Raju Jukanti

Enhanced bioavailability of exemestane via proliposomes based transdermal delivery.

Exemestane, a novel steroidal aromatase inactivator used in the treatment of advanced breast cancer has limited bioavailability (42%) due to poor solubility, extensive first-pass metabolism, and also the absorption is dependent on formulation type and food. The present study is aimed to evaluate the feasibility of proliposomes for transdermal delivery of exemestane. The prepared proliposomes were characterized for size, zeta potential, and entrapment efficiency. The size of the vesicles was found to be between 440 and 700 nm with high entrapment efficiency for the formulation containing greater amounts of phosphatidylcholine. Differential scanning calorimetry and Fourier transform infrared studies were performed to understand the phase transition behavior and mechanism for skin permeation, respectively. The drug release across cellophane membrane follows zero-order kinetics by diffusion. Ex vivo permeation enhancement assessed from flux, permeability coefficient, and enhancement ratio were significantly higher for proliposome gels compared with control. A significant improvement in the bioavailability (2.4-fold) was observed from optimized proliposome gel compared with control (oral suspension). The stability data reveal that the formulations are more stable when stored at 4°C. In conclusion, proliposomal gels offer potential and prove to be efficient carriers for improved and sustained transdermal delivery of exemestane.

Solubility enhancement and physicochemical characterization of carvedilol solid dispersion with Gelucire 50/13

The objective of the study was enhancement of dissolution of poorly soluble carvedilol by solid dispersions (SDs) with Gelucire 50/13 using solvent evaporation method. The solubility of carvedilol showed linear increase with increasing concentrations of Gelucire indicating AL type solubility diagrams. SDs characterized for physicochemical characteristics using differential scanning calorimetry and X-ray diffractometry revealed transformation of crystalline form of drug to amorphous form which was confirmed by scanning electron micrographs. Further fourier transform infrared spectroscopy results suggested there is no drug carrier interaction. From the dissolution parameters such as mean dissolution time, dissolution efficiency and drug release rate, improved dissolution characteristics for SDs were observed compared with physical mixture and pure drug. Thus SDs of carvedilol in Gelucire 50/13 showed enhanced solubility and dissolution rate compared to pure drug.

Design and evaluation of taste masked dextromethorphan hydrobromide oral disintegrating tablets

Design and evaluation of taste masked dextromethorphan hydrobromide oral disintegrating tablets The present study is aimed to develop dextromethorphan hydrobromide (DXM) oral disintegrating tablets (ODT) with acceptable palatability to help patients of all age groups. The bitter taste of the drug was masked by binding the drug to ion exchange resin. The effect of the particle size of resin on drug loading was studied. In vitro and in vivo disintegration time and in vitro drug release studies were performed. Drug loading increased significantly with a decrease in the particle size of the resin. DSC and XRPD studies reveal that the molecular state of the drug changed from crystalline to amorphous form. The dissolution efficiency calculated for optimized ODT and conventional directly compressed tablet were almost comparable, indicating free dissociation of the drug from the resinate. The bitter taste of DXM can be masked by binding with ion exchange resin and the resinate can be successfully formulated into oral disintegrating tablets. Dizajniranje i evaluacija oralnih raspadajućih tableta dekstrometorfan hidrobromida s maskiranim okusom Cilj rada bio je pripraviti raspadajuće tablete dekstrometorfan hidrobromida (DXM) za oralnu primjenu (ODT) prihvatljivog okusa s namjerom da se pomogne pacijentima svih dobnih skupina. Gorki okus ljekovite tvari maskiran je vezanjem lijeka na ionskoizmjenjivačku smolu. Proučavan je utjecaj veličine čestica smole na količinu ljekovite tvari koja se može na nju vezati, vrijeme raspadanja in vitro i in vivo, te oslobađanje lijeka in vitro. Količina vezanog lijeka značajno se povećava sa smanjenjem veličine čestica smole. DSC i XRPD studije pokazuju da prilikom vezanja kristalinični oblik lijeka prelazi u amorfni. Oslobađanje ljekovite tvari izračunato za optimizirane ODT i izravno komprimirane tablete vrlo je slično, što ukazuje na slobodno oslobađanje lijeka iz smole. Gorki okus DXM može se maskirati vezanjem ljekovite tvari na ionsko-izmjenjivačku smolu iz koje se mogu pripraviti raspadajuće tablete za oralnu primjenu.

Formulation and Characterization of Floating Gelucire Matrices of Metoprolol Succinate

The aim of the current investigation was to formulat e floating sustained-release matrices of metoprolol succinate using Gelucire 43/01 and Gelucire 44/14 by a melt-solidification technique. The in vitro and in vivo characteristics of the prepared matrices were evaluated. The in vitro drug release studies performed in 0.1 N HCl revealed a proportional increase in drug release pattern with increased concentration of Gelucire 44/14. Drug release data were analyzed by various mathematical models, and the mean dissolution time, Dissolution Efficiency, and similarity factor (f2) were determined in optimizing formulations. Differential scanning calorimetry and Fourier transform infrared spectroscopy showed no chemical interaction between drug and carriers studied. The in vitro floating characteristics of Gelucire matrices were greater than 12 h with good in vivo gastric retention. The results indicate that Gelucire 43/01 is an appropriate carrier for the development of sustained-release floating drug delivery systems and Gelucire 44/14, a highly hydrophilic and lipophilic balance (HLB) excipient, acts as release enhancer in the formulations studied.

Rapid, Selective and Rugged LCMS/MS Method Development and Validation for the Estimation of Clarithromycin in Dog Plasma

Abstract A new, simple, fast, sensitive and selective high performance liquid chromatography (HPLC) coupled with electrospray ionization tandem mass spectrometric method (LC-MS/MS) was developed and validated for the determination of clarithromycin in beagle dog plasma using imipramine as internal standard. The analyte was chromatographed under isocratic conditions on inertsil ODS 3 V (250X4.6 mm) 5μ column using mobile phase of 0.1% Formic acid: Methanol (15:85% v/v). The column temperature and flow rate was 40 ± 5°C and 1 ml/min respectively. The retention time for clarithromycin is within 1.52 min. Analysis was performed in the negative ionization mode using multiple reaction monitoring of the ion transitions at m/z 748.37/157.83 for clarithromycin and m/z 280.98/85.94 for internal standard, respectively. The validation was carried out over 9.922 - 4037.459 ng/ml of clarithromycin with the correlation coefficient of ≥ 0.9950. Method was validated for linearity, precision, accuracy, specificity, sensitivity, matrix effect, dilution integrity, ruggedness, reinjection reproducibility and stability. Clarithromycin was stable in stock solutions and in dog plasma samples under representative storage conditions. The present developed and validated method could be useful for the estimation of clarithromycin in beagle dog plasma.