Preparation of prospective plant oil derived micro-emulsion vehicles for drug delivery.

Biocompatible oil-in-water (o/w) micro-emulsions can be prospective drug delivery vehicles for their capability to solubilize lipophilic (oil soluble) drugs in the dispersed oil. Plant oils are considered suitable for such a purpose. In this study, we have attempted to examine the dispersion of corn, cottonseed, clove, orange and peppermint oils, as well as isopropyl myristate (IPM) in water continuum in presence of surfactants Tween-20, Brij-30 and Brij-92 and co-surfactants ethanol (EtOH) and isopropyl alcohol (iPrOH). Both ternary (oil/surfactant/water) and psedoternary (oil/surfactant + co-surfactant/water) phase diagrams were constructed. The ternary systems produced larger micro-emulsion forming zones than the psedo-ternary systems. The combinations peppermint oil/iPrOH/water, IPM/iPrOH/water and 1:1 (v/v) peppermint oil + IPM/iPrOH/water were found to form fair proportion of single-phase surfactant-less micro-emulsion. The surfactant-aided ternary systems produced larger clear microemulsion zones, compared to pseudo-ternary systems, while the behaviour of surfactant-less systems was intermediate. The prepared systems had shelf life of 1 year and they withstood temperature variations in the range of 4-40 degrees C.

Interaction of sodium dehydrocholate and sodium cholate with polyvinyl pyrrolidone in aqueous medium.

The results of interaction of the bile salts sodium dehydrocholate (NaDHC) and sodium cholate (NaC) with the water soluble polymer polyvinyl pyrrolidone (PVP) studied by the methods of conductance, surface tension, viscosity and calorimetry are reported. Both of the bile salts exhibited PVP influenced self-aggregation. While NaC showed expected surface tension behaviour, NaDHC exhibited anomalous behaviour. The minimum interfacial area per molecule of the bile salt, the maximum interfacial adsorption, the free energy of micellization and the free energy of interfacial adsorption are presented for NaC. This information was not obtained for NaDHC because of its anomalous surface tension behaviour. The bile-salt-adhered PVP exhibited polyelectrolyte behaviour at PVP concentrations < 0.25 g dl-1. The enthalpy of interaction of NaC with PVP had a maximum at 0.25 mole dm-3 (delta Hi = +180 cal/mole); NaDHC produced too little heat to be detected by the calorimeter.

Biological microemulsions V: mutual mixing of oils, amphiphiles and water in ternary and quaternary combinations.

The mixing behaviour of plant oils (ricebran, saffola and clove) with water in presence of amphiphiles (Triton X-100, Tween-60, Aerosol OT, Igepal, Na-oleate, ethanol and cinnamic alcohol) in various ternary and quaternary combinations has been studied. The phase behaviour at different mass proportions and temperature has been investigated in the absence and presence of additives such as NaCl, glucose, urea and cholesterol. Of all the combinations studied, those with ethanol plus sodium oleate as amphiphile have shown maximum extent of single phase microemulsion formation. The presence of urea in the aqueous medium has further increased the monophasic extent whereas NaCl has decreased it. Cholesterol in oil and glucose in water have apparently shown inert effects. The effects of the additives on the formation of biphasic or triphasic formulations, on the other hand, have been found to be distinct and well-dependent on [H2O]/[amphiphile] mole ratio and temperature. Spectral measurements of I3- in the aqueous micropool in microemulsion of clove oil/(ethanol + Na-oleate)/water have shown the microenvironment to be physicochemically different from bulk water.

Activity of alkaline phosphatase in water-in-oil microemulsions containing vegetable oil.

The hydrolysis of p-nitrophenyl phosphate by the enzyme alkaline phosphatase has been studied in vegetable oil containing water-in-oil (W/O) microemulsions of six different compositions at four different (water)/(surfactant) mole ratios of 10, 17.6, 24.7 and 37. The vegetable oils used are ricebran oil (RO) and clove oil (CO) and the amphiphiles used are Aerosol OT (AOT), cinnamic alcohol (CA) and Tween-20 (T-20). The hydrolytic process does not follow conventional Michaelis Menten equation normally observed for enzymatic process. In the water/vegetable oil microemulsions, the enzyme seems to lose its activity when AOT is the amphiphile. The amount of p-nitrophenol generated as a result of hydrolysis is independent of the presence of the enzyme. With Tween-20 as the amphiphile, the microemulsion produces an initial retarding effect which ultimately gets appreciably compensated.

Biological microemulsions: Part IV--Phase behaviour and dynamics of microemulsions prepared with vegetable oils mixed with aerosol-OT, cinnamic alcohol and water.

Microemulsification of vegetable oils (ricebran, saffola, soyabean, sesame, palm and linseed) with water using aerosol-OT and cinnamic alcohol as mixed amphiphiles was studied. The biological microemulsions formed covered on the average approximately 27% of single phase area in the triangular phase diagram. The multiphasic zone for saffola was studied in detail, two- and three-phase zones were identified with patches of thick gel. The effect of temperature on the multiphase formation in the range 29-55 degrees C was also studied. The formation of multiphase and their proportions found to depend on the type of oil. The biological microemulsions at reasonable water/AOT mole ratio showed moderate increase in conductance with temperature. The viscosity of the microemulsions was high. Of the studied systems (sesame, saffola and ricebran) the viscosity of the first two decreased with the rate of shear whereas that of ricebran increased. When cinnamic alcohol was used as the oil, the trend of viscosity was similar to that of sesame and saffola.

Interaction of amino acids and gelatin with urea.

The pH titration of nine amino acids (glycine, proline, valine, serine, glutamine, tryptophan, arginine, histidine and aspartic acid) in presence of urea in the concentration range 1-8 mole dm-3 has been performed. The results support suppression of the first dissociation constant (K1) of the amino acids and acceptance of H+ ions by the amide forming uronium ion (UH+). The second dissociation constant (K2) of the amino acids is affected relatively weakly by urea. Quantitative evaluation of different species existing in solution and the degree of dissociation of the acids as well as the degree of binding of H+ ion to the amide have been made. It has been found that the polarity of the aqueous-urea medium does not straight forwardly correlate with the altered pK1 of the amino acids. Urea can also affect the pH-titration behaviour of gelatin with an increase of the intrinsic pK of the acidic groups of the protein by 0.45 unit.

Biological microemulsions: Part III--The formation characteristics and transport properties of saffola-aerosol OT-hexylamine-water system.

The results of formation, phase behaviour and physical properties of biological microemulsions prepared from saffola/AOT/hexylamine/water in presence of different additives, viz. cholesterol, crown ether, urea and brine, are presented. It has been found that the additives and temperature have striking effects; mono-, bi- and triphasic solutions interchanging proportions among themselves. The conduction of microemulsion at different [Water/AOT] ratios (w = 9,10,14,18,20,39 and 45) has shown conspicuous dependence on temperature with a significant degree of percolation, whereas the dependence of viscosity on temperature has shown normal declining trend with temperature. A maximum in viscosity with respect to its variation with amount of water has been observed. The Walden product (lambda eta) has evidenced noncompensation of ion transport by conduction with the viscosity of the medium. The activation energies evaluated for conduction (delta E*cond) and viscosity (delta E*vis) are systematic except at [Water/AOT] ratio, w = 20. The additives cholesterol, crown ether and their mixture have shown a decreasing effect on the delta E*cond for percolation, whereas delta E*vis has increased in their presence. The bicontinuous microemulsion has the prospect for use as liquid membrane.

Thermodynamics of water-induced precipitation of cholesterol and its acetate, benzoate and stearate derivatives dissolved in 1,4-dioxane and 2-propanol.

The energetics of the precipitation process depended on the solute-solvent combination and the enthalpy and entropy of precipitation compensated each other. The partial molal volumes of the lipids in both the solvents were greater than the anhydrous molar volumes, except for cholesterol in 1,4-dioxane and cholesteryl acetate in 2-propanol where the order was reverse. While the partial molal compressibilities of all the solutes studied were negative in 1,4-dioxane, those of cholesterol and cholesteryl acetate in 2-propanol were, respectively, negative and positive. The negative values were supported by considerable solvation of the solutes, particularly in 1,4-dioxane.

Water-induced precipitation of cholesterol dissolved in organic solvents in the absence and presence of surfactants and salts.

The precipitation of cholesterol dissolved in organic solvents, viz. methanol, ethanol, n-propanol, isopropanol, acetone and 1,4-dioxane, by the addition of water has been studied. The effects of the solvents towards the precipitation follow the order: methanol greater than ethanol greater than acetone greater than dioxane greater than n-propanol greater than iso-propanol, the solvent dioxane however exhibits a change in the order at higher concentration. Additives like Triton X-100, sodium cholate, sodium deoxycholate, sodium dehydro cholate, sodium salicylate and sodium chloride have some protective action against precipitation, the maximum protection being that of Triton X-100. The additives have shown better protective action in propanols and dioxane than in methanol, ethanol and acetone. Analysis of solvent composition and dielectric constant has revealed specific solvent effects on the water-induced precipitation of cholesterol. Thermodynamic analysis of the precipitation phenomenon and the unique role of solvent structure on cholesterol precipitation has been discussed.

Model biological microemulsions: Part I--Phase behaviour and physicochemical properties of cholesteryl benzoate and sodium deoxycholate contained microemulsions.

Phase behaviour and some physicochemical properties of cholesteryl benzoate-contained microemulsions of xylene and heptane with water using sodium deoxycholate and butan-1-ol as surfactant and co-surfactant respectively have been studied. While the microemulsion area of xylene depends insignificantly on the surfactant/co-surfactant ratio, that of heptane shows appreciable dependence. At surfactant + co-surfactant percentage of 50 or above, both the systems become oil continuous. With respect to time and temperature, the microemulsion systems have been found to be very stable. At low percentage of water, the xylene system is considerably viscous; that of heptane is less viscous but shows viscosity maximum at 45% water. Cholesterol in xylene has given greater viscosity than cholesteryl benzoate. The equivalent conductance of both the systems increase with increasing water content and the values are comparable. Unlike normal electrolyte solutions, the products of equivalent conductance and viscosity (the Walden product) sharply rise with increased water content, which suggests a special mechanism of conduction via 'channel' formation. The overall rigidity of the microemulsions is suggested by their lower specific volumes and compressibilities at all compositions. The excess specific volumes and excess compressibilities at different percentages of water are presented.