Microencapsulation with carrageenan-locust bean gum mixture in a multiphase emulsification technique for sustained drug release

Abstract

A multiphase emulsification technique was modified in this process of microencapsulating gentamicin sulphate, thus avoiding the necessity for a surfactant in preparing the secondary emulsion for a W/O/W emulsion. Various proportions of iota-carrageenan (i-C) and locust bean gum (LBG) were investigated for the W/O/W emulsion after forming the primary W/O emulsion with sorbitan trioleate, Span 85. Upon removal of the oil phase (chloroform) from the W/O/W emulsion by heating (60-65°C), microcapsules or ‘W/W particles containing drug dissolved in sodium hyaluronate were spontaneously formed. These were dispersed in a solution of a mixture of 5-10 per cent w/v polyvinyl alcohol, PVA (average MW 50000-106000; 98 per cent hydrolysed) and 3 per cent v/v polyethylene glycol 200 (PEG 200), and dried to form the hydrogel film casts. Our in vitro experiments in isotonic phosphate buffer solution (pH 7-4) at 37°C., showed that the release of gentamicin sulphate was dependent on concentration of LBG, and concentration or molecular weight of PVA. With the exception of PVA hydrogel matrix preparations containing 20 per cent w/v LBG, all other formulations showed a significant initial ‘burst' release of drug within 6h. The drug-containing microcapsules in the PVA hydrogel film with 20 per cent w/v LBG, exhibited an almost zero-order release of drug up to 140h. It is postulated that an effective barrier or high-density membrane enveloping the microcapsules was formed between i-C and LBG because of their unique molecular configurations. This phenomenon, together with the possible adsorption of i-C molecules at the transient oil and outer aqueous phase interface, presumably eliminated the need for a permanent oil phase and/or an O/W surfactant normally required for preparing W/O/W emulsions.     

Hypoglycemic effect of surfactant-coated insulin solubilized in a novel solid-in-oil-in-water (S/O/W) emulsion

A novel solid-in-oil-in-water (S/O/W) emulsion for oral administration of insulin has been developed using surfactant-coated insulin. The S/O/W emulsion prepared by a shirasu porous glass (SPG) membrane provided a sharp size distribution and was stable. Leakage of insulin from the S/O/W emulsions was not observed for several days. The S/O/W emulsion showed the hypoglycemic activity for a long period after oral administration to rats.     

Microencapsulation of blackberry pulp with arrowroot starch and gum arabic mixture by spray drying

Abstract

This research work aimed to obtain blackberry pulp powder by spray drying and, by an experimental design, evaluated the effect of inlet air temperature (100–150?°C) and blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:0.5–1:2 on the physicochemical properties of the powders. Arrowroot starch and gum arabic present glass transition temperature (Tg) values above 100?°C; hence it was possible to employ them as carriers in blackberry pulp spray drying in order to increase Tg of the system. Powder yield and solubility increased with increasing blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:0.5–1:2, whereas hygroscopicity decreased. Yield, solubility and hygroscopicity of the powders increased and water activity decreased, with increasing inlet air temperature. The powders presented low moisture content and water activity. Temperature of 143?°C and blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:1.78 were the optimal conditions to obtain high yield and blackberry powders that are soluble in water and less hygroscopic.     

Microencapsulation of cocoa liquor nanoemulsion with whey protein using spray drying to protection of volatile compounds and antioxidant capacity

Abstract

The aim of this study was microencapsulated a nanoemulsion of cocoa liquor with whey protein by spray drying, and evaluate the effect of different inlet drying temperatures on the properties of microcapsules. The nanoemulsion showed a particle size of 202.13?nm, PdI of 0.424, and ζ-potential of ?25.20?mV. The inlet drying temperature showed differences in physicochemical properties of microcapsules. Microcapsules presented good thermal stability and protection against the melting of cocoa liquor. Microcapsules obtained showed excellent yields of polyphenolic compounds (78–93%), and high retention of volatile compounds, especially of pyrazines. Greater microencapsulation yield of bioactive compounds and retention of volatile compounds was obtained at higher drying temperature (180?°C). Excellent stability of polyphenols content, antioxidant capacity, and volatile compounds of cocoa liquor were observed during storage of the microcapsules at different temperature conditions, indicating the feasibility of this powder for its incorporation into functional foods.     

Water-soluble betamethasone-loaded poly(lactide-co-glycolide) hollow microparticles as a sustained release dosage form

In this study, betamethasone disodium phosphate-loaded microparticles were fabricated for sustained release using poly(lactide-co-glycolide) (PLGA) by spray drying and emulsion solvent evaporation/extraction techniques. Encapsulation efficiencies ranged from 59–80% using a water-in-oil-in-oil (W/O/O) double emulsion technique and more than 90% for a spray-drying method were obtained. This was a significant improvement compared to fabrication by a water-in-oil-in-water (W/O/W) double emulsion process, which had an encapsulation efficiency of less than 15%. Multiple-phase and biphasic release profiles were observed for microparticles of PLGA 50/50 and PLGA of higher lactide contents, respectively. The PLGA 50/50 hollow microparticles fabricated using the W/O/O double emulsion technique provided a sustained release of betamethasone disodium phosphate over 3 weeks.     

Water-soluble betamethasone-loaded poly(lactide-co-glycolide) hollow microparticles as a sustained release dosage form

In this study, betamethasone disodium phosphate-loaded microparticles were fabricated for sustained release using poly(lactide-co-glycolide) (PLGA) by spray drying and emulsion solvent evaporation/extraction techniques. Encapsulation efficiencies ranged from 59-80% using a water-in-oil-in-oil (W/O/O) double emulsion technique and more than 90% for a spray-drying method were obtained. This was a significant improvement compared to fabrication by a water-in-oil-in-water (W/O/W) double emulsion process, which had an encapsulation efficiency of less than 15%. Multiple-phase and biphasic release profiles were observed for microparticles of PLGA 50/50 and PLGA of higher lactide contents, respectively. The PLGA 50/50 hollow microparticles fabricated using the W/O/O double emulsion technique provided a sustained release of betamethasone disodium phosphate over 3 weeks.     

Preparation of soft microcapsules containing multiple core materials with interfacial dehydration reaction using the (W/O)/W emulsion

The soft microcapsules containing eucalyptus oil, ubiquinone and the fine water droplets could be prepared with interfacial dehydration reaction between hydroxy methyl cellulose and tannic acid using the water-in-oil-in-water type multiple (W/O)/W emulsion. The diameters of the microcapsules and the content and the microencapsulation efficiency of the core materials were significantly affected by the revolution velocity (Nr₁) to form the (W/O) emulsion and the revolution velocity (Nr₂) to form the (W/O)/W emulsion and the lecithin concentration. The mean diameters of the inner water droplets and those of the microcapsules were proportional to Nr₁^?1.25 and Nr₁^?0.11 for the revolution velocity (Nr₁), respectively. With increasing the revolution velocity (Nr₁), the content and the microencapsulation efficiency of the inner water droplets increased, while those of the oil phase decreased. The mean diameters of the microcapsules were proportional to Nr₂^?1.1. The content and the microencapsulation efficiency of the inner water droplets and those of the oil phase decreased with the revolution velocity (Nr₁) and increased with the lecithin concentration.     

Microencapsulation of acetaminophen into poly(L-lactide) by three different emulsion solvent-evaporation methods

Poly(L-lactide) (PLLA) microcapsules containing acetaminophen (APAP) were prepared by three emulsion solvent-evaporation methods including an O/W-emulsion method, an O/W-emulsion co-solvent method and a W/O/W-multiple-emulsion method. The average size and morphology of the microcapsules varied substantially among these three preparation methods. Various alcohol and alkane co-solvents were found to exert significant impact on the O/W-emulsion co-solvent method and a more lipophilic co-solvent such as heptane appeared to enhance drug encapsulation with an efficiency nearly double of the O/W-emulsion method. When a small amount of water was added as the internal aqueous phase in the W/O/W-multiple-emulsion method, the encapsulation efficiency was found nearly triple of that for the O/W-emulsion method. While having a higher encapsulation efficiency, the microcapsules prepared by the W/O/W-multiple-emulsion method had as good controlled release behaviour as those prepared by the O/W-emulsion method. The release kinetics of microcapsules prepared by the O/W-emulsion method and the O/W-emulsion co-solvent (alcohol) method fitted the Higuchi model well in corroboration with the uniform distribution of APAP in PLLA matrix, i.e. the monolithic type microcapsules. However, the release kinetics of microcapsules prepared by the O/W-emulsion co-solvent (alkane) method and the W/O/W-multiple-emulsion method fitted the first-order model better, indicating the reservoir type microcapsules.     

Water-in-oil-in-water double emulsions loaded with chlorogenic acid: release mechanisms and oxidative stability

Abstract

Chlorogenic acid (CA) is a natural compound used as an antioxidant in the preparation of food, drugs, and cosmetics. Due to their low stability and bioavailability, many researchers have studied the encapsulation of CA in various delivery colloidal systems. The aim of this study was to evaluate the stability of water-in-oil-in-water (W/O/W) double emulsions loaded with CA and its antioxidant capacity. For this purpose, CA-W/O/W double emulsions were prepared using Span 80 and lecithin as lipophilic emulsifiers, and Tween 20 as a hydrophilic emulsifier. The influence of nature of lipophilic emulsifiers, the presence of chitosan (CH) in the internal and external aqueous phases, pH, temperature and the storage time of W/O/W double emulsions were also investigated. Depending on the preparation conditions, the W/O/W double emulsions showed the droplet size in the range 9.13?±?0.55?μm–38.21?±?1.87?μm, the creaming index 34%–78% and the efficiency encapsulation 79.45?±?1.5%–88.13?±?1.9%. Zeta potential values were negative for the W/O/W double emulsion without CH (?36.8?±?2.02mV; ?27.3?±?1.75mV) and positive for the W/O/W double emulsions with CH in the external aqueous phase (+6.5?±?0.42mV; 28.6?±?0.92mV). The study of the release of CA from W/O/W double emulsions has highlighted two mechanisms: one based on the coalescence between the water inner droplets or between the oil globules as well as a diffusion releasing mechanism. The oxidative stability parameters of the W/O/W double emulsions, such as the peroxide value (POV) and the conjugated diene content (CD) were measured.     

Microencapsulation of acetaminophen into poly(L-lactide) by three different emulsion solvent-evaporation methods

Poly(L-lactide) (PLLA) microcapsules containing acetaminophen (APAP) were prepared by three emulsion solvent-evaporation methods including an O/W-emulsion method, an O/W-emulsion co-solvent method and a W/O/W-multiple-emulsion method. The average size and morphology of the microcapsules varied substantially among these three preparation methods. Various alcohol and alkane co-solvents were found to exert significant impact on the O/W-emulsion co-solvent method and a more lipophilic co-solvent such as heptane appeared to enhance drug encapsulation with an efficiency nearly double of the O/W-emulsion method. When a small amount of water was added as the internal aqueous phase in the W/O/W-multiple-emulsion method, the encapsulation efficiency was found nearly triple of that for the O/W-emulsion method. While having a higher encapsulation efficiency, the microcapsules prepared by the W/O/W-multiple-emulsion method had as good controlled release behaviour as those prepared by the O/W-emulsion method. The release kinetics of microcapsules prepared by the O/W-emulsion method and the O/W-emulsion co-solvent (alcohol) method fitted the Higuchi model well in corroboration with the uniform distribution of APAP in PLLA matrix, i.e. the monolithic type microcapsules. However, the release kinetics of microcapsules prepared by the O/W-emulsion co-solvent (alkane) method and the W/O/W-multiple-emulsion method fitted the first-order model better, indicating the reservoir type microcapsules.     

Oral-Antigen Delivery via a Water-in-Oil Emulsion System Modulates the Balance of the Th1/Th2 Type Response in Oral Tolerance

Purpose. To evaluate the ability of a water-in-oil (W/O) emulsion containing ovalbumin (OVA), a model antigen, to induce oral tolerance and to elucidate the mechanism for the induction of oral tolerance by the emulsion system. Methods. A W/O emulsion containing OVA was prepared and evaluated its ability to induce oral tolerance in mice. Also, the Th1/Th2 balance in the mice tolerized was investigated in terms of the ratios of anti-OVA IgG2a titer to anti-OVA IgG1 titer (IgG2a/IgG1 ratios) and cytokine profiles. Results. Anti-OVA total IgG antibody titer of mice administered OVA in saline was approximately 3.5-fold higher than that of the mice administered OVA in W/O emulsion at a dose of 0.1 mg/mouse/day. Similar total IgG responses were observed between the above two at a dose of 1 mg/mouse/day. The IgG2a/IgG1 ratios decreased as the dose of OVA in W/O emulsion, but not in saline, increased at doses of 0, 0.1, and 1 mg/mouse/day. Interferon- secretion of PLN cells from the mice administered OVA in W/O emulsion decreased, whereas their interleukin-4 secretion remained high. Although interferon- secretion for the mice administered OVA in saline decreased, interleukin-4 secretion did not change. Conclusions. The present study suggests that oral delivery of OVA via the W/O emulsion system may more efficiently enhance the induction of Th2-dominated imbalance than that of OVA in saline.     

Influence of the primary emulsification procedure on the characteristics of small protein-loaded PLGA microparticles for antigen delivery

Microparticles prepared from poly(lactic-co-glycolic acid) (PLGA) using a W1/O/W2 double emulsion solvent evaporation method are suitable vehicles for the delivery of proteins to antigen presenting cells, e.g. dendritic cells. In this study, the influence of different techniques for the preparation of the primary W1/O emulsion was investigated with respect to the protein localization within the microparticles, morphological characteristics of these particles, protein burst release and the native state of the released protein. Bovine serum albumin bearing fluorescein isothiocyanate (FITC-BSA) was used as model protein. A static micromixer was applied for the preparation of the W1/O/W2 double emulsion. Employing a rotor-stator homogenizer (Ultra-Turrax) for primary emulsification, microcapsules with a high burst release were produced, because nearly all FITC-BSA was attached to the outside of the particle wall. Using a high pressure homogenizer or an ultrasonic procedure resulted in the formation of microspheres with homogeneous protein distribution and a reduced burst release.     

Preparation of stable W/O/W type multiple emulsion containing water-soluble drugs and in vitro evaluation of its drug-releasing properties]

The stable water-in-oil-in-water (W/O/W) multiple emulsion was prepared by a two-step procedure for emulsification using glyceryl tricaprylate (Panasate-800) as the oil phase. The water-soluble drugs such as cefadroxil, cephradine, 4-aminoantipyrine, and antipyrine were selected and entrapped separately in the inner aqueous phase of W/O/W multiple emulsion. In consideration of parenteral administration, pH 7.4 phosphate buffered saline was used in both inner and outer aqueous phases. Moreover, these multiple emulsions could be significantly stable for a month at room temperature by the addition of hydrophilic polymer like gelatin and of amino acid like lysine to the inner aqueous phase.     

W/O/W型薄荷油复乳的制备及其性质初步研究

目的制备薄荷油W/O/W型复乳,并对其性质进行初步研究。方法采用二步法制备薄荷油W/O/W型复乳,对其物理性质如:外观、显微形态、乳剂类型、粘度、表面张力、相变温度、物理稳定性等方面进行初步研究。结果薄荷油W/O/W型复乳外观呈白色、外相能被曙红指示液染色、室温下的粘度为15.2 mPa.S,表面张力为30×10-3N.m-1,相变温度为84℃。结论二步法制备薄荷油W/O/W型复乳物理稳定性较好。     

Slow release of chloroquine phosphate from multiple taste-masked W/O/W multiple emulsions

Abstract

The efficacy and safety of chloroquine as an antimalarial has contributed to the survival of millions in the past 50 years. Chloroquine is widely available, cheap, well tolerated and orally well absorbed. Therefore, it remains an important antimalarial drug. However, on oral administration, particularly to children, the unpleasant taste is a problem. This could be avoided by ‘taste-masked and controlled release’ formulations such as multiple emulsions. Although Plasmod-ium falciparum has developed resistance to many antimalarial drugs, including chloroquine, resistance may be attributed, among other factors, to subclinical dosage of chloroquine from administered pharmaceutical forms. This could also be relevant in the treatment of rheumatoid arthritis. Multiple W/O/W emulsions of chloroquine phosphate were prepared. Assessment of emulsion stability showed no significant change in the system. Prolonged storage (four months) of the emulsion resulted in negligible loss of chloroquine phosphate. The results suggest, therefore, that chloroquine phosphate releases due to diffusion of the drug from the internal globules and not as a consequence of instability of the W/O/W emulsion. These characteristics are in accordance with the requirements for controlled release Pharmaceuticals. Stability of multiple emulsions could have resulted from interfacial polymerization or complexion between molecules. Release assessments showed faster rates for W/O/W emulsions which had smaller internal aqueous globules and, therefore, an increased interfacial area. Furthermore, transport of high-diffusion coefficient micelles could have given a greater solute flux in these systems.     

Effect of poplar-type propolis on oxidative stability and rheological properties of O/W emulsions

Propolis is known to possess antioxidant activity. However, there is no information on this activity in emulsions O/W. The protective effect of propolis on the oxidation and rheological properties of emulsions O/W containing wheat germ and almond oils was evaluated. Emulsions O/W were prepared with different concentration of propolis extract, almond oil and wheat germ oil. All emulsions physically stable without phase separation were stored at 37?°C for 9?weeks. Chemical composition of propolis was established by Gas chromatography coupled to mass spectrometry. Rheological characterization of different emulsions was performed evaluating consistency index and flow behavior index. The oxidation was monitored by measuring the lipid hydroperoxides and thiobarbituric acid-reactive substances (TBARS) methods. Flavonoids, phenolic acid esters, and aromatic acids were the main groups of compounds found in propolis. The results showed that popolis was good antioxidant in the concentration of 0.02 and 0.04% when lipid phase was constituted by almond oil. The rheological behavior is typical of a non-Newtonian fluid, being almond oil more adequate for having a higher stable O/W emulsion.     

Process and formulation variables in the preparation of wax microparticles by a melt dispersion technique. II. W/O/W multiple emulsion technique for water-soluble drugs

Abstract

Pseudoephedrine HCl-carnauba wax microparticles were prepared by a multiple emulsion-melt dispersion technique. A heated aqueous drug solution was emulsified into the wax melt (W/O emulsion), followed by emulsification of this primary emulsion into a heated external aqueous phase (W/O/W emulsion). The drug-containing microparticles were formed after cooling and congealing of the wax phase. The encapsulation efficiencies were above 80 per cent and actual drug loadings close to 50 per cent were achieved. The surface of the microparticles had submicron pores and drug crystals were visible on cross-sections. The drug loading depended on the rate of cooling and the volume of the internal aqueous phase but was insensitive to the volume of the continuous phase. The drug release was much faster when compared to the release from polymeric microspheres.     

W/O/W multiple emulsions of insulin containing a protease inhibitor and an absorption enhancer: preparation,characterization and determination of stability towards proteases in vitro

W/O/W multiple emulsions composed of medium-chain triglycerides containing insulin with aprotinin, a protease inhibitor, and/or sodium taurocholate, an absorption enhancer, were prepared by a two-step emulsification method at 15°C. Whatever the nature of the substance introduced in the internal aqueous phase, all the emulsions obtained had very similar properties. The yield of insulin encapsulation, measured by HPLC analysis, was approximately 95%. These systems were stable during at least 3 months of storage at 4–6°C. The main release mechanism was a swelling-breakdown phenomenon after dilution of the emulsions under hypo-osmotic conditions. These emulsions were able to protect insulin against enzymatic degradation in vitro.     

Study of the Breakup Under Shear of a New Thermally Reversible Water-in-Oil-in-Water (W/O/W) Multiple Emulsion

Purpose. Thickening of the external aqueous phase of W/O/W multiple emulsions is essential to increase the release under shear. However, it leads to globules bursting during fabrication. To reduce this problem, we have tested a novel thermally reversible hydrogel, EMP hydrogel. This way, the corresponding multiple emulsion (EMPME) would gel only at skin temperature, which may increase the active ingredient delivery when topically applied. Methods. Samples were sheared at different shear rates and temperatures (20, 30, and 35°C) with a controlled rheometer. A granulometric analysis was then performed with a laser diffraction granulometer, to assess the break up as a function of the shear rate at the three temperatures. Conductometric measurements (CDM 230 conductometer) provided the corresponding release curves. Results. As we expected, EMPME exhibited a thermally reversible behavior. Compared to a reference emulsion thickened by carbopol, this new thermo–sensitive multiple emulsion displayed higher break up and fraction released at 35°C. Conclusion. The first thermally reversible multiple emulsion has been developed in the present work. This one presents interesting advantages: (1) an easy fabrication process with a higher entrapment yield and (2) a higher fraction released at 35°C compared with the reference emulsion.     

Preparation of microcapsules and control of their morphology

For the preparation of microcapsules using the W/O/W (water in oil in water) emulsion system, it is essential to control various factors such as the dispersed state of the organic phase in the W/O/W emulsion, the difference in the solute concentration between the inner and outer aqueous phases and the volume fraction of the dispersed phase. In this study, cross-linked microcapsules were prepared by the in-situ polymerization of styrene and divinylbenzene and biodegradable microcapsules were prepared by the solvent evaporation method. The effects of the preparation conditions on the capsule morphology and entrapment efficiency of water-soluble materials were investigated. The average diameter of the surface pores and internal hollows were controlled on a sub-micron order by changing the preparation conditions such as diluent concentration, volume fraction of the dispersed droplets in the W/O (water in oil) emulsion, surfactant concentration monomer ratio and salt concentration in the outer aqueous phase. Furthermore, the water-soluble materials were completely entrapped in the biodegradable microcapsule by changing the preparation conditions such as volume fraction of the dispersed droplets in the W/O emulsion, salt concentration in the inner and outer aqueous phases, polymer concentration and supersonic irradiation of the W/O droplets.