Room temperature ionic liquids and their mixtures: potential pharmaceutical solvents.

Room temperature ionic liquids (RTILs) are organic salts which are liquids at ambient temperature. Composed of relatively large asymmetric organic cations and inorganic or organic anions, they have generated interest as 'green' solvents. Here we report on the solvency of alkyl imidazolium salts (PF(6)(-)Br(-)Cl(-)) for poorly water-soluble model drugs, albendazole and danazol, indicating their potential application as pharmaceutical solvents/cosolvents. The solubility of albendazole, for example, is increased by more than 10,000 times by 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim]PF(6)(-)). Ionic liquids can be water-miscible or water-immiscible. The aqueous miscibility of a poorly water-miscible RTIL such as of [bmim]PF(6)(-) can be improved by the inclusion of a second more miscible RTIL (e.g. 1-hexyl-3-methylimidazolium bromide ([hmim]Br(-))). The extent of improvement in water miscibility was found to correlate with the hydrophilicity of the second RTIL. This ability to modulate RTILs' aqueous miscibility increases their usefulness as pharmaceutical solvents.

Non-aqueous emulsions: hydrocarbon-formamide systems.

There are few reports in the literature on formulation of non-aqueous emulsions. This study was designed to evaluate some design criteria for such systems. Formamide is the closest polar solvent that has the ability to replace water in emulsification when employing established non-ionic surfactants as stabilisers. For the majority of studies, linear alkanes (C6-C16) were dispersed in formamide as the continuous phase were stabilised with polysorbate 20. Initial studies involved gentle emulsification and observing mean globule size. The mean globule size varied in a non-linear fashion with alkyl chain length, the minimum being between C10 and C12. Sonication for 30 s led to smaller differences in the mean globule size. The effect of various parameters such as surfactant concentration and solvophilicity of the surfactant was observed. The surface activities of polysorbate 20, 40, 60 and 80 in formamide and critical micellar concentrations were determined. The latter were several orders of magnitude higher in formamide than in water, and the areas per molecule larger. The addition of water to the dodecane formamide systems did not destabilise the emulsion. Release of the model drug dehydroepiandrosterone from dodecane in formamide emulsions was studied in distilled water, the rate of release being dependent on the volume fraction of dodecane.

Synthesis and characterisation of palymitoyl propanolol hydrochloride auto-lymphotrophs for oral administration.

Self-associating supramolecular organisation of molecules above critical micellar concentrations (c.m.c.) offers enormous potentials in figuring distinguished behaviour both within formulations as well as in the bioenvironment. The present study deals with the enhancement of the oral bioavailability of propranolol HCl by synthesising the amphiphathic prodrug, which tends to aggregate in supramolecular orientations. The palmitoyl derivative of propranolol HCl was prepared by esterification of the secondary OH group. The prepared palmitoyl propranolol HCl (PPH) was characterised for its structure by IR and NMR spectroscopy as well as its physicochemical properties, hydrolysis profile and interfacial behaviour. The degree of hydrolysis as well as the aminolysis of aggregated and molecular PPH was monitored as a function of varying pH. The aminolysis could be effectively ablated in the case of the aggregated form of PPH. The in vivo bioavailability was determined by calculating the area under the curve in the blood plasma profile after oral administration of PPH in the form of a liquid crystalline dispersion and molecular dispersion. The possible mechanism operating for the enhancement of oral bioavailability was established as lymphatic transportation.

Development and characterisation of supramolecular autovectoring system for selective drug delivery.

Supramolecules since ages have been characterised as self-associating systems emanating the properties directly related to the mode of molecular association. Similar to supramolecules, liquid crystals may also be considered as an associated system. The liquid crystals are defined as the state of matter with the characterstic order of the crystal and the mobility of liquid. The system has been compared to the transporting form of cholesterol in body. The present study reports autovectoring potentials of the drug liquid crystals using diclofenac diethylammonium (DD) as a model. The drug based liquid crystals of DD were prepared employing temperature induced transformation of isotropic form to the liquid crystal form. The prepared liquid crystal systems were incubated with 1% phosphatidylcholine in order to stabilise the surface and restrict it into the liquid crystalline state. The system was characterised for viscosity variation, X-ray diffraction pattern, partitioning behaviour and in vitro diffusion profile. In vivo vectorising potential of the developed system was evaluated using rats as test animal and studying for the organ level distribution and drug compartmentalisation. The system exhibited satisfactory vecterisation as significant amount of administered dose was localised selectively in liver.

Discoidal niosome based controlled ocular delivery of timolol maleate.

Non-ionic surface active agents based discoidal vesicles (discomes) bearing timolol maleate were prepared. Niosomes were incorporated with Solulan C24 in order to effect vesicle to discome transition. The discomes were relatively large in size, 12-60 microm. They were found to entrap a relatively high quantity of timolol maleate. The prepared system characterized for size, shape and drug release profile in vitro. They were found to release the contents following biphasic profile particularly in the case where the drug was loaded using a pH gradient technique. The prepared system could produce or sustain a suitable activity profile upon administration into the ocular cavity; however, systemic absorption was minimized to a negliable level. The discomes were found to be promising and of potential for controlled ocular administration of water-soluble drugs.

Lipoproteins: their potential as endogenous target oriented novel drug delivery system.

Targeting of drugs to specific cellular sites is a major area of interest now a day. Various carrier systems, viz, liposomes, resealed erythrocytes, niosomes, immunomodulated nanospheres, etc. have been reported. A newer class of carrier system based on endogenous origin has been identified as lipoproteins. The present review discusses the classification, biological fate and targeting potentials of such system when the drug is encapsulated. Furthermore their is a brief discussion about the approaches utilised for their more specific targeting (acyloglycoprotein receptor etc.). Some of the observed drawbacks of such systems could be combated with the use of synthetically prepared lipoproteins named as SMBV (supramolecular biovectors) have also been discussed. Various biomedical potential of these lipoproteins in the delivery of drug to neoplastic cell lines, viral and parasitic infections in liver have also been highlighted.