The influence of HLB on the encapsulation of oils by complex coacervation

Abstract

Microcapsules are used for the formulation of drug controlled release and drug targeting dosage forms. Encapsulated hydrophobic drugs are often applied as their solutions in plant oils. The uptake of the oils in the complex coacervate microcapsules can be improved by the addition of surfactants. In this study, soybean, olive and peanut oils were chosen as the representatives of plant oils. The well characterized complex coacervation of gelatin and acacia has been used to produce the microcapsules. The amount of encapsulated oil has been determined gravimetrically. The encapsulation of the oils was high (75–80%). When the surfactants with HLB values from 1.8 to 6.7 were used, the amount of encapsulated oil was high (65–85%). A significant decrease of the oil content in the microcapsules was found when Tween 61 with HLB = 9.6 had been added into the mixture. No oil was found inside the microcapsules from the coacervate emulsion mixture containing Tween 81 (HLB = 10) and Tween 80 (HLB = 15), respectively. The results of the experiment confirm the dependence of hydrophobic substance encapsulation on the HLB published recently for Squalan     

The effect of sodium lauryl sulphate, cetrimide and polysorbate 20 surfactants on complex coacervate volume and droplet size

The effects of sodium lauryl sulphate (SLS), cetrimide and polysorbate 20 surfactants at concentrations below, at and above their critical micelle concentration (CMC) on the complex coacervation of varying concentrations of gelatin and acacia have been described. The overall effect of increasing concentration of SLS was to reduce the weight of coacervate formed. The addition of increasing concentrations of cetrimide produced an increase in the weight of coacervate. The two lowest concentrations of polysorbate 20 produced an increase in coacervate weight while the highest concentration, above the CMC, reduced the coacervate weight. These effects have been explained in terms of shielding of electrostatic attractions between gelatin and acacia polyions by adsorption of ionic and non-ionic surfactant molecules onto the polyions. The addition of surfactants influenced the size distribution of the coacervate droplets that were produced. It is believed that the reduction in interfacial tension by the aggregation of surfactant molecules at the coacervate-equilibrium liquid interface permitted the formation of smaller coacervate droplets.     

Some preparative variables influencing the properties of W/O/W multiple emulsions

Abstract

Water-in-oil-in-water multiple emulsions of chloroquine diphosphate were prepared, using olive oil, arachis oil, Span 80, gelatin, acacia and Tween 80. Emulsifiers were employed individually or in combination. An attempt was made to correlate preparative variables with stability and drug release of multiple emulsions of roughly comparative particle size. When the emulsions were satisfactorily stabilized by the optimum blend of surfactants the rate of release varied with the nature and/or combination of emulsifiers employed. The possible effects of phase-inversion temperature, spontaneous emulsification and liquid crystal stabilization on the systems have been discussed. The mechanism probably involved complex interfacial adsorption and hydrodynamic phenomena in the presence of natural oils, co-surfactants and natural stabilizers of individual HLB number, particularly when acacia is present in the system. This could be attributed to the existence of protein in some species of acacia, since there are about 130 species of acacia, the gummy exudations of which are considered official in compendia. The protein content could be a reasonable additional specification for acacia as an emulsifier.     

Spontaneous Formation of Small Sized Albumin/acacia Coacervate Particles

Abstract— Microgel coacervate particles form spontaneously on mixing aqueous solutions of oppositely charged albumin and acacia, under specific conditions of pH, ionic strength, and polyion concentration, close to but not at the optimum conditions for maximum coacervate yield. The mean particle diameter of these coacervate particles is approximately 6 μm when suspended in aqueous media, as determined by HIAC/Royco particle analysis. The geometric standard deviation of the particles falls in the range 1·2–1·9 μm. The particle size was not dependent on the method of emulsification of the coacervate in the equilibrium phase, or on the stirring speed applied during the manufacturing process. The microgel particles were stable on storage, for periods up to forty-six days, without the addition of a chemical cross-linking agent, or the application of heat. Stability was measured with respect to the change in particle size of samples stored at different temperatures. The non-cross-linked microcapsules were also shown to be stable on pH change, to pH values outside the coacervation pH range. At the optimum conditions for maximum coacervate yield the albumin/acacia system formed a very viscous coacervate phase, which was unsuitable for microcapsule preparation. The Theological properties of albumin/acacia and gelatin/acacia complex coacervates optimized for maximum coacervate yield were compared. The albumin/acacia coacervate was shown to be three orders of magnitude more viscous than the gelatin/acacia system.     

Assessment of the percutaneous penetration of indomethacin from soybean oil microemulsion: effects of the HLB value of mixed surfactants

The objective of this study was to evaluate the influence of the ratios or the hydrophile-lipophile balance (HLB) values of Cremophor EL and Span 80 on the phase behavior of the O/W microemulsions and the percutaneous absorption and penetration of indomethacin microemulsions. The existence of microemulsion regions is investigated in quaternary systems composed of soybean oil/Cremophor EL and Span 80 (mixed surfactants)/diethylene glycol monoethyl ether (cosurfactant)/water by constructing pseudo-ternary phase diagrams at various Cremophor EL/Span 80 ratios. In addition, five microemulsion formulations with various mixed surfactants HLB values were evaluated by in vitro penetration experiments using mouse skin and Franz diffusion cells. The flux and amount of indomethacin penetration from 5 microemulsion formulations were significantly different from the control, and the enhance ratios ranged from 2.38 to 4.68 and 2.11 to 4.23, respectively. The HLB value of mixed surfactants in the formulations was a principal factor in determining the percutaneous penetration of the drug. The flux and amount of drug penetration increased gradually with increasing content of the lipophilic surfactant Span 80 and skin retention was highest for mixed surfactants with a HLB value of 7.6. Therefore, it is suggested that the presence of mixed surfactants was beneficial in the formation of O/W microemulsions and enhanced percutaneous penetration of indomethacin.     

Effect of surface active agents on drug release from polylactic acid-hydrocortisone microcapsules

Polylactic acid microcapsules containing randomly distributed hydrocortisone particles were prepared. The rate of release of hydrocortisone from the microcapsules in pH 7.4 phosphate buffer was found to be largely increased by the presence of polysorbate 80, cetylpyridinium chloride, or aerosol OT in the dissolution medium. The surfactant effect was attributed to the ability of the surface active agent to improve solvent penetration into the microcapsules by lowering the surface tension at the solid-liquid interface. The effect of the cationic surfactant, cetylpyridinium chloride on the rate of drug release is similar in magnitude to that of the nonionic surfactant, polysorbate 80. In these systems, the rate of drug release from the microcapsules was found to be linearly related to the surface tension of the dissolution medium in the range of 40-60 dyn/cm (x 10(-3) N/m). In the same surface tension range, the effect of aerosol OT on rate increase was found to be much less than those of the cationic and nonionic surfactants. This suggests that the anionic surfactant is not well adsorbed at the interface due to the negative charge characteristics of the surface of the polylactic acid microcapsules. However, at nearly the critical micelle concentration of aerosol OT, where the corresponding surface tension is much lower than those of the cationic and nonionic surfactants, the microcapsules exhibited the highest rate of drug release.     

Match of Solubility Parameters Between Oil and Surfactants as a Rational Approach for the Formulation of Microemulsion with a High Dispersed Volume of Copaiba Oil and Low Surfactant Content

Purpose

Aim was to formulate oil-in-water (O/W) microemulsion with a high volume ratio of complex natural oil, i.e. copaiba oil and low surfactant content. The strategy of formulation was based on (i) the selection of surfactants based on predictive calculations of chemical compatibility between their hydrophobic moiety and oil components and (ii) matching the HLB of the surfactants with the required HLB of the oil.

Method

Solubility parameters of the hydrophobic moiety of the surfactants and of the main components found in the oil were calculated and compared. In turn, required HLB of oils were calculated. Selection of surfactants was achieved matching their solubility parameters with those of oil components. Blends of surfactants were prepared with HLB matching the required HLB of the oils. Oil:water mixtures (15:85 and 25:75) were the titrated with surfactant blends until a microemulsion was formed.

Results

Two surfactant blends were identified from the predictive calculation approach. Microemulsions containing up to 19.6% and 13.7% of selected surfactant blends were obtained.

Conclusion

O/W microemulsions with a high volume fraction of complex natural oil and a reasonable surfactant concentration were formulated. These microemulsions can be proposed as delivery systems for the oral administration of poorly soluble drugs.

     

Characterization of albumin-alginic acid complex coacervation

Complex coacervation of albumin and alginic acid has been investigated to characterize this process, and to prepare a microencapsulation system suitable for the encapsulation of live cells, protein and polypeptide drugs. The optimum conditions of pH, ionic strength and total polyion concentration were in accordance with predictions based on the method of Burgess & Carless (1984). Albumin/alginic acid complex coacervation appears to fit the Vies-Aranyi model for complex coacervation. Coacervation was limited compared with other polypeptide/polysaccharide systems such as gelatin and acacia, with albumin/alginic acid complex precipitates rather than complex coacervates forming under certain conditions. In particular coacervation was limited to concentrations below 0.5% w/v. At concentrations between 0.35 and 0.5% w/v both complex coacervation and precipitation occurred, and at concentrations above 0.5% w/v only precipitation was detected. The albumin/alginic acid complex coacervate is very viscous and this together with the limited conditions governing the occurrence of coacervation makes this system unsuitable for the preparation of microcapsules.     

Sucrose esters/cosurfactant microemulsion systems for transdermal delivery: Assessment of bicontinuous structures

This research studies microemulsion systems containing minimal amounts of surfactant for topical use. Sucrose esters are not able to form microemulsions without a cosurfactant. Microemulsion areas were investigated for numerous systems including sucrose esters/cetearyl octanoate/alcohols/water at different surfactant/cosurfactant mass ratios, called K_m, and different HLB values. The pseudoternary isotherm diagrams were constructed by titration at 25°C. The long and unsaturated oleic chain of the surfactant improves the extent of the microemulsion zone and when K_m increases the domain becomes larger. A combination of laurates at HLB = 7 increases the water and oil solubilizing capacity. Cosurfactants affect the shape and the extent of microemulsion regions. Shorter alcohols which are expected to disorder the interfacial film gave extended microemulsion zones by destabilizing the liquid crystalline phases. Moreover, in short alcohol based diagrams, the microemulsion areas are single volume in which the percolation transition law can be applied. The electroconductive behaviour allows us to determine the percolation threshold and to identify quantitatively bicontinuous structures. These structures, owing to their very low interfacial tension, associated to their wetting properties, should be very interesting as new drug carrier systems for transdermal delivery.     

PLGA microcapsules with novel dimpled surfaces for pulmonary delivery of DNA

We describe the fabrication of DNA-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules with novel surface morphologies that will be of use in pulmonary delivery. Our approach was to examine surface morphology and DNA encapsulation efficiency as a function of primary emulsion stability; using two surfactant series based on hydrophile-lipophile balance and hydrophobe molecular weight. Hydrophilic non-ionic surfactants yielded the most stable water-in-dichloromethane emulsions (HLB values >8). These surfactants normally favor convex (o/w) interfacial curvatures and therefore this atypical behavior suggested a relatively high surfactant solvation in the dichloromethane 'oil' phase. This was consistent with the large fall in the glass transition temperature for microspheres prepared with Tween 20, which therefore efficiently penetrated the PLGA matrix and acted as a plasiticizer. Blends of Pluronic triblock copolymers performed poorly as water-in-dichloromethane emulsifiers, and were therefore used to generate hollow microspheres ('microcapsules') with low densities (0.24 g/cm(3)). Although the Pluronic-stabilized emulsions resulted in lower DNA loading (15-28%), microspheres (approximately 8 microm) with novel dimpled surfaces were fabricated. The depth and definition of the dimples was greatest for triblock copolymers with high MW hydrophobe blocks. By cascade impaction, the geometric mean weight diameter of the microcapsules was 3.43 microm, suggesting that they will be of interest as biodegradable pulmonary delivery vehicles.     

Rheology and stability of water-in-oil-in-water multiple emulsions containing Span 83 and Tween 80

Multiple emulsions are often stabilized using a combination of hydrophilic and hydrophobic surfactants. The ratio of these surfactants is important in achieving stable multiple emulsions. The objective of this study was to evaluate the long-term stability of water-in-oil-in-water (W/O/W) multiple emulsions with respect to the concentrations of Span 83 and Tween 80. In addition, the effect of surfactant and electrolyte concentration on emulsion bulk rheological properties was investigated. Light microscopy, creaming volume, and rheological properties were used to assess emulsion stability. It was observed that the optimal surfactant concentrations for W/O/W emulsion long-term stability were 20% wt/vol Span 83 in the oil phase and 0.1% wt/vol Tween 80 in the continuous phase. Higher concentrations of Tween 80 had a destructive effect on W/O/W emulsion stability, which correlated with the observation that interfacial film strength at the oil/water interface decreased as the Tween 80 concentration increased. High Span 83 concentrations increased the storage modulus G′ (solidlike) values and hence enhanced multiple emulsion stability. However, when 30% wt/vol Span 83 was incorporated, the viscosity of the primary W/O emulsion increased considerably and the emulsion droplets lost their shape. Salt added to the inner aqueous phase exerted an osmotic pressure that caused diffusion of water into the inner aqueous phase and increased W/O/W emulsion viscosity through an increase in the volume fraction of the primary W/O emulsion. This type of viscosity increase imposed a destabilizing effect because of the likelihood of rupture of the inner and multiple droplets.     

The effect of surfactants on the microencapsulation and release of phenobarbitone from gelatin-acacia complex coacervate microcapsules

The effects of sodium lauryl sulphate (SLS), cetrimide and polysorbate 20 surfactants at concentrations below, at and above their critical micelle concentration (CMC) on the microencapsulation and release of phenobarbitone have been described. Bimodal particle size distributions were produced both in the absence and presence of each of the three surfactants. The presence of surfactant had little or no effect on the particle size distribution at any given stirring speed. A large variation was noted in the amount of phenobarbitone microencapsulated dependent upon the type of surfactant and its concentration. The amount of phenobarbitone encapsulated decreased with increasing concentration of polysorbate 20 and with SLS. Cetrimide (0.025 per cent w/v) enhanced encapsulation with 2 per cent w/w colloids but higher concentrations at the CMC and above decreased encapsulation. The results are explained in terms of decreased interfacial tension by the surfactant and by steric and electrostatic effects caused by surfactant adsorption onto the coacervate droplets and phenobarbitone particles.     

Influence of pH adjustment on microcapsules obtained from complex coacervation of gelatin and acacia

Abstract

The coacervation behaviour of commercial grade gelatin and acacia mixtures was studied with five different acids to adjust the coacervation pH, i.e. HCI, HNO₃, H₂SO₄, acetic acid, and citric acid. The electrical equivalence pH value (EEP) of the polymer mixture was determined by means of a streaming current detector (SCD). With all acids-except H₂SO₄-maximum coacervate yield was observed at the EEP. Using H₂SO₄ the EEP was found at a lower pH value than compared with the point of maximum coacervate yield. The quantity of coacervate at the EEP was significantly reduced in the presence of H₂SO₄ whereas with all other acids, almost no differences were found. The dependence of the coacervate volume on the added amount of acid did not change in parallel to the dry coacervate yield and there was no coincidence of the maximum coacervate volume and the EEP. The barrier properties of the capsule shells of corresponding microcapsules using indomethacin as a model drug were examined by dissolution studies. Indomethacin microcapsules showed the slowest release rate when the coacervation pH was adjusted to the EEP and not to the pH of maximum coacervate yield. As expected from the coacervation behaviour, dissolution profiles of the microcapsules were quite similar even when different acids were used for pH adjustment.     

Microencapsulation of O/W emulsions by formation of a protein-surfactant insoluble complex

Abstract

A method for obtaining microcapsules of oil droplets by the formation of an insoluble complex of protein-surfactant is described. The gelatin type A studied, which is positively charged at the pH range studied, may form insoluble and soluble complexes with sodium dodecyl sulphate (SDS), an anionic surfactant. The binding isotherms were studied and the specific molar ratios of SDS to gelatin, in which the insoluble complex is formed, was determined. These specific ratios also led to the formation of microcapsules, in which the wall encapsulating the oil droplets, is composed of the insoluble gelatin SDS complex.     

Studies on the development for sustained release preparation (II): Preparation and evaluation of eudragit microcapsules of sodium naproxen

The microencapsulation of sodium naproxen with Eudragit RS was studied by coacervation/phase separation process using Span 80 in mineral oil/acetone system. Various factors which affect the microencapsulation, e.g., stiming speed, and surfactant concentration, Eudragit RS concentration and loading drug amounts were examined. For the evaluation of the prepared microcapsules, release rate, particle size distribution and surface appearance as well asin vivo test were carried out. The addition of n-hexane and freezing of microcapsules accelerated the hardening of microcapsules. The optimum concentration of Span 80 to prepare the smallest microcapsules was the same value with the CMC of Span 80 in solvent system. When 1.5% (w/w) Span 80 was used, the smallest microcapsules were formed (30.02±5.05 μm in diameter) belonging to the powder category showing smooth, round and uniform surface. The release of sodium naproxen was retarded by microencapsulation with Eudragit RS. The Eudragit RS microcapsules showed significantly increased AUC and MRT and decreased Cl/F in rabbits.     

The effect of surfactants on the microencapsulation and release of phenobarbitone from gelatin-acacia complex coacervate microcapsules

Abstract

The effects of sodium lauryl sulphate (SLS), cetrimide and polysorbate 20 surfactants at concentrations below, at and above their critical micelle concentration (CMC) on the microencapsulation and release of phenobarbitone have been described. Bimodal particle size distributions were produced both in the absence and presence of each of the three surfactants. The presence of surfactant had little or no effect on the particle size distribution at any given stirring speed. A large variation was noted in the amount of phenobarbitone microencapsulated dependent upon the type of surfactant and its concentration. The amount of phenobarbitone encapsulated decreased with increasing concentration of polysorbate 20 and with SLS. Cetrimide (0025 per cent w/v) enhanced encapsulation with 2 per cent w/w colloids but higher concentrations at the CMC and above decreased encapsulation. The results are explained in terms of decreased interfacial tension by the surfactant and by steric and electrostatic effects caused by surfactant adsorption onto the coacervate droplets and phenobarbitone particles.     

Characteristics of medicated and unmedicated microglobules recovered from complex coacervates of gelatin-acacia.

Medicated and unmedicated microglobules prepared from complex coacervates of Type A gelatin and acacia were recovered as water-insoluble powders consisting of discrete units, which were spontaneously revertible to highly disperse systems when suspended in water or physiological electrolyte solutions. Spherical microglobules containing up to 15% (w/w) sulfamerazine had a nominal diameter of 30 micron in aqueous suspension. Larger but irregularly shaped products containing up to 45% (w/w) sulfamerazine were also recovered. The relationships of the weight of sulfamerazine added per coacervate batch to weight yield and percent (w/w) included sulfamerazine of the microglobules were both linear.     

Gelatin coacervate microcapsules containing sulphamerazine: their preparation and the in vitro release of the drug

An improved method is described for the preparation of gelatin coacervate microcapsules containing sulphamerazine as a fine deflocculated powder. The factors which control both the coacervation step and the recovery of the microcapsules are discussed. The in vitro release of sulphamerazine from microcapsules of different wall thickness which had been hardened by formaldehyde under different conditions has been studied. The method of preparation gave a high percentage of encapsulated material in comparison with other recovery techniques.     

Development and characterization of different low methoxy pectin microcapsules by an emulsion-interface reaction technique

In the controlled release area, biodegradable microcapsules are one of the most useful devices to deliver materials in an effective, prolonged and safe manner. A new charged film microcapsular carrier system, using three different pectins, is described. The study utilized pectin microcapsules prepared by two encapsulation mechanisms of interfacial reaction explored through interaction of charged droplet-oil-anionic surfactant-calcium or oil-cationic surfactant with negatively charged pectin. A method for drug encapsulation was developed based on the type of pectin, surfactants and emulsification technique. Both types of surfactant, anionic sodium dodecyl sulphate (SDS) and cationic benzalkonium chloride (BzACl) promoted polymer film formation on the oil droplet surfaces, probably through cross-linking and electrostatic interaction, respectively. Microcapsules consisting of pectin as shell and hydrophobic oil as core were characterized. The resulting microcapsules were relatively small particles (d< 3 microm), had high total particle number, specific surface area and drug encapsulation efficiency. They also demonstrated good stability with minimum particle aggregation. Correlation between physicochemical and drug release kinetic parameters were investigated with regard to the effect of pectin macromolecular structure and nature of surfactant used as a counterion in the manufacturing of microcapsules. The release rate of the encapsulated material (prednisolone) in three microcapsules can be controlled by manipulating the conformational flexibility of pectins in the presence of different counterions. As a result, biodegradable pectin microcapsules offer a novel approach for developing sustained release drug delivery systems that have potential for colonic drug delivery.     

Formulation of electrically conducting microemulsion-based organogels

Gelatin-containing, electrically conducting, rigid water-in-oil (w/o) microemulsion-based organogels (MBG), both with and without the presence of a model drug, have been prepared using pharmaceutically acceptable oils and surfactants. As a precursor to MBG formation, preliminary formulation work was carried out investigating the factors affecting the preparation of w/o microemulsions containing large amounts of dispersed aqueous phase. From these studies isopropyl myristate (IPM) was favoured as oil due to its ability to support w/o microemulsion formation over a wide range of compositions. The single most effective surfactant for stabilising the w/o microemulsions was found to be Aerosol-OT (AOT), although synergistic effects on the extent of w/o microemulsion formation were observed upon its combination with a variety of non-ionic surfactants. Upon addition of gelatin to the w/o microemulsion, MBG could be formed when using AOT as stabiliser with most of the oils investigated (with the exception of the medium and large triglyceride oils, Miglyol 812 and soybean oil, respectively) and with a number of AOT/non-ionic surfactant/IPM combinations (both in the presence and absence of model drugs such as sodium salicylate). MBG could not however be formed with non-ionic surfactants alone, or when used in combination with another non-ionic surfactant (regardless of the oil used). This latter observation was found to be not only a result of the inadequate level of water available for hydration of the surfactant head group and any gelatin present but also a consequence of the inability of these systems to form, upon heating, the percolated microstructures necessary to facilitate the supramolecular assembly of gelatin at the macroscopic level, a pre-requisite for MBG formation.