Liposomes as potential carriers for ketorolac ophthalmic delivery: formulation and stability issues

ABSTRACT Drug delivery to treat ocular disorders locally is a challenging endeavor. Traditional ocular dosage form - eye drops - exhibits poor availability, consequently inefficient therapeutic response. The objective of the study was to formulate and characterize a ketorolac tromethamine ocular system with a prolonged release pattern based on liposomes as a vesicular carrier and to design once daily liquid preparation realizing the thermal in situ gelation principle. Liposomes were prepared by film hydration method. The influence of cholesterol concentration, pH and volume of hydration medium, and type and concentration of charging imparting agents were studied. Liposomes were characterized via, morphological examination, vesicular size, and encapsulation efficiency, and in vitro release performance, moreover its stability was assessed. The results obtained highlighted that liposomes showed a closed vesicular multi-lamellar structure. Ketorolac was successfully encapsulated within the liposomal structure in a cholesterol and charge inducing agent concentration-dependent behaviour. The dispersion of liposomes within thermosensitive Poloxamer in situ gel was able to retard the release of the drug by diffusion providing a controlled prolonged delivery. The liposomal formulations were physically stable for six months. Ketorolac tromethamine in situ liposomal gel representing an efficient alternative in terms of ocular retention and patient compliance when compared with conventional eye drops

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien–Dindo Grades III–V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49–2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46–0.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease