Potentials of Liquid Membrane System : An overview

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Azhar Yaqoob khan

Azhar Y Khan

Liquid membrane system is basically known as stabilized water-in-oil-in-water multiple emulsion (w/o/w) system, in which two miscible phases are separated by an organic phase.

Liquid membrane acts as a thin semi-permeable film through which solute must diffuse moving from one phase to another. These systems are exhibiting unlimited potential because of their vesicular structure with innermost phase closely similar to that of liposomal vesicles and their selective permeability characteristics.

Based on these facts, a liquid membrane system has been extensively studied with respect to their practical utility. This review summarizes formulation aspects and explores the various applications of liquid membrane systems in the last few decades.  

1.0 Introduction:

Among the recent drug delivery systems such as nanospheres, microspheres, microemulsions, emulsion particles,self-emulsifying drug delivery system, liposomes and mixed micelles, most of the research is based on the lipid based drug delivery system. These systems have been explored as potential colloidal carrier systems either for delivery or for targeting purposes.1,2 Emulsions are heterogeneous systems where two immiscible liquids are being placed together and made stable by an emulsifying agent. An emulsion can be defined as dispersion of droplets of one liquid in another one with which it is incompletely miscible.3 Typically emulsion contains oil and water phases where the less polar liquid represent oil phase and the more polar one represents the water phase. Depending on how the oil and water phases are being placed in dispersed system, there can be several types of emulsions.4 Simple emulsions can be either oil-in-water (o/w) or water-in-oil (w/o) depending on whether oil phase is dispersed in continuous aqueous phase, or water phase is dispersed in continuous oil phase respectively. Micro- and nanoemulsions are now being under investigation where the dispersed phase is in micrometer and nanometer range respectively. These can also be of two types i.e. oil-in-water (o/w) or water-in-oil (w/o).

Multiple emulsions are polydispersed systems where both water in oil and oil in water emulsion exists simultaneously in a single system. Lipophillic and hydrophilic surfactants are used for stabilizing these two emulsions respectively. Multiple emulsions can be w1/o/w2 or o1/w/o2 depending on the dispersed phases in dispersion media. These are called as emulsions of emulsions because one simple emulsion is placed inside another one. In multiple emulsion system solute has to transverse through the middle immiscible organic phase (liquid membrane) in order to come from inner miscible phase to outer miscible phase, therefore also called as liquid membrane system.5,6 Water-in-oil-in-water (w/o/w) system has advantages over oil-in-water-in-oil (o/w/o) as the former  having water as an external phase, therefore promising wider areas of application. Multiple emulsions possess several advantages over other delivery systems, which make them a challenging drug delivery system. Liquid membrane system possesses adequate biocompatibility, complete biodegradability and versatility in terms of different oils and emulsifiers being used. They can be used for the entrapment of both hydrophilic and hydrophobic drugs, protection of the entrapped compound, drug targeting specially to reticuloendothelial system (RES), taste masking and for slow or controlled delivery of drugs. Beside these advantages with multiple emulsions, there are certain associated disadvantages like being difficult to formulate, bulky and susceptible to various routes of physical and chemical degradation. Multiple emulsions have not been commercially exploited because of their inherent thermodynamic instability. A number of attempts have been made in last two decades for improving stability by several investigators. In broad terms stabilization techniques used for liquid membrane system could concentrate on any of the following heads; polymerization gelling, additives in different phases, surfactant concentration modulation, interfacial complexation, pro-multiple emulsion approach and steric stabilization. Many authors have reviewed the different stabilization methods and different drug release mechanisms.7-9

2.0 Formulation Approaches

In multiple emulsion especially in w/o/w formulation, engineering intention is to use two surfactants in the system, where first lipophillic surfactant stabilizes w/o primary emulsion while the second one being hydrophilic in nature stabilizes o/w emulsion ultimately resulting in a w/o/w emulsion. The most common method of formulation is two-step emulsification method (Double Emulsification Technique). This method is easy, reproducible and gives a high percentage yield. In this method, an ordinary w/o or o/w primary emulsion is first prepared which is then re-emulsified in  an excess amount of aqueous phase or oil phase to produce w/o/w or o/w/o type emulsion, respectively. Different equipments can be used for the emulsification purposes like homogenizer, ultrasonicator, stirrer, mixer etc. Currently, a modified two-step emulsification method is being used to provide high yield and stable multiple emulsion.10, 11 Other techniques for formulations are phase inversion, membrane emulsification and microchannel emulsification. Earlier, phase inversion technique was widely used for the formulation of emulsions but the technique provided multiple emulsion with wide and irregular globule size distribution which could lead to instability, therefore, it is not highly prevalent now a days.12 Membrane emulsification technique involves dispersion of one immiscible phase (dispersing phase) to outer phase (continuous phase) by pressure through the required membrane pore size. Being a new, convenient and useful technique, this has been used as emulsifying tool for preparation of multiple emulsions of cytarabine, doxorubicin and vancomycin.13, 14 Micro channel emulsification, a novel technique was also used successfully for preparing multiple emulsion with ethyl oleate and medium-chain triglyceride as oil phases. This technique involves forced extrusion of the dispersed phase through the elongated channels (Disk-like shape) of desired diameter. This distorted disk-like shape provides high interface free energy which is essential for transformation into spherical droplets, requiring low energy input in comparison to conventional emulsification techniques. Interfacial tension is being exploited as the driving force for droplet formation. The droplet size can be controlled by microchannel geometry easily. This technique can also be used as a second step in two-step emulsification method.15

There are various formulation variables, which affect the development of formulation of multiple emulsion. Oils and emulsifiers constitute the main components of any emulsion system. These are primary components and affect nature, yield, consistency, stability and use of emulsions. Type of emulsifier affect the preparation and stability of multiple emulsion system.16, 17  Mostly non-ionic surfactants are used for the preparation of emulsions for pharmaceutical use, because of the low toxicity, inertness  and high yield in comparison to ionic surfactants.5,10,18 Thermal stability of multiple emulsion can be increased with blend of biopolymer/polysaccharide complexes which primarily depend on surface properties of the complexes. Biopolymer /polysaccharide ratio strongly affects the potential of these surfactants.19 Recently, a matured gum arabic, (Acacia SUPER GUM™) has been explored for emulsifier potential for stabilization and increased encapsulation capacity in w/o/w multiple emulsion due to its wide pH range stability.20

Nature of oil is another factor which influences stability because it not only controls the viscosity of the multiple emulsions but also the permeability of the membrane, hence the diffusion of solute across oil membrane. Oils used in the preparation of pharmaceutical emulsions are of various types, including simple esters, fixed and volatile oils, hydrocarbons and terpenoid derivatives. The oil itself may be the medicament or it may function as a carrier for a drug, or even form part of a mixed emulsifier system as in the case of some fixed oils that contain sufficient free fatty acids. The most widely used oils in oral preparations are nonbiodegradable oils or various fixed oils of vegetable origin (e.g., arachis, cottonseed, and maize oils) and animal origin fish liver oil as nutritional supplements. Mineral oils give higher yield than vegetable oils.5,6,21 Oils of varying density and viscosity have been used for altering drug release characteristics.22 Generally primary phase volume (Fw/o) does not affect the yield but secondary phase volume (Fw/o/w) influences % yield of multiple emulsion.18,23 There are very few reports available on the use of very high phase volume ratio (70-90%).24.25 Change in temperature during formulation also influences yield and stability because it changes the characteristic of the hydrophilic emulsifier. As a thumb rule, generally primary emulsions are being formulated at higher temperature as compared to secondary emulsification.26,27 Similarly shearing also affects the stability, as higher shear stress causes frothing and air entrapment where as low shear leads to big size globules. In general secondary emulsification is performed at low shear rate in comparison to primary emulsification because it can lead to the breaking of multiple drops.5,10,18,28 Models have been devised for prediction of viscosity behavior of multiple emulsions. According to these models, the relative viscosity of multiple emulsions depend on four variables: volume fraction of internal droplets within a multiple emulsion droplet, volume fraction of total dispersed phase in the whole multiple emulsion, ratio of primary-emulsion matrix viscosity to multiple-emulsion matrix viscosity and ratio of internal droplet viscosity to primary-emulsion matrix viscosity. With the increase in any of these variables, the viscosity of the multiple emulsion generally increases.29  

Drug Release Kinetics

The journey  of drug from the internal to external phase across the liquid membrane is important, especially in pharmaceutical systems where this system is envisaged as possible controlled release drug delivery system. The release kinetics of the liquid membrane systems are affected by the various factors such as droplet size, pH, phase volume and viscosity etc. There are several possible mechanisms for drug release across the liquid membrane phase (oil membrane).5 Rather than a single mechanism, combination of various mechanisms are responsible for drug release and hence the exact release mechanism remains unclear. Plausible mechanisms for the drug release includes-

1) Diffusion mechanism:

This model suggests the diffusion of the unionized drug (Hydrophobic species) through the rate controlling oil membrane. This is most obvious transport mechanism where unionized hydrophobic drug diffuses through the oil layer (Semi permeable liquid membrane) in the stable multiple emulsion. Drug transport has been found to follow first order kinetics and obeyed Fick’s law of diffusion.30

(2) Micellar transport:

Inverse micelles play key role in this transport mechanism. Inverse micelles consisting of nonpolar part of surfactant lying outside and polar part inside encapsulate hydrophilic drug in core and permeate through the oil membrane because of the outer lipophillic nature.  Theses micelle can be of both surfactants facilitating formation of water swollen inverse micelle. Inverse micelle can encapsulate both ionized and unionized drugs.31 Recently, the release of tetradecane from a tetradecane/water/hexadecane multiple emulsion was investigated using the differential scanning calorimetry technique. Micellar diffusion rather than molecular diffusion was considered to be the preponderant mechanism for mass transfer.32

(3) Thinning of the oil membrane:

As the name of this mechanism suggests, transport of water through thin oil membrane region. In this area, it is easier for the water or drug to permeate because of small oily region. Thinning of the oil membrane takes place primarily due to osmotic pressure difference between two aqueous phases. This pressure difference also provides force for the transverse of molecule.33

(4) Rupture of oil phase:

Rupturing of the oil membrane is another possible mechanism of release from multiple emulsion. According to this mechanism rupturing of oil membrane can unite both aqueous phases and thus drug could be released easily.33

(5) Facilitated diffusion (Carrier-mediated transport):

This mechanism involves a special molecule (carrier) for the transfer of hydrophilic, ionic molecule from internal to external aqueous phase. This carrier molecule combines with the drug and makes it compatible to permeate through the oil membrane (lipophilic, nonionic). This type of mechanism behaves like ‘pumping system’ where the carrier molecule act as pump and transfer drugs from internal to external aqueous phase. These special compounds acting as carrier can be incorporated in internal aqueous phase or oil membrane.

(6) Photo-osmotic transport:

The mechanism of this transport process is not very clear. Transport of the drug through the oil membrane takes place with the help of the light.34,35

(7) Solubilization of internal phase in the oil membrane:

It is a conspicuous transport mechanism. In this solubilization of minute amounts of the internal phase in the membrane phase results in the transport of very small quantities of materials.

Applications

From the last 25 years, multiple emulsions had been investigated vigorously with revolution in emulsion technology. This system had been explored for several potential applications in cosmetics, separation sciences, pharmaceuticals, food technology, several industrial processes and as drug delivery systems. Various pharmaceutical applications include bioavailability enhancement, taste masking, drug targeting, prolonged delivery of drugs, immobilization of enzymes etc.

(1) Cosmetics

Emulsions are one of the most useful systems in cosmetics and toiletries preparations because most preparations are based either on oil-in-water or water-in-oil emulsions. w/o/w multiple emulsions provide advantage of having the external aqueous phase where any w/o type emulsion can be incorporated in water, thereby overcoming the shortcomings of w/o emulsions. Multiple emulsions have preference over simple emulsions in personal care products because of the slow and controlled release of drugs.  Multiple emulsion based formulations can be used for different purposes like nutritive, moisturizing and protective in cosmetics.35 Long term stable multiple emulsion can overcome the stability problems of emulsions for cosmetic use.36-38 

For increasing stability of multiple emulsions in personal cleansing system, synergistic interaction between the low HLB emulsifier and the high HLB surfactant was investigated by many researchers. These systems produced long term stability in multiple emulsion because of very low interfacial tension at the oil/water interface.39 Recently, a multiple emulsion formulation was developed for the treatment of acne vulgaris. This formulation contained tea tree oil, as an active ingredient, which is a popular antimicrobial agent for the pilosebaceous applications.40 Vitamin C (ascorbic acid), a moisturizing and anti-aging active ingredient is widely used in skin care products. Delivery of this agent through multiple emulsion prevent its degradation against oxidation and also provides better and prolonged release. Slow release characteristic is an additional advantage of this multiple emulsion system for the cosmetic purposes.41

(2) Separation sciences

Multiple emulsions have been explored for engineering sciences and chemistry for the separation of heavy metals (Cr, Cu, Zi, and Ni), hydrocarbons and different compounds. These have been utilized for the separation of contaminant from the waste water of industries.42-44 These have also shown potential in separation of the biological materials (nucleoside, lactic acid).45,46

(3) Pharmaceuticals 

In pharmaceuticals the basic pathway for absorption of drug from multiple emulsion system was hypothesized through intestinal lymphatic system in the form of chyclomicron and lipoproteins. The system either can be absorbed directly through intestinal macrophage or through peyer’s patches or from mesenteric lymph duct in the form of chyclomicron and lipoproteins. Due to intestinal lymphatic absorption of oils present in multiple emulsions, it had also been utilized for modulating drug absorption kinetics i.e prolonged or sustained delivery. Pharmaceutical potential of multiple emulsions has been extensively realized in areas as bioavailability enhancement, drug targeting and prolonged release delivery (i) Multiple emulsions (w/o/w) have been investigated for controlling release of different categories of drugs specially having short half-lives. Partitioning of drugs from water to oil phase and then to external aqueous phase for release in w/o/w multiple emulsions leads to the prolonged delivery of the drug (Table 1) (ii) Increasing bioavailability of drugs having high first pass metabolism: Multiple emulsion increases bioavailability of drugs either by protecting these in physiological, ionic/enzymatic environment in the GIT where otherwise these gets degraded like proteins, peptides or bypassing the hepatic first pass metabolism.47  (iii) Targeting drugs to lymphatics: Multiple emulsion has shown great potential for targeting the cytotoxic drugs (highly toxic drugs) and targeting different kinds of tumors. These have been used as lymphotropic carriers for drug targeting to several organs (Liver, brain etc.) because of its uptake by reticuloendothelial system.48-52 Table 1 gives an overview of the potential of multiple emulsions in the afore mentioned areas.

Table 1. An overview of the potential of multiple emulsions

Category

Drug investigated

Route of administration and/or model used

PROLONGED/CONTROLLED DRUG DELIVERY

Analgesic and antipyretic agents

Antipyrine

4-Aminoantipyrine

In-vitro drug release study53

Diclofenac sodium

In-vitro and in-vivo evaluation in male rabbits54

In-vitro characterization55

In-vitro characterization56

Paracetamol

In-vitro analysis57

Anticancer agents

6-Mercaptopurine

In-vitro and in-vivo antitumor studies in mice (intravenously/intraperitoneally)58

Methotexate

In-vitro characterization59

Cytarabine

In-vitro analysis60

Doxorubicin

In-vitro characterization and tissue distribution studies in rats61

Etoposide

In-vitro analysis62

5-fluorouracil

In-vitro analysis63

Intramuscular administration in rats64

In-vitro release65

Tegafur

In-vitro release66

Antimalarials

Chloroquine

In-vitro release67

Antitubercular agents

 

 

 

Rifampicin

In-vitro characterization68

In-vitro release69

Isoniazid

In-vitro release analysis70

In-vitro release and bioavailability study in healthy volunteers71

Antiasthmatic agents

Salbutamol

In-vitro drug release72

Theophylline

In-vitro release analysis73

Antibiotics

Cefadroxil, Cephradine

In-vitro analysis53

Intravenous administration in rats74

Nitrofunrantoin

Bioavailability study in healthy volunteers75

Antihistaminic

Chlorpheniramine

In-vitro release76

Antimalarial

Chloroquine phosphate

Oral administration77

Peptides

 

Vancomycin

In-vitro characterization10

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In-vitro release and i.v, i.m, i.p administration in rats11

Insulin

In-vitro release73

Oral administration in rats78

Salmon calcitonin

In-vitro and In-vivo evaluation in rats after oral administration79

Miscellaneous

Iodine-131-labelled iodohippuric acid

Intramuscularly to rabbits80

Prednisolone

Ocular  administration into rabbit eye17

Pilocarpine

Intraocular pressure in rabbits eye81

Naltrexone

In-vitro release82

Phenylephrine

In-vitro and in-vivo studies83

Pentazocine

In-vitro drug diffusion studies and oral administration in mice84

BIOAVAILABILITY ENHANCEMENT

Antidiabetic agents

Insulin

In-vivo evaluation85

Intraduodenal administration in rats and gebril86

In-situ in male rats87

In-vitro characterization88

In-situ in male rats89

Anti-fungal agent

Griseofulvin

Healthy human volunteers90

Antitubercular agents

Isoniazid

In-vitro release analysis70

In-vitro release and bioavailability study in healthy volunteers71

Antibiotics

Vancomycin

Orally to male rats91

Nitrofurantoin

Bioavailability study in healthy human volunteers75, 92

TARGETED DRUG DELIVERY

Lymphatic system

5-fluorouracil

Oral administration in rats93

Intratesticular administration94

Iodohippuric acid

In vivo studies95

Bleomycin

Intramuscularly administration to rats96

Isoniazid

Invitro release analysis70

Brain

Rifampicin

Oral and nasal administration to male rats97

Liver

Epirubicin

Intravenous  and  TAE in hepatocellular carcinoma in rats9

Lungs

Rifampicin

In-vitro and in-vivo characterization98

Inflammatory tissue

Diclofenac sodium

In-vitro and in-vivo studies in rats99

(b) Gene library

The use of multiples emulsion has been described for compartmentalization and selection of large gene libraries. The aqueous droplets of the w/o emulsion functions as a cell-like compartment in each of which a single gene is transcribed and translated to give multiple copies of the protein (e.g., an enzyme). While compartmentalization ensures that the gene and the protein it encodes, and the products of the activity of this protein remain linked, it does not directly afford a way of selecting for the desired activity.100

(c) Oxygen substitute

Multiple emulsions had been tried out as a substitute to blood where hemoglobin has been incorporated in the inner phase of emulsion.  A stable hemoglobin (Hb)-in-oil-in-water (Hb/o/w) multiple emulsions simulating red blood cell properties has been reported earlier in which gases (O2 and CO2) are exchanged with hemoglobin. But from the last one decade there is no report for multiple emulsion investigated for this purpose. Challenges in this are the artificiality, immune response and the questionable in-vivo compatibility of chemicals.101-103

(d) Taste masking

Taste masking of bitter drugs like chloroquine has already been investigated as one of major pharmaceutical applications of multiple emulsions. Multiple emulsions of chloroquine, an antimalarial agent has been successfully prepared and had been found to mask the bitter taste efficiently.77,104,105 Taste making can be achieved by incorporating drugs in inner aqueous phase of w/o/w multiple emulsion which is being surrounded by oil layer masking the taste. Taste masking of chlorpromazine, an antipsychotic drug has also been reported by multiple emulsions.106

(e) Enzyme immobilization

Enzyme immobilization technique involves the entrapment of enzymes, which catalyze several reactions. Reports of using multiple emulsions for enzyme immobilization goes back to 1972 where hydrocarbon based multiple emulsion were used to entrap urease enzyme for kidney diseases.107 Later same worker immobilized enzymes and whole cell from M. denitrificans for waste water treatment.108,109 Presently this technique has been established as a tool for immobilization of various enzymes, proteins, amino acids etc in biotechnology. Immobilized alcohol dehydrogenase has been utilized for the conversion of alcohol to acetaldehyde for industrial use.110 Like wise Makryalese and coworkers111 carried out conversion of ketoisocaproate to L-Leucine by L-Leucine dehydrogenase. Enzymatic production of aminoacid (L-Phenyl alanine) from immobilized chymotrypsin was reported by Scheper et al.112 Similarly Iso et al113 used immobilized lipase enzyme for the hydrolysis of fatty acids.

(f) Drug over dosage treatment/detoxification

Liquid membrane system had been efficaciously used for the drug overdosage treatment as early as 1978.114 This system could be utilized for the overdosage treatment by utilizing the difference in the pH in different compartments of multiple emulsions, which affects the ionization behavior of the drug. These have been utilized for acidic drug overdosage treatment like barbiturates. In these emulsions, the inner aqueous phase of emulsion has the basic buffer and when emulsion is taken orally, acidic pH of the stomach acts as an external aqueous phase. In the acidic phase barbiturate remains mainly in unionized form which transfers through oil membrane into inner aqueous phase and gets ionized. Ionized drug has less affinity to cross the oil membrane thereby getting entrapped. Thus, entrapping excess drug in multiple emulsion cures over dosage. Like wise quinine sulfate overdosage treatment has been reported.115 Detoxification of blood by multiple emulsions have also been reported.116,117

(g) Topical applications

Multiple emulsions slowly release their contents in comparison to solutions because of the three-phase system, therefore is of immense use in topical applications.118 Bonina et al119 developed a three-phase emulsion containing model compounds testosterone, caffeine and tritiated water for topical use. They also investigated the effect of Fomblin on percutaneous absorption. Fomblin did not affect flux of caffeine while decreased the percutaneous absorption of testosterone but increased water permeation Raynal S et al120 prepared a topical w/o/w emulsion containing sodium lactate (moisturizing agent) in inner phase; spironolactone (anti acne agent) in intermediate oily phase; and chlorhexidine digluconate (antibacterial) in outer phase. Ferreira and coworkers121-123 developed w/o/w multiple emulsion carrying metronidazole and glucose and compared their percutaneous release with w/o and o/w emulsions. Absorption of metronidazole was similar from w/o/w and o/w emulsions and was on lower side from w/o emulsion whereas in case of glucose absorption was in following order o/w>w/o/w>w/o Multiple emulsion has been employed to increase stability of ascorbic acid for topical purpose.41,124 Laugel and coworkers125,126 have developed multiple emulsions for dihydralazine and hydrocortisone as well. A successful w/o/w multiple emulsion preparation containing lactic acid in the internal aqueous phase, octadecylamine in oily phase and benzalkonium chloride in the external aqueous phase was developed for vaginal application against three microbial strains (Escherichia coli, Staphylococcus aureus and Candida albicans).127 Later the efficacy and antimicrobial spectrum of this formultion was enhanced by incorporationg chlorhexidine digluconate to the internal aqueous phase of the multiple emulsions.128 A stable w/o/w multiple emulsions was developed with poloxamine 908 as a hydrophilic surfactant  for topical purposes.129

(h) Technique for microsphere/microcapsule preparation

Multiple emulsion solvent evaporation method is now one of the well-recognized methods for the preparation of microspheres, nanospheres, nanoparticles, microcapsules etc. In this method, multiple emulsion formation is an intermediate step which finally gives rise to the final product. Bodmeier et al130 employed a novel technique, water in oil in oil double emulsion solvent diffusion for encapsulation of theophylline, propranolol, acetaminophen and tacrine(hydrophilic drugs). Also the microparticles of pseudoephedrine were successfully developed by the previous authors by a multiple emulsion-melt dispersion technique with encapsulation efficiencies of more than 80%.131 Microencapsulation of different categories of drugs like enzymes, hormones, peptides, synthetic drugs have been reported. Different polymers (ethylcellulose, eudragit, polylactic acid, polyglycolic acid etc.) have been employed on the basis of the nature of drug and intended properties of microcapsules. Multiple emulsion had been extensively used as intermediate step for encapsulating many drugs like sulfadiazine,132 salbutamol sulphate,133 retinol,134 leuprolide acetate,135 lysozyme,136 diclofenac sodium,137 metformin138 and PTSA.139

Multiple emulsions have been used to prepare three kinds of hepatitis B surface antigen (HBsAg)-poly (d, l)-lactide-co-glicolide acid (PLGA) microspheres. These microspheres showed greater antibody response in mice in comparison to the conventional aluminum-adjuvant vaccine and thus hold promise for controlled delivery of a vaccine.140 Like wise tetanus toxoid loaded polylactic acid particles were prepared by double emulsion technique. These tetanus toxoid polymer particles elicited high and sustained antibody titers after intramuscular immunization.141 Prabha et al142 prepared nanoparticle containing plasmid DNA which carry wild p53 gene using a multiple-emulsion-solvent evaporation technique. This formulation resulted in sustained antiproliferative activity against breast cancer cells where otherwise repeated delivery of gene is required. Recently this technique has been utilized for efficiently encapsulating DNA for preparing polymeric nanoparticles with intended characteristics and hence can be a potential tool in era of nanotechnology in future.143

(i) Vaccine/vaccine adjuvant

The use of w/o/w multiple emulsion as a new form of adjuvant for antigen was first reported by Herbert.144 These emulsions elicited better immune response than antigen alone.  Rishendra and Jaiswal145 developed a multiple emulsion vaccine against Pasteurella multocida infection in cattle. This vaccine contributed both humoral as well as cell-mediated immune responses in protection against the infection. It was concluded that this multiple emulsion based vaccine can be successfully used in the effective control of haemor-rhagic septicaemia. Recently, multiple water-in-oil-in-water (w/o/w) emulsion formulations, containing influenza virus surface antigen hemagglutinin were prepared and were characterized in-vitro and in-vivo in wistar albino rats. SDS-PAGE technique was used for evaluating hemagglutinin and in vitro release of antigen respectively. Results suggested that multiple emulsion formulations carrying influenza antigen have advantage over conventional preparation and can be effectively used as one of the vaccine delivery system with adjuvant properties. In an another report by the same researchers they concluded that multiple emulsion and nanoparticle formulations containing influenza virus surface antigen Hemagglutinin were more effective in eliciting an immune response in rats than the conventional vaccine.146,147

Conclusion

Availability of newer emulsion technologies have greatly helped in exploring liquid membrane systems extensively for both oral as well as parenteral applications. This system is equally suitable for hydrophilic and lipophilic drugs. With an inherent versatility in carrier design they have shown promise for bioavailability enhancement, prolonged release, taste masking, detoxification, drug targeting etc. Stability of liquid membranes still remains a great challenge and several approaches have been tried out to overcome this caveat. Given the pace of the ongoing research, we can very soon expect various liquid membrane systems with appropriate stability for various potential pharmaceuticals applications. 

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About Authors:

Azhar_Yaqoob_Khan.jpg

Azhar Y Khan

Research Scholar, Dept of Pharmaceutical Medicine, Faculty of Pharmacy, Jamia Hamdard, New Delhi
Email: azharykhan@gmail.com, Ph no; 011-26059688-Extn-5654

For correspondence:

Sushama Talegaonkar

Dr. Sushama Talegaonkar

Senior Lecturer, Dept of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard,New Delhi
Email: stalegaonkar@jamiahamdard.ac.in, Ph no; 011-26059688-Extn-5654
Research Interest: Nanotechnology based drug delivery systems, Targeted drug delivery system.

R.K.Khar M.Pharm, Ph.D
Dept of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi
Email: rkkhar@jamiahamdard.ac.in, Ph no; 011-26059688-Extn-5605

Dr. Farhan Jaless Ahmed
Dept of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi

Dr. Zeenat Iqbal
Dept of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi

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