The Study of the Influence of Formulation and Process Variables on the properties of Simvastatin-Phospholipid Complex

Objectives: The aim of the present study was to examine the influence of the formulation and process variables on the entrapment efficiency of simvastatin-phospholipid complex (SPC), prepared with a goal of improving the solubility and permeability of simvastatin. Method: The SPC was prepared using a solvent evaporation method. The influence of formulation and process variables on simvastatin entrapment was assessed using a central composite design. An additional SPC was prepared using the optimized variables from the developed quadratic model. This formulation was characterized for its physical-chemical properties. The functional attributes of the optimized SPC formulation were analyzed by apparent aqueous solubility analysis, in-vitro dissolution studies, dissolution efficiency analysis, and ex-vivo permeability studies. Results: The factors studied were found to significantly influence on the entrapment efficiency. The developed model was validated using the optimized levels of formulation and process variables. The physical-chemical characterization confirmed a formation of the complex. The optimized SPC demonstrated over 25-fold higher aqueous solubility of simvastatin, compared to that of pure simvastatin. The optimized SPC exhibited a significantly higher rate and extent of simvastatin dissolution (\u3e98%), compared to that of pure simvastatin (∼16%). The calculated dissolution efficiency was also found to be significantly higher for the SPC (∼54 %), compared to that of pure simvastatin (∼8%). Finally, the optimized SPC exhibited a significantly higher simvastatin permeability (\u3e78%), compared to that of pure simvastatin (∼11%). Implications: The present study shows that simvastatin-phospholipid complex can be a promising strategy for improving the delivery of simvastatin, and similar drugs with low aqueous solubility

Multi-Frequency Electrocochleography and Electrode Scan to Identify Electrode Insertion Trauma during Cochlear Implantation

Intraoperative electrocochleography (ECOG) is performed using a single low-frequency acoustic stimulus (e.g., 500 Hz) to monitor cochlear microphonics (CM) during cochlear implant (CI) electrode insertion. A decrease in CM amplitude is commonly associated with cochlear trauma and is used to guide electrode placement. However, advancement of the recording electrode beyond the sites of CM generation can also lead to a decrease in CM amplitude and is sometimes interpreted as cochlear trauma, resulting in unnecessary electrode manipulation and increased risk of cochlear trauma during CI electrode placement. In the present study, multi-frequency ECOG was used to monitor CM during CI electrode placement. The intraoperative CM tracings were compared with electrode scan measurements, where CM was measured for each of the intracochlear electrodes. Comparison between the peak CM amplitude measured during electrode placement and electrode scan measurements was used to differentiate between different mechanisms for decrease in CM amplitude during CI electrode insertion. Analysis of the data shows that both multi-frequency electrocochleography and electrode scan could potentially be used to differentiate between different mechanisms for decreasing CM amplitude and providing appropriate feedback to the surgeon during CI electrode placement

Design and evaluation of a cochlear implant strategy based on a "Phantom" channel.

Unbalanced bipolar stimulation, delivered using charge balanced pulses, was used to produce "Phantom stimulation", stimulation beyond the most apical contact of a cochlear implant's electrode array. The Phantom channel was allocated audio frequencies below 300 Hz in a speech coding strategy, conveying energy some two octaves lower than the clinical strategy and hence delivering the fundamental frequency of speech and of many musical tones. A group of 12 Advanced Bionics cochlear implant recipients took part in a chronic study investigating the fitting of the Phantom strategy and speech and music perception when using Phantom. The evaluation of speech in noise was performed immediately after fitting Phantom for the first time (Session 1) and after one month of take-home experience (Session 2). A repeated measures of analysis of variance (ANOVA) within factors strategy (Clinical, Phantom) and interaction time (Session 1, Session 2) revealed a significant effect for the interaction time and strategy. Phantom obtained a significant improvement in speech intelligibility after one month of use. Furthermore, a trend towards a better performance with Phantom (48%) with respect to F120 (37%) after 1 month of use failed to reach significance after type 1 error correction. Questionnaire results show a preference for Phantom when listening to music, likely driven by an improved balance between high and low frequencies

Assessment of Pediatric Middle Ear Effusions With Wideband Tympanometry.

OBJECTIVE: To determine if wideband tympanometry (WBT) can differentiate types of middle ear effusion (MEE): serous, mucoid, and purulent. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary care children\u27s hospital. METHODS: Children who met American Academy of Otolaryngology-Head and Neck Surgery\u27s guidelines for ventilation tube insertion had WBT after anesthesia induction but before tympanotomy. MEE was categorized into 1 of 4 comparison groups: serous effusion, mucoid effusion, purulent effusion, or no effusion. WBT measurements were averaged to 16 one-third octave frequency bands, and comparison of the absorbance patterns for each MEE type was performed through a linear mixed effects model. RESULTS: A total of 118 children (211 ears) were included: 47 females (39.8%) and 71 males (60.2%). The mean age was 2.73 years (95% CI, 2.25-3.22); mean weight, 14.35 kg (95% CI, 12.85-15.85); and mean CONCLUSIONS: WBT has potential use to differentiate types of MEE and should be studied further as a tool for investigating how the natural history and management of serous and mucoid effusions may differ

Initial Experiences with the Envoy Acclaim^® Fully Implanted Cochlear Implant

Introduction: Cochlear implantation has become the standard of care for the treatment of moderate-to-profound bilateral sensorineural hearing loss. However, current technologies, all of which rely on an external sound processor, have intrinsic limitations that prevent certain activities and diagnostics, thus hampering full integration into a patient’s lifestyle. The Envoy Medical (White Bear Lake, MN, USA) Acclaim® fully implanted cochlear implant is a new device currently undergoing testing that has been designed to alleviate many of the current constraints by housing all components within the patient, thus allowing for near-constant use in many environments that are not conducive to a traditional cochlear implant. Methods: As part of an Early Feasibility Study, three adult implant candidates were implanted with the Acclaim® cochlear implant. Surgical video and photography were taken, and initial observations were recorded. Implantation with the Acclaim® device is largely similar to a traditional cochlear implant, with modifications to allow room for the implanted sensor as well as the implantation of a battery in the subcutaneous tissues of the chest. Results: This study demonstrates a step-by-step overview of implanting the Acclaim® and discusses initial insight and experiences with the first three implantations with this new device. Conclusions: All three surgeries proceeded without complication, and at activation, all three patients were hearing through their devices. Surgery is more technically challenging compared to a standard cochlear implant, but the skills needed can all be mastered by a dedicated otologic surgeon

Results for the HSM sentence test during the second session.

<p>No significant difference was observed after Bonferroni correction (paired t-test p = 0.034).</p

Results for the question about the “overall impression” of music.

<p>The Phantom strategy was rated to sound significantly better than F120 (wilcoxon signed rank test p = 0.037).</p

Subject demographics.

<p>Subject demographics.</p

Schematic illustration of the Phantom effect for <i>σ</i> = 0 (a) and <i>σ</i> = 0.625 (b) on pitch perception.

<p>The electrical field is simulated using triangular functions and assuming linear superposition of the electrical field produced by each electrode. The center of masses of the electrical field is assumed to be related to the pitch elicited by the stimulation. Using Phantom stimulation it is possible to push the electrical field away from the most apical electrode.</p

Stimulation pattern for one cycle of Phantom strategy stimulation.

<p>CSR is the Channel Stimulation Rate for one electrode. In the Phantom strategy, the electrode contacts 1 and 2 are stimulated simultaneously but out of phase prior to stimulating the rest of analysis bands using the standard in phase current steering technique.</p