Lecithin Microemulsion Based Systems for Dermal Delivery of Drugs: A
S. Khode, M. Lalan*
Department of Pharmaceutics, Babaria Institute of Pharmacy, Vadodara, Gujarat, India. ABSTRACT
The purpose of this review is to give an insight into the considerable potential of lecithin based
nanocarriers. The lecithin microemulsion and closely related microemulsion based systems are
currently of interest to pharmaceutical researchers. Conventional systems for topical delivery of drugs
meet many hindrances like reduced permeation and entrapment efficiency. Lecithin nanocarriers with
their enhanced bioavailability of drugs present a viable option to address the drawbacks of conventional
formulations. Soya and egg lecithin are widely being explored. However, the purity of lecithin plays a
significant role in gelation process. The review encompasses lecithin microemulsions, lecithin based
microemulsion gels, pluronic lecithin gels and lecithin stabilized microemulsion based hyrogels in
improving the topical delivery of drugs. Biocompatible lecithin based systems are known to furnish
ways of many promising discoveries in the field of safe and efficacious topical dosage forms.

Microemulsion, Organogel, Pluronic lecithin organogel, lecithin
1. Introduction
Drug delivery via skin is a preferred alternative to There has been extensive and concerted research overcome the drawbacks of traditional routes of in the area, focused on development of delivery administration. However, skin is a very formidable barrier to entry of both small and large permeation of drugs. Of the different explored molecules. Drug's physicochemical properties vistas, lipid based systems have created a niche like molecular weight less than 400 - 500 Da, for themselves. They are safe and effective drug partition coefficient in range of 1 to 3, non ionic delivery vehicles, give enhanced skin penetration nature, a balance between oil and water solubility, and accumulation at the targeted site and are melting point less than 200º C facilitates its clinically efficacious reducing side effects [3, 10]. passive diffusion through skin. Further it is desirable that the dose of drug is also Phospholipid based nanosized delivery vectors small [1,2]. This limits the number of drugs that have been exemplary in terms of their utility, can be used for topical delivery and requires a versatility and adaptability for topical drug vehicle that delivers the drug through the skin. delivery. These natural and biocompatible molecules associate to form nanosized assemblies *- Corresponding author in aqueous media which can be used as platforms Dr. Manisha Lalan, Associate Professor, Babaria for drug delivery [4]. Being amphiphillic in Institute of Pharmacy P.O. Varnama, Vadodara – nature phospholipids can deliver both polar and Mumbai NH # 8, Vadodara – 391240, Gujarat, non-polar drugs and act as bio-friendly permeation enhancers. Phospholipids' similarity Email: [email protected] to the biomembrane composition renders them J.PHARM.SCI.TECH.MGMT. Vol.1 Issue 1 2015 98 non-allergic. The most widely investigated The polar and nonpolar groups in lecithin permit phospholipid based systems are liposomes and solubilisation of both hydrophilic and lipophillic lecithin microemulsions [5]. drugs. Lecithin acts as penetration enhancer as it has high affinity to epidermal tissue owing to its Lecithin microemulsions as a delivery system, similarity to skin lipid components and also it come out to be more advantageous than increases hydration of stratum corneum [12, 13]. liposomes because of their ease of preparation, This leads to enhanced permeation of drugs due being economically viable alternative, high to alteration in skin lipid fluidization [14]. storage stability including avoidance of organic solvents and intensive sonication, easily scalable, minimal batch to batch variability. Further, their delivery of several drugs over the conventional topical preparations such as emulsions and gels. formation are added benefits [6]. At the same Mobility of drugs in microemulsions is more time, lecithin microemulsions are liquid in nature facile, as compared to the microemulsion with gel and thus have low contact time with the skin. former which will increase its viscosity and Transforming them into gel can improve its skin further decrease the permeation in the skin. The application and addresses its major drawback [7, superior transdermal flux from microemulsions 8]. This review delves into arena of lecithin has been shown to be mainly due to their high microemulsion and lecithin microemulsion based solubilization potential for lipophilic and gels in dermal delivery of drugs. hydrophilic drugs [15]. 2. Lecithin Based Microemulsion
Paolino et al conducted study on lecithin Microemulsions are thermodynamically stable, microemulsion of ketoprofen for skin penetration isotropic formulations having hydrophilic or and tolerability. The study showed that lipophillic nanodomains stabilized by the ketoprofen loaded microemulsions had enhanced presence of an amphiphillic surfactant at the permeation and good human skin tolerability as interface. The ultra low surface tensions observed compared to conventional formulations [16]. in microemulsions becomes a possibility by Lecithin microemulsion formulations increased addition of co-surfactants which increase the estradiol flux 200-700-fold over the control, but flexibility of the film and lower the interfacial permeability coefficients were decreased by 5-18 tension. Microemulsions have been explored for times. The superiortransdermal flux of estradiol dermal delivery of drugs extensively and well reviewed [9, 10]. It offers advantages like ease of insolubilization of estradiol by microemulsions preparation, thermodynamic stability, flexible interfaces promoting rapid drug diffusion [10]. Another significant investigation in lecithin Lecithin being amphiphillic in nature also microemulsions was on linker based systems by promotes microemulsion formation alone and in Yuan et al. Alcohol free microemulsion presence of other co-surfactants. The lecithin formulation was made possible with the molecule is composed of various phosphatides introduction of linker molecules. Linkers are such as phosphatidyl choline, phosphatidyl amphiphlic molecules such as sodium octanoate, decaglycerol monocaprylate/caprate and PEG-6- phosphatidyl inositol. Further, triglycerides and caprylic/capric glycerides, and lipophilic ones fatty acids are also a part of the composition. such as sorbitan monooleate. They segregate near They are mainly obtained from soyabean and egg the oil–water interface but only from one side of the interface [10, 17]. It has been observed that lecithin linker-based microemulsions have an excellent solubilization capacity for a broad J.PHARM.SCI.TECH.MGMT. Vol.1 Issue 1 2015 99 category of oils and increases dermal drug comprise of phospholipids (lecithin), appropriate penetration [18, 19]. Lecithin is the major organic solvent, and a polar solvent. During the surfactant used in the system and remains investigation of the suitable conditions for soy unaffected by the formulation conditions like lecithin to form reverse micelles, gel like temperature and electrolyte concentration [20]. structure was observed by Scartazzini and Luisi The higher flux of the active from the system to in 1988 [24]. They observed a sudden increase in the skin obtained with linker microemulsions is the viscosity by the addition of minimal amounts produced by combination of linkers that increase of water into organic solutions of soy lecithin the mass transfer and reduce the interfacial [24]. Since then a lot of research has been done tension of system. Also this can be attributed to the formation of smaller aggregates (6-10nm) by LMBGs consist of a 3-dimensional network of using hydrophilic linker that can penetrate entangled reverse cylindrical (polymer-like) through the epithelial tissue with ease [20,21]. micelles (Figure 1), which immobilizes the
Moreover, the combination of hydrophilic and macroscopic external organic phase to a gel like lipophilic linkers offers better solubilisation state [25, 26]. The supramolecularly associated capacity [22, 23]. The linker based systems are micellar aggregates in the entangled state less toxic than the alcohol-based lecithin resemble to that of uncrossed polymers microemulsion systems. This is because of the fact that the hydrophilic linkers concentrates on [28,29].These gels-like systems were called fluidizing the oil/water interface and probably the microemulsion-based gel or organogel; owing to interstitial spaces between cells whereas medium the presence of organic solvents [10]. The basic chain alcohols fluidizes the membranes of living three Components in an LMBG are a polar cells, inducing cell lysis [20, 21]. Linker based phase, a non-polar phase and a surfactant or lecithin microemulsions can also be employed for extended release systems. The microemulsion interfacial activities as well as acts as gelating imbibed in the skin works as a drug reservoir and agent also. The naturally occurring unsaturated was shown to provide extended release for over lecithin with high degree of purity containing 24 h. The drug uptake in the skin increases with atleast 95% phosphatidyl content have the increase in the drug loading of microemulsion, ability to form gel like structure. The synthetic, dosage of microemulsion and the application hydrogenated and poorly purified lecithin are time. It can be formulated for numerous drugs, is devoid of gel forming property [24, 29, 30, 31]. economic and customizable [21]. A wide array of organic solvents have been used or can be explored for the preparation of The most obvious drawback of microemulsion lecithin microemulsion gels, of which fatty acid systems is its fluidity or low viscosity which esters (eg., isopropyl myristate, isopropyl limits its contact time with the physiological palmitate) are of particular interest for membrane. There have been various approaches at increasing the viscosity of lecithin based formulations so developed exhibit enhanced systems like its transformation to an organogel or biocompatibility using a hydrogel base to increase the viscosity. biodegradability [32, 33]. Aqueous media The further sections delve into viscosity enhanced constitutes the polar phase in most of the cases. lecithin systems for dermal delivery of drugs. The addition of cosolvents like glycerol, ethylene glycol and formamide in non-aqueous 3. Lecithin Microemulsion Based Gel or
media can also aid to transform a non-viscous Organogel
lecithin solution into a gel. It is required that the Lecithin microemulsion based gels (LMBGs) are gel forming solvent should be endowed with thermodynamically stable, clear, viscoelastic, properties like high surface tension, dielectric biocompatible, and nonbirefringent gels. They constant, polarity index and a strong ability to J.PHARM.SCI.TECH.MGMT. Vol.1 Issue 1 2015 100 form hydrogen bonding [27, 34]. Recently bile enzymes. They are suitable matrix for salts have been used in the formation of long transdermal as well as topical formulations and flexible reverse micellar chains of LMBG that are non-irritating. Some of remarkable features can resemble to the role of water in of lecithin organogels are thermoreversible organogelling [35].The lecithin microemulsion nature, insensitivity to moisture, resistant to gels are fascinating as delivery vectors for their microbial contamination and spontaneous ability to solubilise lipophilic, hydrophilic, and formation [31, 32, 36]. Lecithin

Figure-1 Cylindrical/micellar structure of lecithin in organogel

3.1 Mechanism of skin permeation of
4. Pluronic lecithin microemulsion gel
microemulsion based gels
Pluronic Lecithin Organogels (PLO) have gained Skin is a multilayered barrier comprising three importance in recent years as transdermal drug main layers viz. epidermis, dermis and delivery systems as the high purity grade of hypodermis. Compromising the barrier is lecithin is expensive and difficult to obtain in required at times to facilitate drug diffusion. large quantities [10, 52]. Therefore, some Organogels penetrate through the skin easily researchers tried to incorporate synthetic due the presence of non-polar solvents which acts as penetration enhancers. On addition of microemulsion gels, for their feasibility as polar solvents gel formation takes place, as a result area of lecithin polar region increases. satisfactory organogel could be obtained with This additionally increases the thermodynamic relatively lesser purity of lecithin [53, 54]. activity of the drug driving it into skin. The Pluronics are block copolymers of ethylene oxide general mechanism of skin permeation through and propylene oxide and are non-ionic, non- organogels includes formation of thin film on irritating and are absorbed quickly and also the skin surface, drug diffusion through the known commonly as poloxamers. [10, 61]. They carrier system, followed be partitioning of drug are liquid at refrigerated conditions (4oC) and through the epidermal layer and then form a thermoreversible gel at body temperature penetrating to the deeper dermal layers. This or they can be termed as in-situ gels [56]. The results in preferential accumulation in different concept of PLO gel was first reported in the layers of skin. Numerous researchers have 1990s by Jones and Kloesel [52]. worked on lecithin organogels for topical drug
delivery (Table1 and 2) [37].
J.PHARM.SCI.TECH.MGMT. Vol.1 Issue 1 2015 101
Table-1 Topical delivery of various substances using lecithin organogels

Drug class
Name of drugs/agents
Diclofenac, ibuprofen, indomethacin, ketoprofen, piroxicam, aceclofenac [29-39] Anti-hypertensive Aromatic tetra-amidines[40] Fluoxetine, paroxetine, amitriptyline, trazadone[41] corticosteroids[40] Anti-cholinergic Scopolamine [39] agonist
Vitamin A and C[38] Proteins and peptides[39], botulinium toxins[40]
Table-2 Organogel formulations and their findings investigated

Organogel Formulation
Broxaterol and Scopolamine in lecithin-IPP Potential for transdermal delivery of drugs based gel Phosphatidylcholine (PC)-IPP based gel Examined for transdermal transport of amino acids, peptides and various drugs [43] Soybean lecithin/IPP gels composed of 10% Transdermal delivery of aromatic tetra-
to 20% of esters like ethyl acetate or propyl amidines to assess anticancer activity [44]
Diclofenac and indomethacin in lecithin-IPP Imoroved efficacy though dermal delivery
Phytosphingosine organogel Explored for treatment of scars [47] composed of Soyabean Phosphatidylcholine,
IPP, ethanol, and water.
Ketamine hydrochloride and Amitryptiline Enhanced skin penetration Hydrochloride incorporated in Soy lecithin- Significant partitioning of the drugs into isopropyl myristate (IPM) organogel the skin layers [48] containing Increased skin permeation [49] Nicardipine
Lecithin Organogel of Methimazole
Significant percutaneous absorption [50] Digoxin in lecithin organogel Topical efficacy for the treatment of muscle spasm [45] Cyclobenzaprin incorporated in lecithin Useful for bruxism [46]
Lecithin Organogel containing Propranolol Increase in concentration of lecithin
resulted in lower flux of drug [51] J.PHARM.SCI.TECH.MGMT. Vol.1 Issue 1 2015 102 PLO's are biphasic systems comprising an oil in PLOs, drug can be incorporated in either oil phase (e.g. isopropyl myristate or isopropyl phase or aqueous phase (Table 3&4) [57, 58].
palmitate) and an aqueous phase having 5. Lecithin stabilised microemulsion gels
Pluronic F127 [55]. Water solubilises the Lecithin based microemulsions can be pluronics and hydrophilic drugs and thus act as incorporated into gel matrices. Hydrogels of structure forming agent and stabilizes gel these microemulsions were formulated by addition of hydrophilic polymers such as spontaneously and thus have prolonged shelf gelatin, carrageenan, and carbopol to enhance life. Gel formation can be enhanced by addition the viscosity of the system (Table 5). Here the
of agents other than water such as propylene internal microemulsion droplets are not glycol, propyl gallate and hydroxypropyl disturbed and continue to be in fluid state with cellulose. Depending on the solubility of drug, the external water phase being gelled [8, 15, 82-84] Table-3 Topical delivery of various substances using Pluronic lecithin organogels
Drug class
Name of the drugs
Non-Steroidal anti-inflammatory Piroxicam [59], diclofenac [60], Ketoprofen [63] drugs (NSAIDS) Dexamethasone[61] progesterone[84], testosterone[85], tamoxifen[86] Promethazine [62], Ondansetron [63], scopolamine [64], metoclopramide [65] Methadone, morphine, buprenorphine [66] Benzocaine, Lidocaine [67] Antipsychotic drugs Haloperidol, prochlorperazine [68] Calcium channel blockers Miscellaneous drugs Methimazole [50], ketamine hydrochloride [65], selegiline hydrochloride [67], fluoxetine [66], clonidine [67], carbamazepine [67], baclofen [67], insulin J.PHARM.SCI.TECH.MGMT. Vol.1 Issue 1 2015 103
Table-4 Pluronic lecithin organogel formulations and their findings

PLO gel formulation
of Less pain, Fewer side effects [69] Ketoprofen Diclofenac, Ibuprofen, Ketamine in PLO Reduced pain and increased functionality, potential for gel effective treatment for Osteoarthritis [70] Ondansetron in PLO inflammatory effects in response to intradermally injected capsaicin in humans[63] or Efficacious in eczema or psoriasis by increasing skin isopropyl myristate containing pluronic hydration[71] and water PLO of Cyclobenzaprin NSAIDs incorporated in PLO Rapid onset of action, Less side effects [67] PLO gel containing extract of Arnica Used in pain management [73] Montana Reduces neuropathic, sympathetic, and myofacial pain by improving ketamine penetration[74] PLO gel of saw palmetto extract For the treatment of androgenic alopecia[75] PLO gel of Bromelain and capsaicin Excellent for topical delivery of large molecule [76] PLO gel of hormones (eg, progesterone) Effective transdermal delivery of hormone [77] Testosterone (Micronized form) in PLO Achieves effective systemic levels of hormone [78] gel Fluoxetine hydrochloride incorporated in Useful for systemic delivery of the compound in feline PLO gel Tamoxifen PLO gel Stable, ease of application and biocompatible[80] Lornoxicam PLO gel Improved transdermal permeation[81] Table5 Lecithin stabilized microemulsion formulations and their findings

Lecithin stabilized microemulsion of Enhanced skin penetration and drug release[87]
ketorolac tromethamine
Microemulsion based hydrogel of Non-irritating, anti-inflammatory Microemulsion based hydrogel of Enhanced skin permeability
lidocaine and prilocaine
Skin compliance
Safe and efficacious[85]
J.PHARM.SCI.TECH.MGMT. Vol.1 Issue 1 2015 104 6. Conclusion
With the ever-increasing promotion of green parameters in drug selection and loading for ingredients in every aspect of science and transdermal drug delivery, Indian J. Pharm. technology, drug delivery too does not lag Sci. 70, (2008), pp. 94. behind. The review tries to summarize and [3] M.B.R. Pierre, I.d.S.M. Costa, Liposomal bring together an update on state of art and systems as drug delivery vehicles for dermal applications of lecithin based microemulsions in dermal delivery of drugs. Lecithin based Dermatol. Res. 303, (2011), pp.607–621. delivery systems by virtue of their similarity to [4] L. Zarif, Elongated supramolecular biomembranes are nontoxic in nature as well as assemblies in drug delivery, J. Control. are efficient modulators of drug permeation. Release 81, (2002), pp.7–23. The lecithin being amphiphillic in nature aligns [5] M. Changez, J. Chander, A.K. Dinda, itself along the interface between polar and nonpolar phase. Its structure endows it with a hydrochloride by lecithin microemulsion: in capacity to form lamellar structures and forms vivo, Colloids Surf. B: Biointerfaces 48, reverse micelles in non polar external phase. (2006), pp.58–66. The introduction of polar media induces growth [6] D. Paolino, C.A. Ventura, S. Nistico, G. in the micelles to form long tubular structures Puglisi M. Fresta, Lecithin microemulsions which helps in immobilizing the external for the topical administration of ketoprofen: media. They have shown potential in percutaneous adsorption through human skin augmenting dermal deposition of drug which is and in vivo human skin tolerability, Int. J. attributed to its similarity to physiological Pharm. 244, (2002), pp.21–31. biomembrane and allows it to blend with the [7] W. Tian, S. Schulze, M. Brandl, G. Winter, lipid mantle of the membrane. However, the Vesicular phospholipid gel-based depot nature of polar phase, non polar phase and formulations for pharmaceutical proteins: physicochemical properties of the drug development and in vitro evaluation, J. molecule influences its loading in the system. Control. Release 142, (2010), pp.319–325. Although they are excellent delivery vectors, [8] X.-Y. Xuan, Y.-L. Cheng, E. Acosta, their natural origin warrants strict quality Lecithin-linker microemulsion gelatin gels for extended drug delivery, Pharmaceutics 4, endeavouring strategies to formulate stable and (2012), pp.104–129. consistent delivery systems not affected by [9] A. Teichmann, S. Heuschkel, U. Jacobi, W. variations in lecithin origin and quality. Biggest Sterry, Comparison of stratum corneum challenge is to commercialize an increasing penetration and localization of a lipophilic number of these promising concepts. The trend model drug applied in an o/w microemulsion has picked up with a few products reaching the and an amphiphilic cream, Eur J. Pharm. and clinics and it is expected to scale the numbers Biopharm. 67, (2007), pp.699–706. [10]Y.S.R. Elnaggar, W. Refaie, M. Massik, DECLARATION
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