Balkishen Razdan

Glibenclamide-loaded self-nanoemulsifying drug delivery system: development and characterization

Objective: To develop and characterize self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble drug, glibenclamide (GBD). Methods: Solubility of GBD was determined in various vehicles. Phase diagrams were constructed to identify efficient self-emulsification region using oils, surfactants, and cosurfactants in aqueous environment. Formulations were assessed for drug content, spectroscopic clarity, emulsification time, contact angle, zeta potential, particle size, and dissolution studies. On the basis of similarity and dissimilarity of particle size distribution, formulations were further characterized using principal component analysis and agglomerative hierarchy cluster analysis. Results: Among the formulations prepared and evaluated, optimized formulation showed mean particle size between 15.65 and 32.70 nm after 24 hour postdilution in various media. Dilution volume had no significant effect on particle size. Transmission electron microscopy of these formulations confirmed the spherical shape of globules with no signs of coalescence of globules and precipitation of drug. The relevance of difference in t50% and percent dissolution efficiency were evaluated statistically by two-way ANOVA. Infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction studies indicated compatibility between drug, oil, and surfactants. Conclusions: The results of this study indicate that the self-nanoemulsifying drug delivery system of GBD, owing to nanosize, has potential to enhance its absorption and without interaction or incompatibility between the ingredients.

Development and characterization of a lovastatin-loaded self-microemulsifying drug delivery system

The objective of the work was to develop, optimize and evaluate a self-microemulsifying drug delivery system of the poorly water soluble drug, lovastatin. Solubility of lovastatin was determined in various vehicles. Ternary phase diagrams were constructed to identify the efficient self-emulsification region using oils, surfactants, and co-surfactants in aqueous environment. Optimized formulations were assessed for drug content, spectroscopic clarity, emulsification time, contact angle, zeta potential, particle size and dissolution studies. Zeta potential was measured in absence and presence of oleylamine, a positive charge inducer. On the basis of similarity and dissimilarity of particle size distribution, formulations were characterized using principal component analysis and agglomerative hierarchy cluster analysis, the multivariate statistical analysis. Transmission electron microscopy of selected formulations (F5–F7) confirmed the spherical shape of globules with no signs of coalescence of globules and precipitation of drug, even after 24 h post dilution in distilled water. The relevance of differences in t50% and percentage dissolution efficiency was evaluated statistically by two-way ANOVA. Infrared spectroscopy, differential scanning calorimetric and x-ray diffraction studies indicated no incompatibility between drug, oil and surfactants. The results of this study indicate that the self-microemulsifying drug delivery system of lovastatin, owing to nanosize, has potential to enhance its absorption and without interaction or incompatibility between the ingredients.

Development and characterization of a carvedilol-loaded self-microemulsifying delivery system

The objective of the work was to develop, optimize, and evaluate a self-microemulsifying drug delivery system of the poorly water-soluble drug, carvedilol. Solubility of carvedilol was determined in various vehicles. Ternary and pseudo-ternary phase diagrams were constructed to indentify the efficient self-emulsification region using oils, surfactants, and co-surfactants in aqueous environment. Optimized formulations were assessed for drug content, spectroscopic clarity, emulsification time, contact angle, zeta potential, particle size, and dissolution studies. Zeta potential was measured in the absence and presence of oleylamine, a positive charge inducer. On the basis of similarity and dissimilarity of particle size distribution, formulations were characterized using PCA and AHCA, a multivariate statistical analysis. Decrease in t50% and increase in DE attributed to small globule size and eventually higher surface area. The relevance of differences in t50% and DE was evaluated statistically by two-way ANOVA. DRIFTS, DSC, and X-RD studies indicated no incompatibility between drug, oil, and surfactants. The results of this study indicate that the SMEDD formulations of carvedilol owing to nanosize have the potential to enhance its absorption, without interaction or incompatibility between the ingredients.

Atomic Force Microscopy, Transmission Electron Microscopy, and Photon Correlation Spectroscopy: Three Techniques for Rapid Characterization of Optimized Self-Nanoemulsiying Drug Delivery System of Glibenclamide, Carvedilol, and Lovastatin

This article looks at atomic force microscopy as an important aid to characterize the self-nanoemulsifying formulation of glibenclamide, lovastatin, and carvedilol in conjunction with other sophisticated technique, viz., transmission electron microscopy and photon correlation spectroscopy. Sizes obtained by processing the atomic force microscopy (AFM) image are comparable with those obtained from transmission electron microscope. Although in the present study, the mean particle size obtained from photon correlation spectroscopy does not correlate to the findings of atomic force microscopy and transmission electron microscopy, but the poly-disperse index values correlate well with the findings of AFM and transmission electron microscopy where uniform particle size was observed in aqueous dispersion of self-nanoemulsifying formulation of glibenclamide, lovastatin, and carvedilol.

Studies on azabicyclo systems: syntheses and spasmolytic activity of analogues of 9-methyl-3,9-diazabicyclo[4.2.1]nonane and 10-methyl-3,10-diazabicyclo[4.3.1]decane

Abstract The spasmolytic activity of the lactams, 9-methyl-3,9-diazabicyclo[4.2.1]nonan-4-one 1 and 10-methyl-3,10-diazabicyclo[4.3.1]decan-4-one 2 and their reduction products, 9-methyl-3,9-diazabicyclo[4.2.1]nonane 3 and 10-methyl-3,10-diazabicyclo[4.3.1]decane 4 are described. Syntheses and spasmolytic effects of new amides and sulfonamides of the amines 3 and 4 are also reported. 3 possessed specific anti-serotonin activity. Amides of 3 with aromatic acids resulted in specific anti-histaminic compounds, whereas amides of 4 with aliphatic acids showed spasmogenic activity. A number of amides and sulfonamides showed non-specific spasmolytic activity.

Evaluation of dosage forms. III: Studies on commercial acetaminophen tablet dosage forms

Abstract Dissolution-dialysis studies on commercial tablets of acetaminophen have been carried out in order to establish the applicability of this technique as a suitable in vitro method for the evaluation of acetaminophen dosage forms. While disintegration time or dissolution rate studies did not give a true indication of bioavailability, an excellent correlation was found between the dialysis rate constant (K) and the pharmacokinetic parameter AUC obtained from bioavailability studies on human volunteers.

Structural Transitions of Self-Nanoemulsifying Drug Delivery System of Glibenclamide, Carvedilol, and Lovastatin upon Progressive Aqueous Dilution

The dynamics of morphological transition in amphiphillic systems such as self-nanoemulsifying drug delivery system (SNEDDS) has become an increasingly active field of research in colloidal science. The present contribution deals with the morphological transition of selected optimized SNEDDS formulations of glibenclamide, carvedilol, and lovastatin on progressive aqueous dilution using transmission electron microscopy. The study emphasizes the structural aspects of the systems and stresses the effect of aqueous dilution under which the systems transform from water-in-oil (L2) phase into bicontinuous structure and, finally, in oil-in-water (L1) nanodroplets.

Evaluation of Dosage Forms. IV. Studies on Commercial Phenylbutazone Tablet Dosage Forms

In order to determine the feasibility of dissolution-dialysis as a suitable technique for in vitro evaluation, studies on commercial phenylbutazone tablets were carried out. Although disintegration time and dissolution parameters did not give a true indication of bioavailability, an excellent correlation was obtained between the dialysis rate constant (K) and various pharmacokinetic parameters obtained from bioavailability studies on human volunteers.

Plumbagin analogs-synthesis, characterization, and antitubercular activity

Considering the emerging problem of drug resistance in tuberculosis, there is an urgent need of development of new analogs that are useful in curing drug resistant tuberculosis. In India, tuberculosis continues to remain one of the most pressing health problems. India is the highest tuberculosis burden country in the world, accounting one fifth of global incidence - estimated 2.0-2.5 million cases annually. In 2011, approximately 8.7 million new cases of tuberculosis and 1.4 million people die from tuberculosis each year worldwide. Current antitubercular therapies are successful against normal tuberculosis but it is not suitable for drug resistant tuberculosis. In this study Plumbagin analogs, obtained from Plumbago zeylanica (Family-Plumbaginaceae), have been synthesized. Out of the various synthesized analogs, the antitubercular activity of compound a and b was evaluated using standard H37Rv and S, H, R, and E sensitive M tuberculosis strains using LRF assay method. Compound a showed strong activity against both standard H37Rv and S, H, R and E sensitive M. tuberculosis strains as compared to standard Rifampicin. The other compounds are proved to be more active against standard H37Rv and S, H, R and E sensitive M. tuberculosis strain as compared to Rifampicin.

Evaluation of dosage forms. VI. Studies of commercial oxyphenbutazone tablet dosage forms.

Dissolution-dialysis studies of commercial tablets of oxyphenbutazone were carried out to establish the applicability of this technique for the in vitro evaluation of oxyphenbutazone dosage form. While disintegration time and dissolution rate studies did not give a true indication of bioavailability, an excellent correlation was obtained between the dialysis rate constant K and the pharmacokinetic parameters AUC and Cmax.