A Prospective Comparative Observational Study of Clinical Efficacy of Isobaric Ropivacaine 0.75% with of Isobaric Bupivacaine 0.5% Intrathecally in Elective Inguinal Hernia Repair Surgeries.

AIMS: To evaluate the efficacy of intrathecal isobaric Ropivacaine and its comparison with intrathecal isobaric Bupivacaine in elective inguinal hernia repair surgeries. SETTINGS AND DESIGN: A prospective, randomized study was conducted in a tertiary care hospital with 80 patients of ASA grade I-III undergoing elective inguinal hernia repair surgery under spinal anaesthesia. Ethical committee clearance and written consent taken. The patients were randomly divided into two equal groups to the Ropivicaine group (Group R) and to theBupivicaine group (Group B). Parameters observed were onset and duration of sensory and motor block, maximum sensory level achieved degree of motor blockade, two segment regression, and haemodynamic changes. RESULTS: The development of sensory block was faster with Isobaric Ropivicaine (12.1 ± 4.9 minutes) as than isobaric Bupivicaine (13.94 ± 4.52 minutes) but the difference was not statistically significant. Onset of Grade III Motor block was longer with Isobaric Ropivicaine (8.51 ± 3.39 minutes) as compared to isobaric Bupivicaine (8.51 ± 3.39 minutes), but the difference was not statistically significant. Time of Complete Sensory Regression was significantly shorter with Isobaric Ropivicaine (212.69 ± 27.31 minutes) with statistical significance. Time to complete motor recovery was significantly shorter in Ropivacaine group (253.38 ± 27.13 minutes)as compared to Bupivacaine group (258.55 ± 35.81min), with statistical significance. Time to achieve discharge criteria was relatively shorter with Isobaric Ropivicaine. Haemodynamic Parameters did not differ significantly in both the groups during the entire study period. CONCLUSION: Intrathecal administration of isobaric Ropivacaine (0.75%) 15 mg provides similar quality of spinal anaesthesia but of significantly shorter duration, maintaining similar hemodynamic stability and discharge criteria without significant adverse effects when compared to isobaric Bupivicaine (0.5%) 10 mg.

Preparation, in vitro characterization, and in vivo pharmacokinetic evaluation of respirable porous microparticles containing rifampicin.

This study aimed to prepare and evaluate rifampicin microparticles for the lung delivery of rifampicin as respirable powder. The microparticles were prepared using chitosan by the spray-drying method and evaluated for aerodynamic properties and pulmonary drug absorption. To control the drug release, tripoly-phosphate in different concentrations 0.6, 0.9, 1.2, and 1.5 was employed to get a sustained drug release profile. The microparticles were evaluated for drug loading, % entrapment efficiency, tapped density, morphological characteristics, and in vitro drug release studies. Aerosol properties were determined using the Andersen cascade impactor. Porous microparticles with particle sizes (d0.5) less than 10 µm were obtained. The entrapment of rifampicin in microparticles was up to 72%. In vitro drug release suggested that the crosslinked microparticles showed sustained release for more than 12 hrs. The drug release rate was found to be decreased as the TPP concentration was increased. The microparticles showed a fine particle fraction in the range of 55-63% with mass median aerodynamic diameter (MMAD) values below 3 µm. The in vivo pulmonary absorption of the chitosan microparticles suggested a sustained drug release profile up to 72 hrs with an elimination rate of 0.010 per hr. The studies revealed that the spray-dried porous microparticles have suitable properties to be used as respirable powder in rifampicin delivery to the lungs.

Comparative pharmacokinetic studies of fast dissolving film and oral solution of ondansetron in rats.

Ondansetron, selective serotonin (5-HT3) receptor blocker, is used in treating chemotherapy induced nausea and vomiting in cancer patients. Mouth dissolving films containing ondansetron were developed to have better onset and patient compliances. The drug content of prepared films was within 85%-115%. The films were found to be stable for 4 months when stored at 40 %°C and 75% RH. In-vitro dissolution studies suggested a rapid disintegration, in which most of ondansetron was released (91.5±3.4%) within 90 sec. Subsequently, Sprague-Dawley rats were used to compare pharmacokinetic parameters of the formulated films with oral administration of pure drug solution. Pharmacokinetic parameters were similar between the two groups in which AUC0-t (ng h/ml), AUC0-∞ (ng h/ml), Cmax (ng/ml), Tmax (min), Kel (h(-1)) and t1/2 (h) of reference was 109.091±15.73, 130.32±18.56, 28.5±4.053, 60, 0.1860±0.0226, and 3.771±0.498 respectively; and for formulated film 113.663±16.64, 151.79±16.54, 30±3.51, 60, 0.1521±0.0310 and 4.755±0.653 respectively. These results suggest that the fast dissolving film containing ondansetron is likely to become one of the choices to treat chemotherapy induced nausea and vomiting.

Formulation development and evaluation of mouth dissolving film of domperidone.

The present investigation was undertaken with the objective of formulating mouth dissolving film(s) of the antiemetic drug Domperidone to enhance the convenience and compliance by the elderly and pediatric patients. Domperidone is a drug of choice in case of nausea and vomiting produced by chemotherapy, migraine headaches, food poisoning and viral infections. It causes dopamine (D2 and D3) receptor blockage both at the chemoreceptor trigger zone and at the gastric level. It shows high first pass metabolism which results in poor bioavailability (10-15%). In view of high first pass metabolism and short plasma half-life it is an ideal candidate for rapid release drug delivery system. The solid dispersions of Domperidone were prepared with the use ß-cyclodextrin in various ratios (1:1, 1:2, 1:3) and solubility study was performed to determine the ratio in which solubility of Domperidone was highest (1:3). The selected solid dispersions were then utilized for the preparation of film by solvent casting method utilizing HPMC E15 as a film forming agent and PEG-400 as plasticizer. Five formulae were prepared and were evaluated for their in vitro dissolution characteristics, in vitro disintegration time, and their physico-mechanical properties. The promising film (F1) showed the greatest drug dissolution (more than 75% within 15 min), satisfactory in vitro disintegration time (45 sec) and physico-mechanical properties that are suitable for mouth dissolving films.

Formulation and evalution of montelukast sodium - chitosan based spray dried microspheres for pulmonary drug delivery.

The objective of present work was to prepare microspheres of montelukast sodium using a natural polymer- chitosan by spray drying method by using glutaraldehyde as a cross linking agent. The microspheres were characterized for size, shape, dissolution, swelling and mucoadhesion. It was observed that, all microspheres were spherical in shape with narrow size distribution. Microspheres had mean particle size of 7-12 µm, with % encapsulation efficiency of 78-86%. The % yield was 32-49% and drug load was 48-53%. With the increase in proportion of chitosan in formulation mucoadhesive strength was increase and also increased in particle size of microspheres. As the drug:polymer ratio increase drug loading was increase and % encapsulation efficiency was also increase.

Development and characterization of pharmacokinetic parameters of fast-dissolving films containing levocetirizine.

A fast-dissolving film containing levocetirizine, a non-sedative antihistamine drug, was developed using pullulan, xanthan gum, propylene glycol, and tween 80 as the base materials. The drug content of the prepared films was within an acceptable limit as prescribed by the USP. The film exhibited excellent stability for four months when stored at 40 °C and 75% humidity. In vitro dissolution studies suggested a rapid disintegration, in which most of levocetirizine (93.54 ± 3.9%) dissolved within 90 seconds after insertion into the medium. Subsequently, Sprague-Dawley rats were used to compare the pharmacokinetic properties of the film preparation administered to the oral cavity, to those with oral administration of the pure drug solution. The pharmacokinetic parameters were similar between the two groups in which AUC(0-t) (ng h/ml), AUC(0-∞) (ng h/ml) C(max) (ng/ml), T(max) (min), K(el) (h(-1)), and t(1/2) (h) of the reference were 452.033 ± 43.68, 465.78 ± 48.16, 237.16 ± 19.87, 30, 0.453 ± 0.051, and 1.536 ± 0.118, respectively, for the film formulation 447.233 ± 46.24, 458.22 ± 46.74, 233.32 ± 17.19, 30, 0.464 ± 0.060, and 1.496 ± 0.293, respectively. These results suggest that the present levocetirizine containing fast-dissolving film is likely to become one of the choices to treat different allergic conditions.

Morphologies near cloud point in aqueous ionic surfactant: scattering and NMR studies.

Clouding phenomenon in ionic surfactant solution is fairly a new addition to the conventional phenomenon observed with nonionic counterpart. Various scattering and spectroscopic techniques, dynamic light scattering (DLS), small angle neutron scattering (SANS), and nuclear magnetic resonance (NMR), have been used to draw information regarding the aggregate morphologies (formed by an ionic surfactant, tetra-n-butylammonium dodecylsulphate, TBADS) when the surfactant solution passes through the cloud point (CP). DLS measurements have shown that two morphologies are present when the system approaches the CP. The data revealed that individual micelles (~5 nm) convert to giant aggregates (~500 nm) over the range of temperature including the CP. SANS experiments have been performed to draw the information regarding individual micellar fraction below and above the CP. NMR spectra at different temperatures have been collected for TBADS solution. The broadening and the downfield shift of -N-CH(2) and -O-CH(2) proton peaks support the micellar growth as the sample was heated. The above peaks show splitting (into two each) confirming the presence of two morphologies around the CP. It is noted that conversion of only a small fraction of individual micelles is responsible for the clouding.

Simultaneous analysis of eprosartan and hydrochlorothiazide in tablets by high-performance liquid chromatography.

OBJECTIVE: A simple, precise and accurate isocratic reversed phase (RP) column high-performance liquid chromatographic (HPLC) method has been developed for simultaneous analysis of eprosartan (EPR) and hydrochlorothiazide (HCT) in tablet formulations. MATERIALS AND METHODS: Isocratic RP-HPLC separation was achieved on phenomenex C18 column (250 × 4.6 mm i.d., 5 µm particle size) using mobile phase composed of 0.5% formic acid-methanol-acetonitrile [(80 : 25 : 20 v/v/v) pH, 2.80 ± 0.04] at a flow rate of 1.0 ml/min. The retention time for EPR and HCT was 7.69 ± 0.10 and 4.24 ± 0.09 minutes, respectively. The detection was performed at 272 nm. RESULTS: The method was linear in the concentration range of 60-600 µg/ml for EPR and 2.5-25 µg/ml for HCT with a correlation coefficient of 0.9992 and 0.9997, respectively. The repeatability for six samples was 0.53 and 0.61 % RSD for EPR and HCT, respectively. The accuracy (recovery) was found to be in the range of 99.46 to 100.61% for EPR and 99.06 to 100.93% for HCT, respectively. CONCLUSIONS: The method was validated and successfully used for determination of the drugs in tablets.

Development and validation of a high-performance liquid chromatographic method for determination of eprosartan in bulk drug and tablets.

A simple, precise, and accurate isocratic RP-HPLC method was developed and validated for determination of eprosartan in bulk drug and tablets. Isocratic RP-HPLC separation was achieved on a Phenomenex C18 column (250 x 4.6 mm id, 5 microm particle size) using the mobile phase 0.5% formic acid-methanol-acetonitrile (80 + 25 + 20, v/v/v, pH 2.80) at a flow rate of 1.0 mL/min. The retention time of eprosartan was 7.64 +/- 0.05 min. The detection was performed at 232 nm. The method was validated for linearity, precision, accuracy, robustness, solution stability, and specificity. The method was linear in the concentration range of 10-400 microg/mL with a correlation coefficient of 0.9999. The repeatability for six samples was 0.253% RSD; the intraday and interday precision were 0.21-0.57 and 0.33-0.71% RSD, respectively. The accuracy (recovery) was found to be in the range of 99.86-100.92%. The drug was subjected to the stress conditions hydrolysis, oxidation, photolysis, and heat. Degradation products produced as a result of the stress conditions did not interfere with detection of eprosartan; therefore, the proposed method can be considered stability-indicating.

Mucoadhesive bilayer tablets of propranolol hydrochloride.

The purpose of this research was to study mucoadhesive bilayer buccal tablets of propranolol hydrochloride using the bioadhesive polymers sodium alginate (Na-alginate) and Carbopol 934P (CP) along with ethyl cellulose as an impermeable backing layer. The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, mucoadhesive strength, swelling index, in vitro drug release, ex vivo drug permeation, ex vivo mucoadhesion, and in vivo pharmacodynamics in rabbits. Tablets containing Na-alginate and CP in the ratio of 5:1 (F2) had the maximum percentage of in vitro drug release without disintegration in 12 hours. The swelling index was proportional to Na-alginate content and inversely proportional to CP content. The surface pH of all tablets was found to be satisfactory (7.0 +/- 1.5), close to neutral pH; hence, buccal cavity irritation should not occur with these tablets. The mechanism of drug release was found to be non-Fickian diffusion and followed zero-order kinetics. The formulation F4 was optimized based on good bioadhesive strength (28.9 +/- 0.99 g) and sustained in vitro drug permeation (68.65% +/- 3.69% for 12 hours). The behavior of formulation F4 was examined in human saliva, and both the drug and the buccal tablet were found to be stable. The formulation F4 was applied to rabbit oral mucosa for in vivo studies. The formulation inhibited isoprenaline-induced tachycardia. The studies conducted in rabbits confirmed the sustained release as compared with intravenous administration.