Background:This study was undertaken to evaluate the analgesic effect of the combination of epidural Clonidine with Bupivacaine versus epidural Bupivacaine alone in patients undergone knee replacement surgery.Materials and Methods:A randomized double-blind design was used, and 60 adult patients (40-60 years) of ASA grade I and II scheduled for post-operative pain relief in total knee replacement surgeries by epidural Clonidine were studied. Patients received either an epidural Clonidine (1μg/kg) with Bupivacaine (1.5mg/kg) group CL (n=30) or Bupivacaine alone group CT (n=30) for Knee replacement surgeries. The pain score, blood pressure, heart rate, respiratory rate were measured at fixed times during the first 24 h after operation. Onset and duration of sensory and motor blockade, duration of analgesia, and analgesic requirement were compared.Results:The onset of sensory anesthesia was faster (493.8±31.66 in sec.) and the duration was significantly longer in Clonidine group (334.2 min). Requirement of supplementary analgesia (Inj. diclofenac) was markedly decreased in Clonidine group as evident from the findings that in control group 18 patients required 3 supplemental analgesic doses in first 24 hours as compared to only 3 patients in Clonidine group. Epidural Clonidine produced a significant decrease (P less than 0.05) in heart rate and blood pressure, whereas the respiratory rate was not affected. We also observed for side effects in both the groups. Incidence of significant hypotension was higher, 8 patients (26%) in Clonidine group compared to 2 patient (6%) in control group. Incidence of dryness of mouth was higher, 12 patients (48%) in Clonidine group compared to 5 (18%) in control group.Conclusion:The addition of Clonidine to Bupivacaine epiduraly prolongs motor and sensory block and analgesia, without an increased incidence of side effects.

A rapid, selective and stability-indicating high performance thin layer chromatographic method was developed and validated for the simultaneous estimation of olanzapine and fluoxetine in combined tablet dosage form. Olanzapine and fluoxetine were chromatographed on silica gel 60 F254 TLC plate using methanol:toluene (4:2 v/v) as the mobile phase and spectrodensitometric scanning-integration was performed at a wavelength of 233 nm using a Camag TLC Scanner III. This system was found to give compact spots for both olanzapine (Rf value of 0.63±0.01) and fluoxetine (Rf value of 0.31±0.01). The polynomial regression data for the calibration plots showed good linear relationship with r2=0.9995 in the concentration range of 100-800 ng/spot for olanzapine and 1000-8000 ng/spot for fluoxetine with r2=0.9991. The method was validated in terms of linearity, accuracy, precision, recovery and specificity. The limit of detection and the limit of quantification for the olanzapine were found to be 30 and 100 ng/spot, respectively and for fluoxetine 300 and 1000 ng/spot, respectively. Olanzapine and fluoxetine were degraded under acidic, basic and oxidation degradation conditions which showed all the peaks of degraded product were well resolved from the active pharmaceutical ingredient. Both drugs were not further degraded after thermal and photochemical degradation. The method was found to be reproducible and selective for the simultaneous estimation of olanzapine and fluoxetine. As the method could effectively separate the drugs from their degradation products, it can be employed as a stability-indicating method.

This paper describes validated high-performance liquid chromatographic (LC) and high-performance thin-layer chromatographic (TLC) methods for the simultaneous estimation of olanzapine and fluoxetine in pure powder and tablet formulations. The LC separation was achieved on a Lichrospher 100 RP-180, C18 column (250 mm, 4.0 mm id, 5 m) using 0.05 M potassium dihydrogen phosphate buffer (pH 5.6 adjusted with o-phosphoric acid) acetonitrile (50 + 50, v/v) as the mobile phase at a flow rate of 1 mL/min and ambient temperature. The TLC separation was achieved on aluminum sheets coated with silica gel 60F254 using methanoltoluene (40 + 20, v/v) as the mobile phase. Quantitation was achieved by measuring ultraviolet absorption at 233 nm over the concentration range of 1070 and 40280 g/mL with mean recovery of 99.54 0.89 and 99.73 0.58% for olanzapine and fluoxetine, respectively, by the LC method. Quantitation was achieved by measuring ultraviolet absorption at 233 nm over the concentration range of 100800 and 4003200 ng/spot with mean recovery of 101.53 0.06 and 101.45 0.35% for olanzapine and fluoxetine, respectively, by the TLC method with densitometry. These methods are simple, precise, and sensitive, and they are applicable for simultaneous determination of olanzapine and fluoxetine in tablet formulations.

Scheme illustrating the sustainable preparation of deep eutectic solvent derivatives (DESDs), their biological response and water-insoluble hydrophobic drug dissolution trend.