves the respiratory system. The patient was referred to our hospital because of progressive nasal congestion and nasal mass. Nasopharyngoscopy and bronchoscopy were performed. The biopsy pathological hematoxylin and eosin (HE) staining indicated plasma cell myeloma, and further immunohistochemistry CD99(+), CD79a(+), CD38(+), MUM-1(+), and Lambda(+) confirmed the diagnosis. The patient's bone marrow was normal, and hypercalcemia, renal insufficiency, anemia, evident bone lesions were not observed. Serum immunoglobulin quantification, serum protein electrophoresis, and blood and urine light chain quantification were all within the normal range. The serum immunofixation electrophoresis was negative, and the serum-free light chain was normal. These results could rule out multiple myeloma (MM) and prove to be EMP involving the nasal cavity, main bronchus, lung, and left hip. No desired effect was achieved after receiving PAD (bortezomib, adriamycin, and dexamethasone) and VRD (bortezomib, lenalidomide, and dexamethasone) treatments. Even if the tumor was remarkably relieved after receiving the 2-course CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen, secondary resistance to CHOP unfortunately occurred in this case. We attempted to apply epigenetic therapy in the treatment of refractory multiple EMP. Although no complete remission (CR) was achieved, the maximum standard uptake value (SUVmax) in tumor lesions was significantly lower than before, and the patient's symptoms significantly improved. The patient tolerated decitabine and chidamide. We speculated that epigenetic drugs have potential effect in the treatment of multiple-site EMP.

In vitro fretting crevice corrosion damage of CoCrMo alloys in phosphate buffered saline: Debris generation, chemistry and distribution.

Fretting crevice corrosion in modular tapers of total hip replacements has become a major concern in orthopedic medical devices. Solid and ionic debris arising from fretting crevice corrosion have been implicated in device failure and revision surgery. This study aims to use a 2D pin-on-disk fretting corrosion test system to visualize damage progression and debris generation during fretting corrosion of CoCrMo alloys in phosphate buffered saline (PBS). The results provide direct evidence of rapid debris generation during fretting corrosion (after only 12 min of testing). Debris was generated and either extruded from the contact region or impacted into adjacent crevice sites as long as fretting continued. After testing, the fretting region consisted of a damaged and plastically deformed contact region surrounded by a halo of fretting debris consisting entirely of oxides and phosphates within the crevice region. Evidence of pitting corrosion and grain boundary corrosion was observed. Solid debris consisted of chromium (Cr), phosphate (P) and oxygen (O). X-ray photoelectron spectroscopy analysis of the near-fretted metal surface area showed a thicker oxygen (O1s) containing film with the depth profile of O1s above 10% penetrating up to 5.75 nm while the O1s concentration on the unfretted area fell to below 10% after 1 nm depth. Ion concentration in the PBS, measured using inductively coupled mass spectrometry, showed cobalt (Co) ions were most prevalent (1.46 ppm) compared to chromium (Cr) (0.07 ppm) and molybdenum (Mo) (0.05 ppm) (p <0.05). All of these results are consistent with the analysis of in vivo modular taper corrosion processes. STATEMENT OF SIGNIFICANCE: CoCrMo alloys has been widely used as a metallic biomaterial for implant devices and can lose their durability and reliability due to wear, corrosion and tribocorrosion. Debris, as one of the major products of these reactions, is associated with implant device failure. In the first time, we developed a fretting corrosion testing system to visualize the debris generation process in real-time between CoCrMo alloy pin and disk samples. Debris was generated rapidly during fretting corrosion and some of the debris egressed from the crevice site while also accumulating within the crevice area as fretting continued. Our study opens a new method for future studies to advance understanding of debris generation processes during wear and tribocorrosion phenomenon.

A metallic biomaterial tribocorrosion model linking fretting mechanics, currents, and potentials: Model development and experimental comparison.

Mechanically assisted crevice corrosion may disrupt passive oxide films on medical alloys and lead to rapid repassivation reactions which generate corrosion currents and shifts in electrode potential due to the non-equilibrium nature of the reactions and the transient unbalancing of anodic and cathodic reactions. This study presents a theoretical approach to predict currents and voltages over time utilizing the concepts of heredity integrals, area-dependent surface impedance, contact mechanics and the high field physics of oxide repassivation. Two heredity integrals are presented relating, first, the sliding mechanics and oxide film repassivation physics to the current, and second, relating the electrode potential to the current using impedance concepts. Current-potential-time responses to controlled fretting conditions were measured across a fretting frequency from 0.2 to 10 Hz and compared to theoretical results. The coupled integrals were shown to predict the overall current-potential-time behavior for CoCrMo alloy surfaces under several controlled fretting corrosion conditions (loads, sliding speeds, etc.) with a high degree of similarity. These models can be adapted to numerical analyses of tribocorrosion to predict performance.

Fretting corrosion of Si3 N4 vs CoCrMo femoral heads on Ti-6Al-V trunnions.

Fretting corrosion at the head-neck taper junction was compared between silicon nitride (Si3 N4 ) and commercially available cobalt chrome (CoCrMo) femoral heads on titanium (Ti-6Al-4V) trunnions. An electrochemical setup was used to capture the fretting currents (characterized by oxide abrasion and repassivation) during cyclic loading. Onset load, pull-off force (disassembly load), short term and long term (1 million cycles) fretting currents were used to compare the fretting corrosion performance between the test group (Si3 N4 /Ti-6Al-4V) and the control group (CoCrMo/Ti-6Al-4V). Incremental cyclic fretting corrosion tests showed that the Si3 N4 /Ti-6Al-4V combination had statistically lower (P < .05) average fretting current of 0.189 µA (SD = 0.114 µA) compared to 0.685 µA (SD = 0.630 µA) for CoCrMo/Ti-6Al-4V for cyclic load of 3200 N. Similarly, for the one million cycle fretting corrosion tests, the Si3 N4 /Ti-6Al-4V couples had statistically lower (P < .05) average current (0.048 µA, SD = 0.025 µA) vs CoCrMo/Ti-6Al-4V couples (0.366 µA, SD = 0.143 µA). The Si3 N4 heads also had higher onset loads (P < .05) for fretting (vs CoCrMo, 2200 N vs 1740 N) indicating a difference in surface contact mechanics between the two groups. Scanning electron microscopy with energy dispersive spectroscopy confirmed material transfer from the trunnions to the heads for both groups tested, and from head to trunnion for the CoCrMo heads. Minimal Si3 N4 transfer was noted. The electrochemical, mechanical, and microscopic inspection data supported the hypothesis that Si3 N4 /Ti-6Al-4Vcombination had better fretting corrosion performance compared to CoCrMo/Ti-6Al-4V.

Effect of multipurpose care solutions upon physical dimensions of silicone hydrogel contact lenses.

Interactions between contact lens multipurpose solution (MPS) components and the contact lenses with which they are used are both lens and solution dependent. As such, lens dimensional changes may arise after cleaning and immersion cycling in different lens care solutions over different time courses. In this study, the dimensional stability of five planned-replacement silicone hydrogel lenses (lotrafilcon B, comfilcon A, senofilcon A, senofilcon C, and samfilcon A) over 30 cycles in three different MPSs (Biotrue, OPTI-FREE Express, and OPTI-FREE Puremoist) was evaluated. Measurements of diameter, sagittal depth, power, roundness, and center thickness were obtained prior to, during, and after 30 cycles of cleaning and storage. Diameters of all lenses increased when soaked in Express or Biotrue but held the International Standards Organization (ISO) tolerance over the full course of 30 disinfection cycles; however, the diameters of comfilcon A, senofilcon A, senofilcon C, and samfilcon A lenses soaked in Puremoist exceeded ISO tolerance after between 4 and 9 immersion cycles. In contrast, the diameter of lotrafilcon B held tolerance. Similarly, all lenses cycled in Express or Biotrue held tolerance for sagittal depth, while in Puremoist only lotrafilcon B held tolerance. All lenses became less round in all MPSs but held tolerance for both power and central thickness. Given the lack of reported clinical issues with Puremoist when used with lenses other than lotrafilcon B, we propose that it may be appropriate to revisit the ISO test methods and tolerances to determine if they are still applicable for silicone hydrogel lenses.

Fretting initiated crevice corrosion of 316LVM stainless steel in physiological phosphate buffered saline: Potential and cycles to initiation.

Mechanically assisted crevice corrosion (MACC) has been associated with implant failure in vivo and is a serious concern in numerous metallic implant systems. Stainless steel medical devices may be subjected to fretting and crevice corrosion in the human body as are titanium and CoCrMo alloys due to the presence of a passive oxide film on their surface. One mechanism of MACC that has not been clearly identified and studied is fretting-initiated crevice corrosion (FICC) of stainless steel where an initial fretting event can initiate a rapid propagating crevice corrosion process even when fretting has ceased. FICC pin-on-disk experiments were performed at varying potential conditions and duration of fretting to explore the role of potential and fretting duration on the initiation of crevice corrosion. Triggering of a propagating crevice corrosion reaction on stainless steel at 250 mV vs Ag/AgCl/KCl (saturated) in PBS solution required only 2 s (2 cycles at 1 Hz) of fretting. Crevice corrosion continued to propagate under a 1.8 mm diameter pin with only 100 µm of direct contact, dissolving in both the depth and width dimension away from the fretting contact while the currents rose from 0.2 µA to 15 µA within 5 min. Three different potential-dependent FICC regions were identified that included unstable crevice corrosion (50 mV and above), metastable crevice corrosion (-100 mV to 0 mV) and stable fretting corrosion (between -500 mV and -150 mV). Crevice corrosion can be induced by fretting at potentials as low as -100 mV. Below -100 mV, there was no FICC, but rather fretting corrosion stopped immediately after fretting ceased and returned to a stable baseline current. Metastable FICC was shown at potentials between -100 mV and 0 mV, when the crevice corrosion current gradually decreased over several seconds or longer after fretting ceased. Self-sustained, unstable crevice corrosion started at 50 mV, where prior to fretting the currents were low, and after just a few cycles of fretting the crevice current rose rapidly and continued to increase after fretting stopped. Increase of potential increased the susceptibility of stainless steel to FICC. Scanning electron microscopy and digital optical microscopy revealed pitting and crevice corrosion on samples at -100 mV and higher potentials, where FICC was developing. By removing the oxide film, fretting motion significantly facilitates the critical crevice solution development, lowering the critical crevice potential and decreasing the initiation time for crevice corrosion. These results indicate that fretting initiated crevice corrosion may affect the performance of stainless steel in vivo. STATEMENT OF SIGNIFICANCE: AISI 316L stainless steel has been widely used as a metallic biomaterial for orthopaedic, spinal, dental and cardiovascular implants. Crevice corrosion has been a serious concern for stainless steel implants. For the first time we demonstrated and systematically studied the process of fretting-initiated crevice corrosion (FICC) in 316L stainless steel in simulated physiological solution of phosphate buffered saline. By removing the oxide film, fretting motion significantly facilitates the critical crevice solution development, lowering the critical crevice potential and decreasing the initiation time for crevice corrosion. Our findings indicate fundamental differences between the FICC mechanism and conventional crevice corrosion theory, showing that fretting can play a significant role in the initiation of crevice corrosion of stainless steel.