Gastric electric stimulator versus gastrectomy for the treatment of medically refractory gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) and laparoscopic gastrectomy (LG) are known therapeutic options for medically refractory gastroparesis (MRG) although there are limited data comparing their outcomes. We aim to compare clinical outcomes between patients undergoing GES vs upfront LG for the treatment of MRG while examining factors associated with GES failure and conversion to LG. METHODS: We retrospectively analyzed 181 consecutive patients who underwent GES or LG for MRG at our institution from January 2003 to December 2017. Data collection consisted of chart review and follow-up telephone survey. Statistical analysis utilized Chi-squared, ANOVA, and multivariable logistic regression. RESULTS: Overall, 130 (72%) patients underwent GES and 51 (28%) LG as primary intervention. GES patients were more likely to have diabetic gastroparesis (GES 67% vs LG 39%, p < 0.001), while primary LG patients were more likely to have post-surgical gastroparesis (GES 5% vs LG 43%, p < 0.001). Postoperatively, primary LG patients had higher rates of major in-hospital morbidity events (GES 5% vs LG 18%, p = 0.017) and longer hospital stays (GES 3 vs LG 9 days, p < 0.001). However, over a mean 35-month follow-up period, there were no differences in the rates of major morbidity, readmissions, or mortality. Multivariable regression analysis revealed patients undergoing GES as a primary intervention were less likely to report improvement in symptoms on follow-up compared to primary LG patients OR 0.160 (95% CI 0.048-0.532). Additionally, patients who converted to LG from GES were more likely to have post-surgical gastroparesis as the primary etiology. CONCLUSION: GES as a first-line surgical treatment of MRG was associated with worse outcomes compared to LG. Post-surgical etiology was associated with an increased likelihood of GES failure, and in such patients, upfront gastrectomy may be a superior alternative to GES. Further studies are needed to determine patient selection for operative treatment of MRG.

Electrostatic Precipitation of Submicron Particles in a Molten Carrier.

Recently, submicron particles have been discussed as a means to increase the bioavailability of poorly water-soluble drugs. Separation of these small particles is done with both fibre and membrane filters, as well as electrostatic precipitators. A major disadvantage of an electrostatic precipitator (ESP) is the agglomerate formation on the precipitation electrode. These agglomerates frequently show low bioavailability, due to the decreased specific surface area and poor wettability. In this work, a new melt electrostatic precipitator was developed and tested to convert submicron particles into a solid dispersion in order to increase the bioavailability of active pharmaceutical ingredients. The submicron particles were generated by spray drying and transferred to the ESP, where the collection electrode is covered with a melt, which served as matrix after solidification. The newly developed melt electrostatic precipitator was able to collect isolated naproxen particles in a molten carrier. A solid naproxen xylitol dispersion was prepared, which showed a reduction of the dissolution time by 82%, and a release of 80% of the total drug, compared to the physical mixture.

Preparation of submicron drug particles via spray drying from organic solvents.

Manufacturing poorly water-soluble active pharmaceutical ingredients (API) with sufficient bioavailability is a significant challenge in pharmaceutical research. A higher bioavailability can reduce both the applied dosage and the side effects for the patient. One method of increasing the bioavailability is to reduce the particle size of the drug down to the nanoscale. An innovative procedure for the preparation of particles in the submicron size range is spray drying with aerosol conditioning, followed by subsequent separation of the particles in an electrostatic precipitator (ESP). This process has been tested before in an earlier work with aqueous model substances at high production rates (1 g/h) and narrow particle-size distributions (mannitol: d50,0 = 455 nm, span = 0,8) in the submicron range. Spray drying from an aqueous solution with low drug concentrations (<1 wt-%) leads to particles in the lower nanosize range, but the low concentrations make this process inefficient. A custom-made plant was modified in order to handle the organic spray-drying process. In addition, explosion protection had to be considered. This work focuses on the spray drying of submicron particles from organic solvents for the purpose of increasing the dissolution rate of the API griseofulvin. API particles were successfully produced in the submicron size-range, characterized and the dissolution behavior was investigated. The dissolution time to dissolve 80% of the drug, t80, was reduced from 21.5 min for the micronized grade API to 8.5 min for the submicron product.

Preparation of spray dried submicron particles: Part A - Particle generation by aerosol conditioning.

The preparation of submicron-sized particles is relevant in chemical, food and pharmaceutical applications. In pharmaceutics, spray dried submicron-sized particles (0.1-1 µm) can increase the dissolution rate as well as the solubility of poorly water-soluble drugs. Since the particle size during spray drying is mainly influenced by the droplet size, the preparation of uniform droplets smaller than 3 µm is of particular interest. In this work, a two-fluid nozzle was combined with a cyclone droplet separator. Droplets larger than the cut-off size were separated with a cyclone droplet separator and returned to the liquid feed. The aerosol at the outlet of the droplet separator was subsequently dried. The drop size of the conditioned aerosol was small, d50,3=2 µm, and independent of the liquid-to-gas mass flow ratio and the viscosity of the liquid feed. Thus it only depended on the characteristics of the separator. Finally, the dried particles were spherical in shape and in the submicron-sized range.

Preparation of spray dried submicron particles: Part B - Particle recovery by electrostatic precipitation.

The low bioavailability of poorly water-soluble drugs is currently one of the major focuses of pharmaceutical research. One strategy currently being investigated to overcome this limitation is to decrease the particle size of the active pharmaceutical ingredients (API). An innovative process for this is spray drying with spray conditioning, which can produce submicron particles. One challenge resulting from this process is the recovery of these dispersed particles from a gas flow. Electrostatic precipitation is a common technique for air purification purposes, but an adapted electrostatic precipitator (ESP) design is necessary to achieve high collection efficiencies. The ESP design in this work uses the precipitation method of Penney filters which separates charging and collection into two stages. The ESP dimensions depend on various assumptions and simplifications. Several experiments were conducted to assess the performance of the ESP and characterize its behaviour in long-term tests. The crucial parameters in the charging process are the residence time as well as the operating voltage. These constraints were examined to enhance the collection efficiency. Based on these tests it was possible to determine a suitable charging length as well as the dimensions of the collection stage. In conclusion, an ESP customized for collecting particles in the range of 0.1-1 µm was designed, built and tested, and collection efficiencies higher than 99% were achieved for submicron particle size distributions. For a robust process continuous cleaning of the charging stage is necessary.