Sylvan G. Frank

In vitro release of lidocaine from pluronic F-127 gels

Abstract The release of lidocaine from aqueous, crystal clear and colorless gels of Pluronic F-127 (a polyoxyethylene-polyoxypropylene surface-active block polymer) has been studied in an in vitro release model which did not utilize a membrane. Pluronic F-127 forms micelles in aqueous systems and the gels are believed to be viscous isotropic liquid crystals. Due to their reverse thermal gelation behavior, good solubilization capacity, optical properties and low toxicity, they appear to have potential application as topical drug delivery systems. It has been found that the rate of lidocaine release was inversely proportional to its concentration, the concentration of Pluronic F-127 and electrolyte concentration (sodium chloride). Release of lidocaine was maximal at pH values close to its pK a ; however, release of the more water-soluble benzocaine (included for comparison purposes) was relatively pH-independent over the pH range studied. Since the apparent diffusion coefficient of lidocaine increased with increasing temperature, in spite of increasing macro-viscosity of the gel, it is apparent that drug is released by diffusion through the extramicellar aqueous channels of the gel matrix. Hence, the rate of drug release was determined by the micro-viscosity of the extramicellar fluid, the dimensions of the aqueous channels, and the equilibrium relationship of drug between the micelles and the external aqueous phase.

MICROCRYSTALLINE CELLULOSE STABILIZEDEMULSIONS

ABSTRACT Miorocrystalline cellulose stabilized emulsions (o/w) were evaluated by means of brightfield and polarized light microscopy, freeze-etch electron microscopy, droplet size analyses and rheologic measurements. These studies indicated that miorocrystalline cellulose (Avicel RC591 ) forms a network around emulsified oil droplets. This structure provides a mechanical barrier at the o/w interface which stabilizes the emulsion without the necessity for decreasing interfacial tension, as in conventional surfactant-stabilized emulsions. Rheologic studies indicated that emulsions containing Avicel RC591 had a considerable degree of thlxotropy which contributed to their stability. When Tween 80 was incorporated in this system, oil droplets coalesced indicating that the stability of the emulsion was affected adversely.

MULTIPLE EMULSIONS STABILIZED BY COLLOIDAL MICROGRYSTALLINE CELLULOSE

ABSTRACT Multiple emulsions stabilized by colloidal microcrystalline cellulose (CMCC, Avicel RC591) at the w/o and o/w interfaces, and by the addition of Span 80 or Span 85 at the w/o interface, were studied by means of brightfield microscopy, freeze-etch electron microscopy, droplet size distribution analysis and rheologic measurements. Stable multiple emulsions were prepared by incorporation of sodium chloride in the innermost aqueous phase, thereby creating an osmotic gradient preventing loss of the inner aqueous phase to the external aqueous phase. Freeze-etch electron microscopy of the multiple emulsions indicated the presence of a network of microcrystalline cellulose at the outer o/w interface. It may be assumed that the surfactant directly stabilized the w/o interface by adsorption at the interface, as well as indirectly by facilitating wetting of the microcrystalline cellulose by the oil. From rheologic measurements, the existence of a three-dimensional network in the external aqueous phase was i...

Interaction of lidocaine and lidocaine-HCl with the liquid crystal structure of topical preparations

Abstract The interaction of lidocaine and lidocaine-HCl with liquid crystal structures of preparations suitable for topical use was studied by polarized light and transmission electron microscopy and small angle X-ray diffraction. Furthermore, in vitro release studies were performed to determine if possible differences in the microstructure of the systems may be recognized by different release patterns. It has been found that both lidocaine and lidocaine-HCl participate in the liquid crystalline structure which primarily consists of hydrated surfactant bilayers in a system consisting of soyasterol-PEG-ether, water and drug. Completely lipophilic components like paraffin, however, are not built into the microstructure as individual molecules but are dispersed as droplets in the system. The incorporation of 1% drug results in a slight increase of the interlayer spacings as measured by X-ray. From the release experiments, it can be concluded that not only the method of preparation but also the amount of the ratio of water/(water + surfactant), the presence of paraffin, and the form of the drug incorporated, may determine the release. In case of lidocaine base, the apparent diffusion coefficients increase with increasing amount of water. The diffusion of the drug through the system is independent of the method of preparing the systems. On the other hand, incorporating lidocaine after preparation of the vehicle itself leads to systems containing a surplus of undissolved drug, while melting lidocaine together with the surfactant before adding water and forming lamellar liquid crystals results in complete solubilization of lidocaine. Because of the higher solubility of lidocaine-HCl salt the systems prepared according to both methods contain dissolved drug. However, from the release profiles can be inferred, that the location in the liquid crystalline structure of the salt is different from that of the free base. Adding the drug after preparation of the vehicle did not permit the drug to enter the water containing liquid crystalline bilayers. The drug is loosely bound to the surface of vesicular liquid crystal structures and hence is easily released. In situ preparation of drug containing liquid crystals leads to entrapment of the salt within the aqueous region of the liquid crystal lamellae. The release of lidocaine-HCl from this type of microstructure is slow because the ability of the salt to penetrate the more lipophilic regions of the bilayers is low. The different options described for a drug participating in the microstructure of these liquid crystal systems which can be applied to the skin show the important role, knowing about the interactions between the various components, because they may affect the release of drug and the subsequent effect on topical therapy.

Viscosity and colloidal properties of concentrated crude oil-in-water emulsions

Abstract A significant fraction of petroleum reserves in the United States, Venezuela, and Canada are heavy crudes. Water continuous emulsions can be used to transport these highly viscous crudes in pipelines. Many crudes form emulsions with alkaline water due to saponification of natural acids. The viscosity of these anionic emulsions varies with continuous phase ionic strength due to electroviscous effects. Experimental studies were undertaken to determine the effect of NaOH and NaCl concentration on the viscosity, particle diameter, and zeta potential of emulsions of a Boscan heavy crude from Venezuela and a Cold Lake heavy crude from Canada. Oil-in-water emulsions could be formed only for a narrow range of NaOH concentrations. This range was approximately 0.010 to 0.080 mmole/g oil for the Boscan crude and 0.010 to 0.050 mmole/g for the Cold Lake crude. The properties of emulsions exhibited extrema at NaOH concentrations approximately equivalent to the total acid number (TAN) of each crude. This occurred because the maximum surfactant concentration obtainable from the natural acids was reached at the TAN equivalence point. High shear rate viscosity, stability, and zeta potential increased with NaOH addition below this concentration, while particle diameter decreased. Addition of excess NaOH or of NaCl above the equivalence point caused decreases in viscosity and increases in particle diameter at equivalent total sodium ion concentrations. For a given crude, variation of emulsion viscosity with electroviscous effects could be explained by zeta potential and particle diameter changes. However, large differences in the magnitude of electroviscous effects for different crudes were observed. These differences could not be explained by relative zeta potentials, particle diameters, or TANs. Also, electroviscous effects and the stability of emulsions to aging were modified by addition of tall oil. Saponifiable acids present in tall oil differ from those found in crude oils. These two observations indicate the importance of specific surfactant chemistry on emulsion viscosity and electroviscous effects.

Drug release from emulsions stabilized by colloidal microcrystalline cellulose

ABSTRACT Drug release from water-in oil-in water (w/o/w)multiple emulsions stabilized with colloidal microcrystal-line cellulose and various surface-active agents has been studied in vitro. Lidocaine hydrochloride and lidocaine base were used as model drugs for these studies. Drug concentrations were measured by HPLC, and effective diffusion coefficients were determined.

Studies of Water-Continuous Emulsions of Heavy Crude Oils Prepared by Alkali Treatment

Pumping of heavy crudes as concentrated oil-in-water (O/W) emulsions may be a feasible pipeline transport scheme for viscous crudes. Many crude oils can be emulsified by treatment with alkali without the addition of expensive surfactants. In experimental studies of seven crudes, stable emulsions could be formed with four by alkali treatment; two could not be emulsified; and one formed unstable emulsions. High shear viscosity, particle size, and stability measurements on 60% emulsions formed with various amounts of alkali are reported. High shear viscosities below 100 mPa . s (100 cp) at 25/sup 0/C (77/sup 0/F) indicate that concentrated emulsions of some crudes can be transported in pipelines at concentrations of 60% and higher.

CONCENTRATED VISCOUS CRUDE OIL-IN-WATER EMULSIONS FOR PIPELINE TRANSPORT

The need to utilize viscous crude oils will increase in the next decade. One means to facilitate pumping of heavy crudes in pipelines is to transport them as concentrated oil-in-water emulsions. Stable emulsions could be prepared by alkali treatment with four of seven viscous crudes studied. Surfactants are formed by reaction of natural acids in the crude with alkali. At crude volume fractions of 60%, emulsion apparent viscosity was lowered as much as 10,000 times. Viscosities of crude emulsions formed by alkali treatment varied with the nature of the crude and with the ratio of base added to the TAN of the crude. Emulsion viscosities and particle diameters reach extrema close to the equivalence point. The addition of tall oil enhanced the emulsification ability of some of the crudes with alkali treatment, but one crude required non-ionic surfactant to form an emulsion.

Ultraviolet and nuclear magnetic resonance studies of the solubilization of chlorzoxazone by alkyltrimethylammonium halides

Abstract From comparisons of the spectra of chlorzoxazone before and after solubilization in solutions of Tween 80, sodium lauryl sulfate, and cetyltrimethylammonium bromide (CTAB), the most significant changes were found for the cationic CTAB. Subsequent studies of the interaction of chlorzoxazone with CTAB indicated that the quaternary ammonium group induces the ionization of chlorzoxazone from its nonionic keto form to its ionized enolate form. From changes in the UV absorbance of chlorzoxazone after solubilization in solutions of CTAB, the binding constant of chlorzoxazone with the CTAB micelles (5.51 × 10 4 M −1 ) and the approximate number of binding sites (8) were calculated by Sepulvedas method, modified to include the critical micelle concentration. Furthermore, NMR studies of the more soluble chlorzoxazone-dodecyltrimethylammonium chloride (DTAC) systems indicated that chlorzoxazone was located in the palisade layer of the DTAC micelles with its carbonyl oxygen close to the surface and chlorine atom facing inward toward the nonpolar core of the micelles.

FORMATION OF OIL IN GLYCEROIVWATER EMULSIONS: EFFECT OF SURFACTANT ETHYLENE OXIDE CONTENT

ABSTRACT Oil-in-glycerol/water emulsions at various ratios of water to glycerol in the external phase were prepared with polyoxyethylated octylphenols and light mineral oil. As the water concentration in the external phase decreased, oil droplet size decreased down to a minimum size beyond which oil separation occurred. Also, the cloud points of various surfactants were depressed toward room temperature as the water content of the glycerol/water mixtures decreased. It was possible therefore to correlate the concentration of water needed for formation of the smallest droplets to the concentration of water needed for depression of the cloud point of each surfactant to room temperature.