In the present work, the antiglaucoma drug, acetazolamide, was formulated as microsponges in situ gel for ocular drug delivery aiming an improved therapeutic efficacy and reduction in the systemic side effects of oral acetazolamide. The microsponges were prepared by the quasi emulsion solvent diffusion method and were incorporated into 25% pluronic F-127 in situ gel. Ethyl cellulose polymer in different proportions with drug was used to prepare the microsponges. Different parameters were evaluated to select the best formulation. The formula S2 with drug to polymer ratio (2:1) showed high entrapment efficiency of about 82% and mean particle size of about 10 µm with polydispersity index (PDI) of 0.22, which are suitable characters for ocular delivery. The in situ gels were evaluated for physicochemical properties (pH, gelling capacity, gelation time and rheological properties) and in vivo studies. S2 formulation showed higher therapeutic efficacy compared to free drug in gel. It was non irritant to the rabbit's eye. These results indicated that acetazolamide microsponges in situ gel have potential ability for ophthalmic delivery.

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The objective of this study was to investigate the influence of simultaneous factors that potentially keep patients far from achieving target INR range at discharge in hospitalized patients. Prospective cross-sectional observational study conducted at the Cardiology Department and Intensive Care Unit (ICU) of the Assiut University Hospitals. One-hundred and twenty patients were enrolled in the study from July 2013 to January 2014. Outcome measures were discharge INRs, bleeding and thromboembolic episodes. Bivariate analysis and multinomial logistic regression were conducted to determine independent risk factors that can keep patients outside target INR range. Patients who were newly initiated warfarin on hospital admission were given low initiation dose (2.8 mg ± 0.9). They were more likely to have INR values below 1.5 during hospital stay, 13 (27.7%) patients compared with 9 (12.3%) previously treated patients, respectively (p = .034). We found that the best predictors of achieving below target INR range relative to within target INR range were; shorter hospital stay periods (OR, 0.82 for every day increase [95% CI, 0.72-0.94]), being a male patient (OR, 2.86 [95% CI, 1.05-7.69]), concurrent infection (OR, 0.21 [95% CI, 0.07-0.59]) and new initiation of warfarin therapy on hospital admission (OR, 3.73 [95% CI, 1.28-10.9]). Gender, new initiation of warfarin therapy on hospital admission, shorter hospital stay periods and concurrent infection can have a significant effect on discharge INRs. Initiation of warfarin without giving loading doses increases the risk of having INRs below 1.5 during hospital stay and increases the likelihood of a patient to be discharged with INR below target range. Following warfarin dosing nomograms and careful monitoring of the effect of various factors on warfarin response should be greatly considered.

The objective of this study was to investigate the effect of polypharmacy and high doses of amoxicillin/clavulanate on warfarin response in hospitalized patients. This was a prospective cross-sectional observational study on 120 patients from July 2013 to January 2014. Potentially interacting drugs were classified according to their tendency of increasing international normalized ratio (INR) or bleeding risk. The 87.5% of patients prescribed high-dose amoxicillin/clavulanate (10-12 g daily) compared with 28.9% of patients prescribed a normal dose (up to 3.6 g daily) had INR values ≥ 4 during the hospital stay (P ≤ .001). Increased number of potentially interacting drugs that are known to increase INR was a significant predictor of having INR values ≥ 4 (OR, 2.5; 95%CI, 1.3-4.7), and increased number of potentially interacting drugs that are known to increase bleeding risk was a significant predictor of experiencing bleeding episodes (OR, 3.1; 95%CI, 1.3-7.3). High doses of amoxicillin/clavulanate were associated with a higher risk of over-anticoagulation when combined with warfarin than were normal doses. Increased risk of having INR ≥ 4 and bleeding events was associated with increased numbers of potentially interacting drugs prescribed, indicating that polypharmacy is a problem of concern. Frequent monitoring of warfarin therapy along with patients' medications is necessary to avoid complications.

Journal of Liquid ChromatographyPublication details, including instructions for authors and subscription information: ABSTRACT A rapid, simple and sensitive high performance liquid chromatographic (HPLC) assay for the quantitation of diclofenac (DF) in dog plasma has been developed. Mefenamic acid (MA) was used as the internal standard. After acidification, DF and MA were extracted from plasma into chloroform.Separation was achieved using a C18 reversed phase column. The retention times of DF and MA were 3.8 and 6.3 min., respectively at the flow rate of 1.5 ml/min. The DF interday standard plots (n=4) were highly linear (n0.99) over the concentration range of 0.01 to 10 pg/ml. DF mean recovery was 98% 2 5.5, and the % CV of intra-and inter-day sample analyses ranged from 2.6 to 10.8% for the entire calibration range. The limit of quantification of DF in plasma was 0.01 pg/rnl with the CV of 9.4%.The method was applied f o r the determination of the pharmacokinetic parameters of DF given by oral and iv bolus administration to dogs.

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5-Fluorouracil is widely used for treatment of colorectal cancer and is provided as intravenous bolus or infusion because it has erratic oral bioavailability. Diarrhea and myelosuppression are potential and the major side effects of the intravenous administration route. This work was aimed to develop colon-targeted delivery of 5-Fluorouracil microsponges so that, the oral bioavailability enhanced and the side effects could be potentially reduced. Quassi-emulsion solvent diffusion method was used to prepare 5-Fluorouracil microsponges using polyethylene glycol as an emulsifier. Different formulae were prepared with different composition and processing factors. The entrapment efficiency 5-Fluorouracil in these formulae ranged from 17.81 to 78.61%, the particle size of the prepared microsponges ranged from 87 to 229 µm and the % cumulative drug released after 24 hours ranged from 47.7 to 98.58%. The prepared microsponges were subjected to compatibility studies as Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Thus 5-fluorouracil microsponges considered as a promising system for the colon-specific delivery that has potential for future use as an anticancer therapy for colorectal cancer.