Prediction and elucidation of factors affecting solubilisation of imatinib mesylate in lipids.

The physico-chemical properties of lipids influencing the solubilisation of imatinib mesylate (IM) in lipid matrix were evaluated and a statistical model to predict the same has been derived in the present study. After experimental quantification of IM solubility in various lipids, Hansen Hildebrand's total solubility parameters were calculated in order to study the role of various forces connected to lipid-drug interaction. To develop a relationship between the various descriptors of the lipids and experimental solubility of IM in lipids (% w/w), quantitative structure-solubility relationship (QSSR) was used. To generate equations that can predict the solubility of IM in lipids (%w/w), multiple linear regression was used. Amongst the various lipids tested, glyceryl monostearate and behenic acid solubilised the highest (6.19 ± 0.22%) and lowest (0.01 ± 0.01%) amounts of IM respectively. Our results suggested that alkyl chain length, polarity of the lipids, index of cohesive interaction in solids, estimated number of hydrogen bonds that would be accepted by the solute from water molecules in an aqueous solution, estimated number of hydrogen bonds that would be donated by the solute to water molecules in an aqueous solution and solvent accessible surface area collectively play a significant role in solubilising IM in the lipids. The equation developed could predict the solubility of IM in lipids with good accuracy (R2pred = 0.912).

Quillaja saponin: A prospective emulsifier for the preparation of solid lipid nanoparticles.

Quillaja saponin (QS) is a non-ionic amphiphilic surfactant of natural origin. In the present study, we evaluated its potential to form solid lipid nanoparticles (SLNs) in the presence of stearic acid (SA) as a lipid carrier and imatinib mesylate (IM) as a model drug. IM loaded solid lipid nanoparticles (IMSLNs) were prepared using the hot homogenisation method. Characterisation of IMSLNs revealed that they were quasi-spherical in shape, neutrally charged and 143.5-641.9nm in size. Haemolysis, a toxicity issue of QS was not observed in SLNs. Comparative in vitro cytotoxicity analyses performed in human breast cancer cell line MCF7 revealed that IMSLNs were more toxic than IM. On the other hand, in vitro viability studies in the RAW264.7 cell line did not show any sign of toxicity by IMSLNs. Our results indicate that QS hold great potential in nano drug delivery as an emulsifier.

A brief perspective on the diverging theories of lymphatic targeting with colloids.

For targeted delivery of colloids to the lymphatic system, the colloids should efficiently reach and remain in the lymphatics for a considerable period of time. As per the current knowledge, diffusion and phagocytosis are the two mechanisms through which colloids reach the lymphatic system. Several parameters including particle size and charge have been shown to affect the direct uptake of colloids by the lymphatic system. Although many researchers attached ligands on the surface of colloids to promote phagocytosis-mediated lymphatic delivery, another school of thought suggests avoidance of phagocytosis by use of carriers like polyethylene glycol (PEG)ylated colloids to impart stealth attributes and evade phagocytosis. In this perspective, we weigh up the paradoxical theories and approaches available in the literature to draw conclusions on the conditions favorable for achieving efficient lymphatic targeting of colloids.

Self nanoemulsifying drug delivery system (SNEDDS) of rosuvastatin calcium: design, formulation, bioavailability and pharmacokinetic evaluation.

The aim of the present study is to improve solubility and bioavailability of Rosuvastatin calcium using self nanoemulsifying drug delivery system (SNEDDS). Self emulsifying property of various oils including essential oils was evaluated with suitable surfactants and co-surfactants. Ternary phase diagrams were constructed based on Rosuvastatin calcium solubility analysis for optimizing the system. The prepared formulations were evaluated for self emulsifying time, robustness to dilution, droplet size determination and zeta potential analysis. The system was found to be robust in different pH media and dilution volume. The globule size of the optimized system was less than 200nm which could be an acceptable nanoemulsion size range. The zeta potential of the selected CN 7 SNEDDS formulation (cinnamon oil 30%; labrasol 60%; Capmul MCM C8 10%) was -29.5±0.63 with an average particle size distribution of 122nm. In vitro drug release studies showed remarkable increase in dissolution of CN7 SNEDDS compared to marketed formulation. In house developed HPLC method for determination of Rosuvastatin calcium in rat plasma was used in the bioavailability and pharmacokinetic evaluation. The relative bioavailability of self nanoemulsified formulation showed an enhanced bioavailability of 2.45 times greater than that of drug in suspension. The obtained plasma drug concentration data was processed with PKSolver 2.0 and it was best fit into the one compartment model.

An in vitro and in vivo investigation into the suitability of bacterially triggered delivery system for colon targeting.

The colon specific drug delivery systems based on polysaccharides; locust bean gum and chitosan in the ratio of 2 : 3, 3 : 2 and 4 : 1 were evaluated using in vitro and in vivo methods. The in vitro studies in pH 6.8 phosphate buffer containing 2% w/v rat caecal contents showed that the cumulative percentage release of mesalazine after 26 h were 31.25+/-0.56, 46.25+/-0.96, 97.5+/-0.26 (mean+/-S.D.), respectively. The in vivo studies conducted in nine healthy male human volunteers for the various formulations revealed that, the drug release was initiated only after 5 h (i.e.) transit time of small intestine and the bioavailability (AUC(0-->t*)) of the drug was found to be 85.24+/-0.10, 196.08+/-0.12, 498.62+/-0.10 microg x h/ml 26 (mean+/-S.D.), respectively. These studies on the polysaccharides demonstrated that the combination of locust bean gum and chitosan as a coating material proved capable of protecting the core tablet containing mesalazine during the condition mimicking mouth to colon transit. In particular, the formulation containing locust bean gum and chitosan in the ratio of 4 : 1 held a better dissolution profile, higher bioavailability and hence a potential carrier for drug targeting to colon.