Impact of including regional anaesthesia in enhanced recovery protocols: a scoping review.

Regional anaesthesia (RA) is often included in enhanced recovery protocols (ERPs) as an important component of a bundle of interventions to improve outcomes after surgery. We sought to delineate whether the literature supports the use of RA in this setting with regard to commonly measured outcomes. We further sought to assess whether such improvements would translate into positive impacts on healthcare value as defined by the Institute for Healthcare Improvement Triple Aim. We conducted a scoping review to address our objectives. Studies of ERPs that included RA and reported at least one outcome of interest in comparison to a control group were included. MEDLINE, EMBASE, CENTRAL, CDSR, PROSPERO, and the NHS Economic Evaluation Database were searched up to May 2015. Two reviewers assessed studies and extracted data. Of 695 identified citations, 58 studies were included for analysis. The majority (53%) were in colorectal surgery. Positive impacts of RA on all outcomes were identified; however, value-based outcomes were rarely reported. Where value-based outcomes were reported, RA appears to have a positive impact on global measures of health and function and on economic outcomes. Existing literature supports a positive impact of RA on ERP outcomes, which may be reflected in improved healthcare value. In order to justify the value of RA in ERPs, a future focus on appropriate measures is needed to align research with widely accepted frameworks, such as the Triple Aim.

The effect of gelatin cross-linking on the bioequivalence of hard and soft gelatin acetaminophen capsules.

PURPOSE: To determine if changes in the in vitro dissolution of hard and soft gelatin acetaminophen capsules, which result from gelatin crosslinking, are predictive of changes in the bioavailability of the capsules in humans. METHODS: Both hard and soft gelatin capsules were "stressed" by a controlled exposure to formaldehyde, resulting in unstressed, moderately stressed and highly stressed capsules. In vitro dissolution studies were conducted using water or SGF with and without pepsin as the media. Separate 24-subject, 3-way crossover human bioequivalence studies were performed on the unstressed and stressed acetaminophen capsules. Plasma acetaminophen was determined by high performance liquid chromatography (HPLC) for 12 hr after each dose. RESULTS: The in vitro rate of dissolution of hard and soft gelatin capsules was decreased by crosslinking. The bioequivalence studies showed that both hard and soft gelatin capsules, which failed to meet the USP dissolution specification in water, but complied when tested in SGF containing pepsin, were bioequivalent to the unstressed control capsules. The capsules that were cross-linked to the greatest extent were not bioequivalent to the unstressed control capsules, based on Cmax. A trend toward an increase in Cmax with increased level of cross-linking was observed, but this was only significant for the severely stressed capsules. CONCLUSIONS: On the basis of this study a two-tier in vitro dissolution test was developed using enzymes to distinguish between bioequivalent and bioinequivalent gelatin capsules.

Comparative pharmacokinetic study of a floating multiple-unit capsule, a high-density multiple-unit capsule and an immediate-release tablet containing 25 mg atenolol.

The purpose of this study was to evaluate the possible advantages of floating and high-density dosage forms and their influence on pharmacokinetic parameters. Atenolol was chosen as a model drug because of its poor absorption in the lower gastrointestinal tract. Three formulations containing 25 mg atenolol, a floating multiple-unit capsule, a high-density multiple-unit capsule, and an immediate-release tablet were compared with respect to estimated pharmacokinetic parameters. The two multiple-unit dosage forms were composed of compressed minitablets and had sustained release properties. The bioavailability of the two gastroretentive preparations with sustained release characteristics was significantly decreased when compared to the immediate-release tablet. The floating minitablets seemed to be retained longer in the stomach than the high-density dosage form. The first atenolol concentration detectable in the plasma and the time to peak Tmax were delayed for the floating dosage form. For the parameters Cmax and AUC 0-infinity, the lower limit of the 90% confidence interval was outside the bioequivalence range (0.80-1.25). This study showed that it was not possible to increase the bioavailability of a poorly absorbed drug such as atenolol using gastroretentive formulations. Atenolol absorption was delayed and the maximum plasma concentration was diminished.

The effect of cross-linking on the in vivo disintegration of hard gelatin capsules.

PURPOSE: To evaluate if the cross-linking of gelatin affects in vivo capsule disintegration. METHODS: Scintigraphic investigation in nine healthy volunteers to provide for a real time visualisation of capsule disintegration. RESULTS: The moderately stressed capsules failed the USP dissolution specification for acetaminophen capsule when tested in water and conventional SGF but passed with the addition of pepsin. Moderately stressed capsules started to disintegrate at 10 +/- 6 minutes (range 6 to 24 minutes) compared to 8 +/- 2 minutes (range 5 to 11 minutes) for the unstressed capsule. CONCLUSIONS: The results of the study clearly demonstrate that with the incisive technique of gamma scintigraphy there are no differences in the in vivo disintegration properties of moderately stressed and unstressed capsules.

Buoyancy and drug release patterns of floating minitablets containing piretanide and atenolol as model drugs.

The purpose of this study was to evaluate factors for improving the in vitro buoyancy and the drug release characteristics of floating minitablets containing either piretanide or atenolol as model drugs. The buoyancy of the minitablets was achieved either by the swelling of the excipient or by incorporation of the gas-generating agent sodium bicarbonate. Resultant-weight kinetics were performed in order to evaluate the buoyancy. The release rate of the poorly soluble drug piretanide was enhanced by increasing its solubility or by promoting the erosion of the minitablets. For the sparingly soluble drug atenolol, the minitablets were coated with different ratio of insoluble polymer in order to diminish the release rate of this drug. The swelling of a hydrophilic excipient was not sufficient to obtain floating minitablets. The buoyancy of the minitablets containing either piretanide or atenolol was greatly improved by adding sodium bicarbonate as well as by a wet granulation. The most satisfactory improvement in the release rate of piretanide was achieved using a solid dispersion with povidone, thus increasing the drug solubility concomitantly with the increase of the minitablets' erosion. Regarding atenolol, minitablets containing 7% sodium bicarbonate and coated with Eudragit NE30D:RS 70:30 gave satisfactory results concerning buoyancy and drug release rate. This study showed that it was possible to produce minitablets containing either piretanide or atenolol, which have a positive resultant-weight during more than 6 hr and satisfactory release profiles.