Mr.Santosh Payghan

The delivery of poorly water-soluble drugs has been the subject of much research, as approximately 40% of new chemical entities are hydrophobic in nature. One area in which published literature is lacking is the field of non-aqueous emulsions.

This review gives a conceptual idea about non-aqueous system. Non-aqueous systems are well known as solvents for drugs, suspension vehicles, oleogels, soft gelatin or magnoresponsive drug delivery system. It provides reservoir vehicles for transdermal systems and controlled drug delivery systems or hydrolytically unstable drugs.

Introduction:

An emulsion is a system in which one fluid is dispersed in another with which it is immiscible. Macroscopic separation of the phases is prevented by the addition of a suitable surfactant. In the vast majority of emulsion research, one of the liquid phase is water⁵.

Emulsions with no aqueous phase (anhydrous, non-aqueous, oil-in-oil emulsions, oil-polar solvent) have had relatively scant attention, where non-aqueous systems are well known as solvents for drugs, suspension vehicles, and oleogels ²².However Nonaqueous emulsions could replace regular aqueous emulsions wherever the presence of water is undesirable; for example, in cleaning systems that are sensitive to formation of rust such as engines and other mechanical systems, or for doing sol–gel processes with hydrolysable metal alkoxides in organized media in a controlled way ^10,15,16,17.

Non-aqueous emulsions may be of pharmaceutical or cosmetic value if they are composed primarily of edible, non-toxic ingredients and can be formulated to exhibit a wide range of physical properties. Some possible uses might be as topical application bases for dermatological, particularly for labile drugs, as emollient bases for cosmetic preparations, or as nutrient preparations^23,33. Yet it uses as drug reservoirs, as well as templates for the preparation of microspheres, nanoparticles and silicate microstructures^{16, 17,27,30,31}.

There are few reports in the literature on formulation of non-aqueous emulsion. After the study of two non aqueous (oil phases) or polar solvent-oil phases it can be concluded that, there are no guidelines for stabilization of two immiscible non polar oils or polar solvent-oil phases, because HLB systems do not hold this systems. Thus there are some challenges in producing stable non-aqueous emulsions, which might be useful in formulating base for soft gelatin or magnoresponsive drug delivery system or hydrolytically unstable drugs or to provide reservoir vehicles for transdermal systems and controlled drug delivery systems^{23, 34}.

Noteworthy Contribution:

There is not only a lack of data relating to the formulation of non-aqueous emulsions, but there are relatively few publications on the subject. The emulsifying effects of several ionic and non-ionic surfactants on the non-aqueous, binary system of glycerin and olive oil have been reported, the anionic agents, dioctyl sodium sulfosuccinate, diamyl sodium sulfosuccinate and the calcium stearate failed to produce stable emulsion under the condition of this studies²¹, but some anionic agents were effective in producing emulsification of glycerin and olive oil. Tetra-sodium – N – (1,2-dicarboxyethyl) – N – octadecylsulfosuccinate, sodium lauryl ether sulphate, and sodium lauryl sulphate produced stable, some what opaque preparation²¹. The amines, 2 – amino – 2 – methyl – 1,3 – propandiol, trisamminomethane, ethanolamine, triethanolamine and ammonia gas at very low concentration, formed saponification product, which results in clear, stable emulsion²¹. The cationic agents, benzalkonium chloride and lauryltrimethyl ammonium bromide, like wise failed to stabilize the system. but also three cationic agents, cetyl pyridinium chloride, stearyl trimethyl ammonium chloride and the stearyl dimethyl benzyl ammonium chloride produce stable emulsion of this system²¹. Several non-ionic agents,  sorbitan monolaurate (S-20), sorbitan monopalmitate (S-40), S-60, sorbitan monooleate (S-80), sorbitan sesquioleate (S-83), sorbitan trioleate (S-85), GMS-165,GMS- 169, Polyoxyethylene sorbitan monolaurate (PS-20) , Polyoxyethylene sorbitan monopalmitate (PS-40), PS-60, and Polyoxyethylene sorbitan monooleate (PS-80), POL-30 and 35, POS 45 and 52, Sucrose Dipalmitate (DPM 600), octakis (2-hydroxypropyl) sucrose (OHS 80) including were tested for their capacity to emulsify the non aqueous system of glycerin and oil. Blends of Arlacels and polysorbates at various HLB values also were prepared and tested. Stable emulsions resulted from the use of several of these agents and combinations ^{12,13,14,15,20,25,26}.

Reichmann.K.W and Petersen R.V also studied the effect of temperature on non-aqueous emulsions. Some authors have used non-aqueous emulsions in the preparation of Nanoparticle or as templates in the formation of silicate microstructures, usually without providing details of formulation issues³⁰

Imhof.A.developed stable concentrated oil-in-formamide and oil-in- sulfoxide emulsions using commercially available nonionic surfactants. Several other polar liquids are turned out not to produce stable nonaqueous emulsions with these surfactants. It is unclear,  exactly which combination of molecular properties determines the emulsifying capacity, but hydrogen bonding clearly plays a more important role than polarity. The most effective surfactants were the triblock copolymers PEO–PPO–PEO. Owing to their relatively large size they could stabilize formamide and dimethyl sulfoxide  emulsions against breaking practically indefinitely ^15,16,17.

Ostwald ripening was shown to be a very important factor in the stability of these nonaqueous emulsions, which is considerably faster than in aqueous systems because of the higher (though still low) solubility of oils in nonaqueous polar solvents. Ostwald ripening could be completely arrested by dissolving a compound (1% ) in the oil with an extremely low solubility in the continuous phase. While more recently Cameron and Sherrington have reported emulsions of petroleum ether in formamide, DMF and DMSO ⁶. This is necessary in order to obtain completely stable emulsions^{15, 16}.

Sakthivel.T.et.al  formulate anhydrous emulsions, reporting on dodecane in polyethylene glycol systems stabilized by sorbitan trioleate³³ and also emulsions of alkanes in formamide emulsified with polysorbate 20 ³⁴. Emulsions with polar continuous phase such as DMSO, DMF and formamide have more similarity with aqueous systems than systems comprising two non-polar oils, which present greater challenges ^15,16, still hydrocarbons and formamide are pharmaceutically unsuitable materials. Sakthivel.T. et.al also report on castor oil-in-silicone oil (polydimethylsiloxane and cyclopentasiloxane) emulsions,advantage of this non-aqueous systems is that the properties of both phases can often be manipulated, for example by varying the molecular weight of oligomeric or polymeric liquids in one of the component phases.

Emulsions of castor oil-in-silicone oils of varying viscosity stabilized by the octylphenylpoly (10) oxyethylene ether (Triton-X-100) had been previously been reported ^33,34, optimization of the viscosity of the silicone oils was determined and emulsions comprised of castor oil in silicone oil of different viscosities have also been used as models to study rheological behaviors in an electric field ^6,10.

Orawan Suitthimeathegorn.et.al, demonstrated that the administration of ³H-dexamethasone in a Castor oil/Silicone oil non-aqueous emulsion showed slower absorption and distribution to various organs in the rat following intramuscular injection compared to an o/w formulation but did not bring about very prolonged plasma levels. One advantage, however, may be that the Castor oil/Silicone oil non-aqueous emulsions can be used as anhydrous vehicles where the presence of water is undesirable ²⁴.

Biological Issues In The Selection Of Non-Aqueous Systems:

Very few biopharmaceutical studies have been performed with Non-Aqueous Systems, and there is a need for more comparative studies, particularly against solid dosage forms. However, it is worth speculating at this stage on the issues, which will influence the absorption from Non-Aqueous Systems. In case of oral drug delivery the rate of gastric emptying of Non-Aqueous Systems is similar to solutions, so that they are particularly useful where rapid onset of action is desirable. Conversely if the therapeutic index of the drug is low, the rapid onset and accompanying high T_max may lead to undesirable side effects. With regard to bioavailability there are differences between formulations, which contain water-soluble surfactants and those, which do not. The former systems may produce emulsions or micellar solutions with lower capacity for solubilization of drugs, which may result in precipitation of drugs in the gut. Non-Aqueous Systems formed with relatively hydrophobic surfactants (HLB < 12) such as Tween 85 or Tagat TO, which do not migrate into the polar phase, tend to have lower solvent capacities for drugs unless log P (drug) > 4. Another important consideration, though, will be the toxicity of the surfactants, particularly if the indication for the therapy is chronic. If the drug is sufficiently oil soluble a good case can be made for avoiding non aqueous sysyems completely and formulating the drug as a simple triglyceride solution, making use of lipolysis to aid dispersion of the formulation.

Fundamentals Of Non-Aqueous Emulsion:

The selection of solvents for formulating nonaqueous emulsion is of importance. The development of a theoretical basis for the selection of the solvent and predicting their respective miscibility and behaviour of a surfactant is required ^5,6. The selection of the two phases depends largely on the polarity of the solvents. Stable oil in formamide and oil in polyethylene glycol emulsions could be prepared using commercially available non-ionic surfactants. However, it is relatively difficult to predict the applicability of other polar liquids to serve as the continuous phase. It is still unclear which combination of molecular properties can be used to predict with any certainty a stable system formed with a given surfactant,  nevertheless, hydrogen bonding appears to play a pivotal role in determining the stability. However, formamide is closest to water in terms of hydrogen bonding and dielectric constant and was chosen as the external phase ¹⁵.

Two basic strategies could be considered when searching for stable non-aqueous emulsions.

(a)One is to design surfactants having two incompatible blocks, each of which is selectively soluble in either of the immiscible liquids. For example, diblock copolymers of polystyrene and polyisoprene were able to stabilise DMF and hexane emulsions for almost 24 h ^15,16.

(b)The other approach is to search for a suitable oil-immiscible polar liquid that can substantially replace water using existing surfactants. For example Non-ionic surfactants with HLB numbers around 12 were found to stabilize oils dispersed in formamide^15,16.

The first approach has, of course, the drawback of necessitating the specific design and characterization of a new surfactant for each combination of liquids^5,6. A liquid capable of replacing water in an emulsion should have an appreciable polarity to make it immiscible with oils and to make it a good solvent for the solvophilic part of the surfactant molecules. Hydrogen bonding in the polar liquid is expected to play a role in solvating both ionic and non-ionic surfactants, and in the formation of a hydrogen-bonded network in the liquid itself. In each nonaqueous surfactant system the concept of hydrophilicity should be replaced by solvophilicity, thus defining a new scale, which incorporates interactions specific to that solvent. ^15,16

Dispersed Phase	Continuous Phase	Surfactant/Combination of surfactant	Authors
Olive oil Dodecane Dodecane Liquid crystals* Silicone oils Dodecane Castor oil Dodecane   Castor oil     Castor oil     Dimethicone Non -aqueous polar solvent Propylene glycol Formamide         Formamide,Ethyle-neglycol,1,2-prop-ylene glycol and glycerol in combi-ation with p-xylene and n-pentanol Petroleum ether     Non-aqueous polar solvent Polyoxyethylene Glycol     Castor oil	Glycerin Formamide DMSO Silicone oil liquid crystals Formamide Silicone oil Poly oxyethy-lene glycol Dimethicone     Cyclopenta siloxane   Castor oil Silicone oil   Fatty ester Monomers         -------           Formamide,N,N -dimethyl formamide, dimethyl sulfoxide Silicone Elastomer Thermoplastic elastomer ** Silicone oil/water	Anionic, Cationic, Non-ionic Non-ionic Non-ionic Non-ionic   Polysorbate 20,40,60,80 Non-ionic Non-ionic   Silicone surfactant (cyclome- thicone/di methicone copo- lyols) Silicone surfactant (cyclomethi-cone /dimethicone copolyols) Non-ionic Anionic and Non-ionic   Lecithin AOT(bis(2-ethylhexyl) Sulfosuccinate Na salt), sodium bromide (NaBr), and either of the mono mershexyl methacrylate Anionic, Cationic, Non-ionic            Polymeric and non – polymeric non-ionic surfactants     --------   --------   Silicone surfactant (cyclomethicone/dimethic-one copolyols)	Hamill.et.al (1964,1965,1966) Imhof,Pine (1997) Imhof,Pine (1997) Loudent, Richard., et.al (2000)   Sakthivel.T et.al (2001) Jaitely.V, Sakthivel, et.al (2004) Sakthivel, Van, Florence (1999)   Suitthimeathegorn., et.al (2005)       Suitthimeathegorn, jaitley (2005)   Sakthivel,et.al (2005) Lin.et al US Patent 6,080,394   Geyer, et al.US Patent 5,110,606 Schubert, K.-V.Lusvardi, K.M.,Kaler, E.W. (1996)       Dorfler, H.-D., Nestler, E. Tenside, (1990)         Neil R. Cameron and David C. Sherrington (1996) Powell, et al. US Patent number 6,271,295 Riess., et.al (2004)   Suitthimeathegorn, Florence (2007)

Table 1: Formulation Of Non-Aqueous Emulsion With Different Composition By Different Authors.

*Mixture of cynobiphenyl and cyanoterphernyl molecules

** Dissolved in methycyclohexane ,which is then evaporated

Requirments Of Non-Aqueous Emulsion:

Non-aqueous polar solvent:

While the term non-aqueous polar solvent is intended to include solvents generally, when the emulsions are intended for personal care application, then the non-aqueous polar solvent should be one recognized as being pharmaceutically acceptable. In a preferred embodiment, polar liquid that exhibits a dipole moment of from 0.9 to 4.5 should be selected. Representative of some pharmaceutically acceptable non-aqueous polar solvents, which can be used, for example, in a highly preferred embodiment polar hydroxylic liquids for example, one or more of alcohols, glycols, polyhydric alcohols polymeric glycols and mixtures thereof. Preferably, the polar liquid contains an (C.sub.1 -C.sub.12) monohydroxy alcohol, such as ethanol, propyl alcohol and iso-propyl alcohol, a (C.sub.2 -C.sub.12) diols and triols , such as propylene glycol, dipropylene glycol, tripropylene glycol, butylene glycol, iso-butylene glycol, 2- and methyl-3-propane diol, a polyhydric alcohol, such as glycerin erythritol and sorbitol, or a polymeric glycol, such as polyethylene glycol, polypropylene glycol mono alkyl ethers and polyoxyalkylene copolymers. In a highly preferred embodiment, the polar liquid is selected from ethanol, propyl alcohol, iso-propyl alcohol, propylene glycol, dipropylene glycol, tripropylene glycol, butylene glycol, iso-butylene glycol, 2-methyl-3-propane diol, glycerin, erythritol sorbitol, polyethylene glycol, polypropylene glycol mono alkyl ethers, polyoxyalkylene copolymers, glycerol esters such as glyceryl triacetate (triacetin), glyceryl tripropionate (tripropionin), and glyceryl tributyrate (tributyrin) etc.^{9, 28,29}

Oil phase:

(i)Volatile polydimethyl siloxanes such as hexamethyldisiloxane, octamethyltrisiloxane, and decamethylcyclopentasiloxane,

(ii)Medium Chain Triglycerides, Fatty Ester (Ethyl palmitate) etc.

(iii)Nonvolatile polydimethylsiloxanes having a viscosity generally in the range of about 5 to about 1,000 centistokes (mm² /s), and (i) fragrances such as musk and myrrh.

(iv)Organic oils such as natural oils derived from animal, vegetable, or mineral sources, are also suitable. Modern cosmetic oils, for example, are most representative, and among common organic oils known to be safe for cosmetic purposes are almond oil, apricot kernel oil, avocado oil, cacao butter (theobroma oil), carrot seed oil, castor oil, citrus seed oil, coconut oil, corn oil, cottonseed oil, cucumber oil, egg oil, jojoba oil, lanolin oil, linseed oil, mineral oil, mink oil, olive oil, palm kernel oil, peach kernel oil, peanut oil, rapeseed oil, safflower oil, sesame oil, shark liver oil, soybean oil, sunflower seed oil, sweet almond oil, tallow (beef) oil, tallow (mutton) oil, turtle oil, vegetable oil, whale oil, and wheat germ oil. ^{9, 28,29}

Surfactant:

In a preferred embodiment, the emulsion comprises one or more emulsifying agents. A range of industrial surfactants were screened using subjective visual assessment for their ability to form non-aqueous systems with medium-chain and long-chain triglycerides. The most efficient systems were formed by surfactants with predominantly unsaturated acyl chains, silicone-containing emulsifying agents, emulsifying agents derived from sorbitan compounds and emulsifying agents derived from fatty alcohols and polymeric emulsifiers. Amongst these the most efficient were oleates with HLB values of approximately 11. Sorbitan esters or ethoxylated triglycerides (e.g. Tagat TO) were usually more efficient than fatty acid ethoxylates, probably because the latter are more polydisperse since they usually contain mono and di-esters. A range of related excipients have been used to formulate non aqueous systems by other authors [A list of materials (Table 1) and some example of formulations (Table 2,3,4,5)] is given below. ^{9, 28,29,37}

Table 2: Ampholytic And Zwitterionnic Type Of Surfactants Used In Non-Aqueous Emulsion

Ampholytic	Zwitterionnic
3-[N,N—Dimethyl (3-palmitoyl  aminopropyl) ammonio]-propane sulfonate N-Dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate Sodium 2,3-dimercapto Propane sulfonate monohydrate	3-(N,N-Dimethyloctylammonio) propane sulfonate 3-(N,N-Dimethyl palmityl ammino) propane sulfonate 3-(Decyl dimethylammonio) ­propane­ sulfonate N-Dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate N-Dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate

Table 3: Anionic Type Of Surfactants Used In Non-Aqueous Emulsion

Anionic

1-Octanesulfonic acid sodium salt 1-Octanesulfonic acid sodium salt Chenodeoxy cholic acid Cholic acid from ox or sheep bile. Dehydro-cholic acid Deoxycholic acid Docusate sodium salt Glycocholic acid hydrate Glycodeoxy cholic acid monohydrate Glycolithocholic acid ethyl ester Lithium 3,5-diiodosalicylate Lithium dodecyl sulfate Lithium dodecyl sulfate Lithium dodecyl sulfate N,N-Dimethyl dodecyl amine N-oxide N-Lauroyl sarcos-ine sodium salt N-Lauroyl sarcos-ine sodium salt N-Lauroyl sarcos-ine Niaprof Sodium 1-butane sulfonate Sodium 1-decane sulfonate Sodium 1-decane sulfonate Sodium-1-dodecane sulfonate Sodium 1-heptane sulfonate Sodium 1-heptanesulfonate Sodium 1-Nonane sulfonate

Sodium deoxy cholate monohydrate Sodium deoxy cholate Sodium dodecyl sulfate Sodium dodecyl sulfate Sodium dodecyl sulfate Sodium dodecyl benzene sulfonate Sodium glyco cheno deoxy cholate Sodium glyco cholate hydrate Sodium hexane sulfonate Sodium hexane sulfonate Sodium octyl sulfate Sodium pentane sulfonate Sodium pentane sulfonate Sodium tauro chenodeoxy cholate Sodium tauro deoxy cholate hydrate Sodium glycodeoxy cholate Sodium tauro deoxy cholate hydrate Sodium taurolitho cholate Sodium taurourso deoxy cholate ~90% Taurocholic acid sodium salt hydrate Tauro lithocholic acid 3-sulfate disodium salt Tetrabutylammonium perchlorate dodecyl sulfate Sodium chenodeoxyCholate Sodium cholate hydrate Sodium cholate hydrate from ox or sheep bile. Sodium 1-propane sulfonate monohydrate

Table 4: Cationic Type Of Surfactants Used In Non-Aqueous Emulsion

Cationic

Alkyl tri methyl ammonium bromide Amprolium hydrochloride Benzalkonium chloride Benzethonium chloride Benzethonium hydroxide Benzyl dimethyl hexadecyl ammonium chloride Benzy dimethyl tetradecyl ammonium chloride Denatonium benzoate Benzyldodecyldimethylammonium bromide Dimethyldioctadecylammonium bromide Dodecyl ethyl dimethyl ammonium bromide Dodecyl trimethyl ammonium bromide Dodecyl trimethyl ammonium bromide Ethylhexadecyl dimethyl ammonium bromide Ethyl hexadecyl dimethyl ammonium bromide Girard’s reagentT 99% Hexa decyl pyridinium bromide Hexadecyl pyridinium chloride monohydrate Hexadecylpyridinium chloride monohydrate Hexadecyl trimethyl ammonium bromide Hexadecyl trimethyl ammonium bromide Hexadecyl trimethyl ammonium p-toluene sulfonate Methylbenzetho- nium chloride Myristyltrimethylammonium bromide N,N′,N′-Polyoxy ethylene(10)-N-tallow-1,3-diamino propane liquid Oxyphenonium bromide Tetra heptyl ammonium bromide Tetrakis(decyl)ammonium bromide Thonzonium bromide Saponin

4-Nonyl phenoxy polyglycidyl ether 6-Cyclohexyl hexyl β-D-maltoside Bis (polyethylene glycol Bis[imidaz-oyl carbonyl]) Brij 30,35,56,72,97,58, Chenodeoxy cholic acid di-acetate Methyl ester Cremophor Cyclohexylmethyl β-D-maltoside Decaethylene glycol mono­dodecyl ether Decyl β-D-glucopyranoside Heptaethylene glycol monohexa decyl ether Hexaethylene glycol monodecyl ether Hexaethylene glycol mono- dodecyl ether Hexaethylene glycol mono dodecyl ether Semisolid Hexaethylene glycol mono hexadecyl ether Hexaethylene glycol mono hexadecyl ether Methoxy polyethylene glycol Methyl 6-O-(N-heptylcarbamo- yl)-α-D-gluco pyranoside Methyl 6-O-(N-heptyl carbam- oyl)-α-D-gluco pyranoside N,N-Dimethyloctadecylamine N-oxide N-Decanoyl-N-methyl glucamine N-Nonanoyl-N-methyl glucamine Nonidet P 40 Octaethylene glycol monoocta decyl ether Octaethylene glycol monotetra decyl ether Octaethylene glycol monotetra decyl ether Octyl β-D-1-thiogluco pyranoside Octyl β-D-lucopyranoside Pentaethylene glycol mono decyl ether Pentaethylene glycol mono dodecyl ether Pentaethylene glycol monodo decyl ether Pentaethylene glycol mono hexa decyl ether Pentaethylene glycol mono hexyl ether

Table 5: Non-Ionic Type Of Surfactants Used In Non-Aqueous Emulsion

Non-inonic

Ethylene glycol Mono decyl ether Ethylene glycol mono dodecyl ether Ethylene glycol mono hexa decyl ether Ethylene glycol monohexyl ether Ethylene glycol monoocta decyl ether Ethylene glycol monooctyl ether Ethylene glycol mono pentyl ether Glucopone 215,600 CS UP and 600,650 EC Diethylene glycol mono decyl ether Diethylene glycol mono dodecyl ether Diethylene glycol monohexadecyl ether n-Dodecyl β-D-glucopyranoside n-Dodecyl β-D-maltoside n-Heptyl β-D-glucopyranoside n-Heptyl β-D-thiogluco pyranoside n-Hexadecyl β-D-maltoside n-Undecyl β-D-glucopyranoside Tetraethylene glycol monohexa decyl ether N-Nonanoyl-N-methylglucamine N-Nonanoyl-N-methylglucamine N-Octanoyl-β-D-glucosylamine Poly (ethylene glycol) diglycidyl ether Polyoxyethylene (20) sorbitan monolaurate Polyoxyethylene 10 tridecyl ether Polyoxyethylene 100 stearate Polyoxyethylene 20 oleyl ether Polyoxyethylene 40 stearate Polyoxyethylene 50 stearate Poly oxyethylene 80 stearate Poly oxyethylene 25

Diethylene glycol mono hexyl ether Diethylene glycol mono octyl ether Diethylene glycol mono pentyl ether Diethylene glycol mono tetradecyl ether Heptaethylene glycol mono decyl ether Heptaethylene glycol mono do decyl ether Heptaethylene glycol mono dodecyl ether Decyl β-D-maltopyranoside Decyl-β-D-1-thiogluco pyranoside Decyl-β-D-1-thiomalto Pyranoside Triton CF 10, N-57, 60,X-100, 207,45,305,405. Digitonin Digitoxigenin Dimethyl decyl phosphine oxide Dodecyl dimethyl phosphine oxide n-Dodecyl α-D-maltoside Hexaethylene glycol mono octa decyl ether Hexaethylene glycol monoocta decyl ether Tetraethylene glycol mono dodecyl ether N-Octanoyl-N-methylglucamine Pentaethylene glycol monooctyl ether Pentaethylene glycol monotetra decyl ether Tergitol NP-9 Sucrose mono decanoate Sucrose mono laurate Tween (Polysorbate) 20,21,40, 60,61,65,80,81,85, Span 20,40,60, 65,80,83,85, propylene glycol stearate

Application And Utility

Magnetic Systems:

Incorporation of magnetite nanoparticles into the disperse phase of these oil-in-oil emulsions has allowed control of the flow of droplets of the phase in capillaries, important in microfluidic systems and also in the design of pulsatile drug release systems.^{7, 10,22,38} Magneto- and electrorheological systems are of increasing interest in controlling the properties of delivery devices.

Controlled Release Vehicle:

Non-aqueous emulsions have potential as vehicles for lipophilic drugs and potential for controlled delivery. ³H-DHEA, a highly lipophilic molecule, was added to the internal phase of the emulsion and the radioactivity released in the dialysing medium of distilled water was measured. The release was observed to follow first-order release kinetics²³. Certain literature showed stable anhydrous emulsions of castor oil and silicone oil. The significant factor in the stabilization of the emulsion was the solubility of the surfactants in the continuous phase, lowering of interfacial tension being not in itself sufficient. As there are no guidelines for the selection of surfactants to stabilize two immiscible non-polar oils still study is continuing for a wider range of non-aqueous systems to develop a better understanding of stabilization. Perhaps an analogue of HLB, a lipophile (1)-lipophile (2) balance (L1L2B) may be used to predict surfactant choice²³.

Capsules:

The delivery of poorly water-soluble drugs has been the subject of much research, as approximately 40%of new chemical entities are hydrophobic in nature. One area in which published literature is lacking is the field of non-aqueous emulsions filled into capsules, still some researchers have used polyethylene glycol (PEG) as a continuous phase for such emulsions ^1,2,3 The nature of this emulsion will allow capsule filling at a later stage and it can be fill into hard gelatin as well as soft gelatin capsules. It has been suggested that these liquid systems can be administered in gelatin capsules and subsequently result in the formation of a fine emulsion within the gastric space. This process may favourably influence the Bioavailability of lipophilic drugs or help to avoid the irritancy which can be caused by high concentration of certain drugs². Non-aqueous emulsion is inert to the capsule shells and did not compromise the seal of these systems over an extended period of time^{11, 26}.

Cosmetic Preparations:

While emulsions and multiple emulsions according to the present invention are useful in any application, which can benefit from the attributes of an organosilicon material, they are primarily intended for use in personal care. Thus, they can be used alone or combined with cosmetic ingredients to form a number of over-the-counter (OTC) personal care products. For example, they are useful as carriers in antiperspirants and deodorants. They are lubricious and can improve the properties of skin creams, skin care lotions, moisturizers, facial treatments such as acne or wrinkle removers, personal and facial cleansers, bath oils, perfumes, colognes, sachets, sunscreens, pre-shave and after-shave lotions, liquid soaps, shaving soaps, and shaving lathers. They can be used in hair shampoos, hair conditioners, hair sprays, mousses, permanents, depilatories, and cuticle coats, to enhance gloss, and provide conditioning benefits.^9,28,29 The emulsions and multiple emulsions can function as leveling and spreading agents for pigments in make-ups, color cosmetics, foundations, blushes, lipsticks, lip balms, eyeliners, mascaras, oil removers, color cosmetic removers, and powders. When incorporated into sticks, gels, lotions, aerosols, and roll-ons, the emulsions and multiple emulsions can impart a dry and silky-smooth feel ^9,18,29.

Multiple Systems:

Having formed oil-in-oil systems and polar solvent-oil systems, it follows that multiple systems can also be formulated. Either p.s/o/p.s or o/p.s/o  for polar solvent –oil system and o₁/o₂/o₁ systems or o₁/o₂/w for oil in oil system formulations are possible, examples of both are shown in Figure 1 ^22,28,29

Figure 1: Photomicrographs of two multiple emulsions (a) is a non aqueous emulsion, an o/o/o emulsion and (b) is an o/o/w emulsion.(a). is a formulation of castor oil-in-silicone oil-castor oil. (b) is a multiple emulsion of castor oil-in-silicone oil-in water.

Miscellaneous:

The emulsions are also capable of functioning as carriers for pharmaceuticals, biocides, herbicides, pesticides, and other biologically active substances; and they have utility as additives for cellulosic or synthetic nonwoven carrier substrates used in wet-like cleansing wipes such as wet-wipes, tissues, and towels, marketed generally for personal hygiene and household cleaning tasks ^5,19,31,38

Conclusion:

The delivery of poorly water-soluble drugs has been the subject of much research, as approximately 40% of new chemical entities are hydrophobic in nature. One area in which published literature is lacking is the field of non-aqueous emulsions. This review gives a conceptual idea about non-aqueous system, still a challenge remains to take the formulation beyond the semi-empirical by developing L₁L_2B or Polar solvent/Oil Balance systems, probably based on the solubility parameters of the oil phases and the surfactant stabilizers. Well-stabilized systems will, we predict, find uses in controlled release. We are about to begin studies on formulation, drug release from intramuscular and subcutaneous depots of these non-aqueous systems.

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About Authors:

Mr. Santosh Payghan
For Correspondence
Lecturer, Dept. Of Pharmaceutics, Mandsaur Institute of Pharmacy, Rewas-Dewda Road, Mandsaur-458001, M.P
E-mail: santosh14july@rediffmail.com; Phone: +919826953642.

Mr.Mahesh Bhat
Lecturer, Mandsaur Institute of Pharmacy, Rewas-Dewda Road, Mandsaur-458001, M.P

Dr.D.N.Shrivastava
Prof.& HOD, Department of Pharmacology, B.R.Nahata College of Pharmacy, Post Box No.6, Mhow-Neemuch Road, Mandsaur-458001, M.P

Mr.Emmanuel Toppo
Lecturer, Mandsaur Institute of Pharmacy, Rewas-Dewda Road, Mandsaur-458001, M.P

Dr.Suresh Purohit
Principal, Mandsaur Institute of Pharmacy, Rewas-Dewda Road, Mandsaur-458001, M.P