EMULGEL-NOVEL TOPICAL DRUG DELIVERY SYSTEM–A COMPREHENSIVE REVIEW
HTML Full TextEMULGEL-NOVEL TOPICAL DRUG DELIVERY SYSTEM–A COMPREHENSIVE REVIEW
Davinder Kumar, Jasbir Singh, Mamta Antil and Virender Kumar *
College of Pharmacy, Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, University of Health Sciences, Rohtak - 124001, Haryana, India.
ABSTRACT: Emulgel systems are currently of attention to the pharmaceutical scientists because of their substantial potential to act as drug delivery vehicle by incorporating a broad range of drug molecules. These are either emulsion of water in oil type or oil in water, which is gelled by mixing it with a gelling agent. Incorporation of emulsion into gel makes it a dual control release system & also increases its stability. Due to lack of insoluble excipients and excess oily bases, it demonstrates better drug release as compared to other topical drug delivery system. Due to nongreasy because of the presence of gel phase which favors good patient compliance. In order to understand the potential of emulgel as delivery vehicles, this review gives an overview of the ideal properties, formation, and characterization of emulgels. The use of emulgel -based systems as drug delivery vehicles is reviewed, with particular emphasis being placed on recent developments and future directions.
Keywords: Emulgel, Gelling agent, Emulsion, Topical agents |
INTRODUCTION: The human being, since many ages get experienced with various types of diseases influencing their health and prosperity. The effort to cure diseases has been driving in the discovery of various medications, drug and delivery systems. To get a remedial response of drug required for treatment of illness different routes of administration are taken after. Route of administration depends on sort and seriousness of the disease. For skin disorders, the topical route is generally favored. Topical drug delivery systems are such system in which direct application of a formulation containing an active pharmaceutical ingredient to the skin to obtain the localizing effect of drug. 1
Topical drug delivery system has several advantages such as the ability to deliver drug more selectively to a specific site and prevention of incompatibility associated with gastro-intestinal. 2 Moreover, topical deliveries by avoiding first pass metabolism provide an increased bioavailability and consistent delivery for an extended period. 3, 4 In topical drug delivery system, drug reaches to the site of action via diffuses out of the delivery system and their absorption takes the place of the skin. 5 Percutaneous absorption can be improved by increasing the release rate of the drug from dosage form. 6 The release rates of medications from topical preparations depend straightforwardly on various physical, chemical properties of the carrier and the medication utilized. 7, 8
Since the mid-1980s, emulsion gels have been picking up significance in pharmaceutical topical semisolid dosage forms. Their wide usage as pharmaceutical dosage form originates from the wide use of emulsion systems, especially for dermatological formulae.
Emulgel are emulsions, either of the water-in-oil or oil-in-water type, which are gelled by mixing with a gelling agent. 9 The emulsion also acts as controlled release drug delivery system in which drug particles entrapped in internal phase go through the external phase to the skin and slowly get absorbed. The drug reaches the external phase of the skin in a controlled manner through the internal phases which act as a reservoir of the drug. Gel captures small drug particles and provides its release in a controlled manner because of a cross-linked network. It prolongs the contact period of medication over the skin because of its mucoadhesive property. 10 Since Emulgel possesses the property of both gel and emulsions it acts as dual control release system. 11 Water-in-oil emulsions are employed more extensively for emollient actions and for the treatment of dry skin and emollient applications while oil-in-water emulsions are most useful in general cosmetic acts as a water washable drug bases. 12- 14
When emulsion posses the property of thixotropic then the processes of penetration into the skin are simplified. Hence to improve emulsion penetration and stability it is incorporated into the gel. Further, gels for dermatological use have a few positive properties, for example, being emollient 15, 16, greaseless, thixotropic, easily removable, nonstaining and compatible with various excipients. Release rate, as well as the stability of incorporated drug, can be affected by type and concentration of polymer which form the gel. Emulgels have good patient acceptability. It can be suitably applied to the skin due to its non-greasy nature in comparison to other topical formulations such as ointments, creams etc. which are very much thick and require excess rubbing. 17-20 Emulgels may serve as a better option when one is concerned with the topical delivery of poorly water soluble drug. It has also proven better and a stable vehicle for poorly water -soluble or hydrophobic drugs. 21-23
TABLE 1: IDEAL PROPERTIES OF DRUG CANDIDATE TO FORMULATE AS EMULGEL 24
S. No. | Drug Candidate |
1 | Drug dose should be low i.e. less than 10 mg |
2 | Molecular weight of drug should be 400 Dalton or less |
3 | Half life of drug 10 hr or less |
4 | Partition coefficient i.e. Log p ( Octanol-water) between 0.4-0.8 |
5 | Having a skin –permeability coefficient more than |
6 | Oral bioavailability and therapeutic index should be low. |
7 | Drug should be non irritating and non-sensitizer having a less polarity |
Various ingredients of Emulgel formulation:
2.1 Aqueous material: This forms aqueous phase of the emulsion. Generally, water is used.
2.2 Oils: They are responsible for the oily phase of the emulsion. The oil phase has great importance in the formulation of emulsion /microemulsion/ nanoemulsion as physicochemical properties of oil (e.g., molecular volume, polarity, and viscosity) significantly govern the spontaneity of the emulsification /micro- emulsification / nano emulsification process, the droplet size of the respective emulsion, drug solubility. Usually, the oil, which has the maximum solubilizing potential for the selected drug candidate, is preferred as an oily phase for the formulation of emulsion/ microemulsion/nanoemulsion. This helps to attain the maximal drug loading. Hence, the choice of the oily phase is often a compromise between its tendency to solubilize the drug and its capability to
facilitate the formation of the respective emulsion with desired characteristics. Oil phases which are used in development of emulgel are balsam oil, 25 birch oil, 26 castor oil, 27-29 isopropyl myristate, 30-32 myrrh oil, 33 rose hip oil, 34-35 wheat germ oil. 36-38
2.3 Emulsifiers: Emulsifiers are used to control emulsification process and stability. By incorporating an appropriate emulsifying agent stability of emulsion can be increased because these are thermodynamically unstable. Surfactants having HLB values greater than 8 such as the nonionic surfactant (spans, tweens) are used in the formulation of o/w emulsions whereas mineral oils such as liquid paraffin have HLB value less than 8 and therefore are used in the formulation of water in oil emulsions. In comparison to the individual system of span or tween, mixtures of span 20 and tween 20 results greater stability of the emulsion. 39
2.4 Permeation enhancer: Penetration enhancers are the substances that assist the absorption of penetrant through the skin by temporarily thinning the impermeability of the skin. Ideally, these materials should be pharmacologically inert, nonirritating, nontoxic, and compatible with the excipients and drugs, colorless, odorless, tasteless, and inexpensive and have good solvent properties.
The enhancer should not guide to the loss of body fluids, electrolytes, and other endogenous materials, and skin on its removal should immediately regain its barrier properties. Various penetration enhancers used in the emulgel formulation are oleic acid, 40 clove oil 41 and menthol 42 etc.
2.5 Gelling Agents: Gelling agents are used to forming gel base which by incorporating emulsion to form emulgel. These are also known as thickening agents which expand the consistency of any dosage form by swelling in the aqueous phase and forming gelly like structure. 43 Incorporation of gelling agent to a system makes it thixotropic. 44
HPMC based Emulgel was found to be superior to Carbopol based Emulgel since it showed better drug release rate. NaCMC based Emulgels for vaginal application since it showed higher mucoadhesivity which increased drug residence time and also best in-vitro and in-vivo performance. HEC based Emulgel showed low mucoadhesion but good drug release profiles and rheological characteristics. Pemulen based Emulgel meant for buccal administration.
TABLE 2: VARIOUS GELLING AGENTS USED IN PHARMACEUTICAL DOSAGE FORMS
S.no | Gelling agents | Concentration used (%w/w) | Pharmaceutical adaptability | Active pharmaceutical ingredient | References |
1 | Sodium CMC | 3-4% | stand autoclaving hence suitable for sterile gels | Benzydamine | 45 |
2 | Carbopol-934 | 1% | Provide controlled release of API incorporated | Chlorphenesin | 46 |
3 | Carbopol-940 | 1% | Because of high viscous gel, provide controlled release of API incorporated | Mefenamic acid | 47 |
4 | HPMC | 2.5% | Having good stability, microbial resistance, | Clorphenesin | 48 |
5 | Combination of HPMC & Carbopol | 1.2% | Combination improve stability | Ketorolac, clotrimazole | 49-50 |
6 | Pluronic® F127 | 1-3% | Good clarity and better solubility in cold water | Piroxicam | 51 |
7 | Pemulen | 0.1-0.4% | Provide rapid release of oil phase, excellent stability | Flurbiprofen | 52 |
- Formulation of emulgel: 53-54
Step1: Preparation of gel using the gelling agent: Sufficient quantity of Carbopol 940 (1% w/w) was weighed and sprinkled onto warm distilled water with continuous stirring. The dispersion was allowed to hydrate for 1-2 hours. Other ingredients like propylene glycol (10 % w/w) and glycerol (10 % w/w) were added subsequently to the aqueous dispersion with continuous stirring. A required quantity of drug (1 % w/w) was added and properly dispersed. The dispersion was neutralized to pH 6 using triethanolamine and the final weight was adjusted with distilled water. The gel was sonicated for 15 minutes and kept overnight to remove air bubbles.
Step 2: Preparation of Emulsion: Depending upon whether oil in water or water in oil emulsion was formulated.
Step 3: Incorporation of the emulsion into gel base: Finally emulsion was incorporated in gel base to form emulgel.
- Characterization of Emulgel:
4.1 Physical appearance: The prepared emulgel is inspected for the colour, homogeneity, consistency. 55
4.2 pH: The pH values of 1% aqueous solutions of the prepared gels were measured by a digital pH meter. Electrodes were completely dipped into the semisolid formulations and pH was noted. 56
4.3 Spreadability: To study the spreadability of formulations, special apparatus was designed. Spreadability is expressed in terms of time in seconds taken by two slides to slip off from formulations, placed between, under the application of a certain load lesser the time is taken for the separation of the two slides, better spreadability. Two glass slides of 6x2 cm each were selected. The formulation was placed over one of the slides whose spreadability had to be determined (500mg). This slide was placed over the other slide in such a way such that formulation was sandwiched between the two slides. The formulation between the two slides was squeezed consistently to frame a slight layer, for this reason, weight (100 gm) was set upon the upper slide. The excess of the formulation adhering to the slides was scrapped off after the weight was removed. The lower slide was fixed on the surface of the apparatus and the upper slide was tied to a string. To this sting load (20 gm) could be applied with the help of a simple pulley. Under the direction of weight applied the time taken for the upper slide to move the distance i.e of 6cm and separate away from the other slide(lower) was noted. The experiment was repeated (n=3) and the average of such determinations was calculated for each formulation
Where, M= Weight which is tied to the upper slide (20gm)
L= Length taken of glass slide (6cm)
T= Time taken (seconds)
The delivery of the correct dose of the drug depends highly on the spreadability of the formulation. 57
4.4 Swelling Index: For determination of swelling index of formulated emulgel following procedure adopted, 1 gm of the gel is taken on porous aluminum foil and then placed separately in a beaker of 50 ml containing 10 ml 0.1 N NaOH. Then samples were taken from beakers at different time points and put it on a dry place for some time after it reweighed. Swelling index is calculated as follows:
Where,
Wo = Initial weight of emulgel at zero time
Wt = Weight of swollen emulgel after time t
(SW) % = Percent swelling Index 58
4.5 Extrudability study of topical emulgel (Tube Test): It is a typical experimental test to measure the force required to expel the material from the tube. The formulation, whose extrudability checked, filled in clean, lacquered aluminum collapsible metal tubes. The tubes were pressed by the help of finger to extrude the material. In the present study, the method adopted for evaluating emulgel formulation for extrudability is based upon the quantity in the percentage of emulgel. Emulgel extruded from lacquered aluminum collapsible tube on the application of weight in grams required to extrude at least 0.5 cm ribbon of emulgel in 10 seconds. 59 The experiment was repeated (n=3) and the average of such determinations was calculated for each formulation:
4.6 Bio-adhesive strength measurement: A modified balance method was using for bioadhesion measurement. The two pans were removed from physical balance. On the left side, a glass slide was hanged and a 100 ml beaker was used in place of right side pan. A weight of 20 g was hanged on the left side, for balancing the assembly. Another glass slide was placed below the hanged slide. On both slides, portions of hairless fresh rat skin were attached. One gram of gel was placed between two rat skin faces. To form bioadhesion bond, a little pressure was applied, and then slowly water was added to right side beaker, till the gel was separated from one face of rat skin attached. The volume of water added was converted to mass. This gave the bioadhesive strength of gel in grams. 60
4.7 Drug Content Determination: Gel formulation (1 gram) was dissolved in suitable solvent. Filtered it to obtain clear solution. The resulting solution absorbance was noted using UV Visible spectrophotometer. Drug content was determined from calibration curve for drug. 61
4.8 In-vitro drug release studies In-vitro release behaviour of the drug from emulgel formulations were investigated using egg shell membrane. An interesting investigation used egg membrane which, like human stratum corneum, consists mainly of keratin.62 By using 0.5M hydrochloric outer shell of the whole egg was dissolved which resulting in a membrane. Thereafter, the contents of the egg may be detached and the membrane washed and refrigerated or soaked in isopropyl myristate under vacuum to impregnate the keratin matrix. The replacement of water in the membrane with this lipid is assumed to increase its likeness to stratum corneum biochemistry. The Keshary-chien cell was used for release and permeation study. One gram of gel was applied on 9.8 cm2 area of the surface of egg membrane tied to the lower end of donor compartment. The volume of the receptor fluid was reserved 37.5 ml.
The temperature condition of the receptor fluid maintained at 37˚ C and stirred continuously at 100 rpm on a magnetic stirrer. Aliquots of 3.0 ml were withdrawn and analyzed for the drug content after suitable dilutions by spectrophotometric method. The volume of fluid which was withdrawn for analysis be replaced with the same volume of the fresh buffer after each sampling. The cumulative amount released across the egg membrane was calculated and plotted against time. The best batches showing high percent release were selected further for ex-vivo studies using rat skin.
4.9 Ex-vivo skin permeation and retention studies: Albino rat 10-12 weeks old weighing 200-250 g was used. The excised skin was placed in aluminum foil the dermal side of the skin was delicately teased off for any following fat and/or subcutaneous tissue. The skin was then precisely checked through an magnifying glass to guarantee that specimens were free from any surface inconsistencies, for example, small openings or cervices in the part that was utilized for transdermal permeation studies. The skin was washed with physiological buffer saline and freshly obtained skin was used in all experiments.
The ex-vivo skin permeation of drug from different formulations was studied using Keshary-chien cell. The effective permeation area of the diffusion cell was 9.8 cm2. The receptor compartment has a volume of 37.5 ml. Albino rat skin was sandwiched securely between donor and receptor compartment with the donor compartment having epidermis site. The donor compartment was maintained at 37±1oC with constant stirring . The emulgel formulation was applied to the epidermal surface of the rat skin. At predetermined time interval for 24 hr (0.5hr, 1hr, 2hr, 4hr, 6hr, 8hr, and 24hr), 3.0 ml of aliquots were withdrawn and were replaced with an equal volume of fresh receptor compartment solvent to ensure sink condition. The cumulative percentage drug diffused across the skin was calculated at each sampling point.
The amount of free drug content in the receptor compartment and the amount of drug remained on the epidermal surface of the skin on subtraction from the initial drug content of the formulation applied resulted the amount of drug content in the skin. The ex-vivo permeation study of emulgel is compared with the marketed emulgel for permeation characteristics. All the determinations were carried out in triplicate and the data were compared by ANOVA.
4.10 Stability Studies: The optimized emulgel formulation was selected for stability study. Sufficient quantity of emulgel formulation was sealed in 10 gm collapsible tube in triplicate, and subjected to stability studies at 5°C, 25°C,/60%RH, 30°C 65%RH and 40°C/ 75%RH for a period of 3 months. The samples were analyzed at predetermined time intervals for pH, physical appearance, rheological properties and drug content.63
4.11 Kinetics Modeling: Data obtained from ex-vivo permeation studies were fitted into zero order, first order, Higuchi, and mathematical models for evaluation of drug release kinetics. The model for best fit was predicted from the value of R2. For an ideal fit, value of R2 i.e. higher, the value of R2 best was the model fitted. Hence, the model which gives the R2 value nearest to 1 describes the best order of drug release. 64
TABLE: 3 CURRENT ELEVATIONS IN DEVELOPMENT OF EMULGEL FOR VARIOUS DRUGS
Drug | Aim | Use | References |
Amphotericin B | Evaluation of the in vivo leishmanicidal activity of amphotericin B emulgel: An alternative for the treatment of skin leishmaniasis | Leishmaniasis therapy | 65 |
Metronidazole
and ciprofloxacin
|
Groundnut oil based emulsion gels for passive and iontophoretic delivery of therapeutics | Passive and iontophoretic delivery of therapeutics | 66 |
Amlodipine besylate | Preparation of amlodipine besylate emulgels for transdermal administration and its percutaneous permeability in vitro | Transdermal delivery | 67 |
Acyclovir and ketoconazole | Topical delivery of acyclovir and ketoconazole | Viral and fungal cutaneous manifestations | 68 |
Lacidipine | Novel non-ionic surfactant proniosomes for transdermal delivery of lacidipine: optimization using 23 factorial design and in vivo evaluation in rabbits | Antihypertensive | 69 |
Pravastatin | Optimised transdermal delivery of pravastatin | 70 | |
Ciprofloxacin | Genipin-Crosslinked Gelatin-Based Emulgels: an Insight into the Thermal, Mechanical, and Electrical Studies | 71 | |
Diclofenac sodium | Evaluation of skin penetration of diclofenac from a novel topical non aqueous solution: A comparative bioavailability study | Pain relief | 72 |
Diclofenac sodium | Nanoemulsion-based gel formulation of diclofenac diethylamine: design, optimization, rheological behavior and in vitro diffusion studies | Management of pain | 73 |
Pinhão starch | Pinhão starch and coat extract as new natural cosmetic ingredients: Topical formulation stability and sensory analysis | Antioxidant activity | 74 |
Terpinen-4-ol | The effect of rheological behavior and microstructure of the emulgels on the release and permeation profiles of Terpinen-4-ol | Antimicrobial properties | 75 |
Betamethasone dipropionate | Development of a topical ointment of betamethasone dipropionate loaded nanostructured lipid carrier | For the treatment of atopic dermatitis | 76 |
LEVORAG® Emulgel
: Hibiscus esculentus extract, Carboxymethyl beta-glucan Dimethicone, glycerine, prunus amygdalus dulcis oil, borago officinalis seed oil Malva sylvestris extract, calendula officinalis extract, glycyrrhiza glabra extract |
Prospective multicenter observational trial on the safety and efficacy of LEVORAG® Emulgel in the treatment of acute and chronic anal fissure | For treatment of acute and chronic anal fissure | 77 |
Cyclosporin A | Formulation and evaluation of Cyclosporin A emulgel for ocular delivery | Topical ocular delivery | 78 |
Meloxicam | Formulation and characterisation of Meloxicam loaded emulgel for topical application | Anti-inflammatory | 79 |
Nimorazole | Preparation and evaluation of Radiosensitizing agent Nimorazole in topical emulgel | hypoxic cell radiosensitizing agent | 80 |
Ketoprofen | Formulation development, in vitro and in vivo evaluation of microemulsion-based gel loaded with ketoprofen | Anti-inflammatory | 81 |
Calcipotriol | Calcipotriol delivery into the skin as emulgel for effective permeation | In treatment of Psoriasis. | 82 |
Allopurinol | Design and development of allopurinol emulgel | 83 | |
Terbinafine hydrochloride | Formulation, development and in-vitro evaluation of Terbinafine hydrochloride emulgel for topical fungal infection | In treatment of fungal infection | 84
|
Silver sulfadiazine | Development and characterization of silver sulfadiazine emulgel for topical drug delivery | Antimicrobial activity | 85 |
Piroxicam | Effects of various penetration enhancers on percutaneous absorption of piroxicam from emulgels | Anti-inflammatory | 86 |
Ketorolac Tromethamine | The enhancement of transdermal permeability of water soluble drug by niosome-emulgel combination | Anti-inflammatory | 87 |
- Various marketed Emulgel formulation: Emulgel are commercially available in markets; some preparations of which are listed as following in Table. Voltaren Emulgel is a topical analgesic gel that provides relief in shoulder pain, back pain and reduces swelling. Voltaren Emulgel is non-greasy, white pleasant-smelling gel which is available in a 100g tube having a active ingredient diclofenac sodium 1% w/w (as diclofenac
diethylamine). Another emulgel is Diclomax Emulgel which is used in treatment inflammation of the tendons, ligaments, muscles and joint and manufactured by Torrent Pharma. Miconaz H emulgel which is manufactured by medical union pharmaceuticals having active ingredient miconazole nitrate and hydrocortisone posses bactericidal, fungicidal, anti-inflammatory and antipruriginous properties.
TABLE 4: VARIOUS MARKETED EMULGEL FORMULATIONS
Marketed formulation | API | Manufacturer | Use |
Voltarol 1.16% emulgel | Diclofenac sodium | Novartis | Antiinflamatory |
DiclomaxEmulgel | Diclofenac sodium | Torentpharma | Antiinflamatory |
Miconaz-H-emulgel | Miconazole nitrate,
Hydrocortisone |
Medical union
Pharmaceuticals |
Topical
corticosteroid and antifungal |
- Future prospective: During formulation & development of any new formulation the most common problems faced from hydrophobic behavior of drugs which leads to poor water solubility and bioavailability problems. Because of hydrophobic nature of many drugs delivery of these to the biological system have be challenging. Creams, ointments and lotion are of different types of drug delivery system which has been applied topically have excellent emollient properties but retards the release of drugs due to presence of oleaginous bases. As compared to other topical systems gel provides quicker release of drug because gel provides aqueous environment to drugs. Hydrophobic drug can be incorporated in oily base and delivered to skin by using emulgel. All such points of interest of Emulgel over other topical drug delivery systems make them more effective and profitable. In future these properties will be utilized to convey more number of topical medications as Emulgel.
REFERENCES:
- Zignani M, Tabatabay C, Gurny R: Topical semi-solid drug delivery: kinetics and tolerance of ophthalmic hydrogels. Adv. Drug Deliv. Rev. 1995; 16: 51–60.
- Kikwai L, Babu RJ, Prado R, Kolot A, Armstrong CA, Ansel JC, Singh M: In vitro and in vivo evaluation of topical formulations of spantide II. AAPS PharmSciTech 2005; 6: E565–E572.
- Moshfeghi AA, Peyman GA: Micro- and nanoparticulates. Adv. Drug Deliv. Rev.2005; 57: 2047–2052.
- Rosen H, Abribat T: The rise and rise of drug delivery. Nat. Rev. Drug Discov2005; 4: 381–385.
- Zi P , Yang X, Kuang H, Yang Y, Yu L: Effect of HPbeta CD on solubility and transdermal delivery of capsaicin through rat skin. Int. J. Pharm. 2008; 358: 151–158.
- Shokri J, Azarmi S, Fasihi Z: Effect of various penetration enhancers on percutaneous absorption of piroxicam from emulgel. Res. Pharm. Sci.2012; 7: 225–2234.
- Foldvari M: Non-invasive administration of drugs through the skin: challenges in delivery system design. Pharm. Sci. Technol. Today2000; 3: 417–425.
- Elsayed MM, Abdallah OY, Naggar VF, Khalafallah NM: Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int. J. Pharm.2007; 332: 1–16.
- Mohamed MI: Optimization of chlorphenesin emulgel formulation. AAPS J.2004; 6: 26.
- Alexander A, Ajazuddin, Tripathi DK, Vrema ST, Maurya J, Patel S: Mechanism responsible for mucoadhesion of mucoadhesive drug delivery system: a review. Int. J. Appl. Biol. Pharm. Technol.2011; 2: 434–445.
- Jain A, Deveda P, Vyas N, Chauhan J: Development of antifungal emulsion based gel for topical fungal infection. IJPRD 2011; 2:18–25.
- Elbayoumi TA, Torchilin VP: Liposomes for targeted delivery of antithrombotic drugs. Expert Opin. Drug Deliv.2008; 5 1185–1198.
- Torchilin V: Antibody-modified liposomes for cancer chemotherapy. Expert Opin. Drug Deliv.2008; 5: 1003–1025.
- Alexander A, Dwivedi S, Ajazuddin, T.K. Giri TK, Saraf S, Tripathi DK: Approaches for breaking the barriers of drug permeation through transdermal drug delivery. J. Control. Release 2012; 164: 26–40.
- Panwar AS, Upadhyay N, Bairagi M, Gujar S, Darwhekar GN, Jain DK: Emulgel: a review, Asian J. Pharm. Life Sci.2011;1:2231–4423.
- Sarisozen C, Vural I, Levchenko T, Hincal AA, Torchilin VP: PEG-PE-based micelles co-loaded with paclitaxel and cyclosporine A or loaded with paclitaxel and targeted by anticancer antibody overcome drug resistance in cancer cells. Drug Deliv.2012; 19: 169–176.
- Kumar NPM, Patel MR, Patel KR, Patel NM: Emulgels: a novel approach to topical drug delivery. Int. J. Univ. Pharm. Bio Sci. 2013; 2: 134–148.
- Hu L, Yang J, Liu W, Li L: Preparation and evaluation of Ibuprofen-loaded microemulsion for improvement of oral bioavailability. Drug Deliv. 2011; 18: 90–95.
- Kang SN, Lee E, Lee MK, Lim SJ: Preparation and evaluation of tributyrin emulsion as a potent anti-cancer agent against melanoma. Drug Deliv.2011; 18: 143–149.
- Shahin M, Hady SA, Hammad M, Mortada N: Novel jojoba oil-based emulsion gel formulations for clotrimazole delivery. AAPS PharmSciTech 2011; 12:239–247.
- Dickinson E: Hydrocolloids as emulsifiers and emulsion stabilizers. Food Hydrocolloids 2009; 23: 1473–1482.
- Jain A, Gautam SP, Gupta Y, Khambete H, Jain S: Development and characterization of ketoconazole emulgel for topical drug delivery. Pelagia Res. Libr. 2010; 1: 221–231.
- Ajazuddin A, Alexander J, Khan TK, Giri DK, S. Saraf ST: Advancement in stimuli triggered in situ gelling delivery for local and systemic route. Expert Opin. Drug Deliv.2012; 9: 1573–1592.
- Shingade GM, Aamer Q, Sabale, Grampurohit ND, Gadhave MV: Review on: recent trend on transdermal drug delivery system. J. Drug Dev. Ther.2012; 2 (1): 66–75.
- Beitz JM: Heparin induced thrombocytopenia syndrome bullous lensions treated with trypsin-balsam of peru-castor oil ointment: a case study. Ostmony Wound Manage. 2005; 51: 52–54.
- Jager S, Laszczyk MN, Scheffler A: A preliminary pharmatokinetic study of Betulin, the main pentacyclic triterpene from extract of outer bark of birch. Molecules 2008; 13: 3224–3235.
- Maissa C, Guillon P, Simmons P, Vehige J: Effect of castor oil emulsion eye drops on tear film composition and stability. Contact Lens Anterior Eye 2010; 2: 76–82.
- Zhu K, Zhou H, Qian H: Antioxidant and free radical-scavenging activities of wheat germ protein hydrolysates (WGPH) prepared with alcalase. Process. Biochem.2006; 41:1296–1302.
- Lawrence MJ, Rees GD: Microemulsion based media as novel drug delivery systems. Adv. Drug Deliv. Rev2000; 45: 89–121.
- Podlogar F,Gasperlin M, Tomsic M, Jamnik A, Rogac BM:Structural characterization of water-tween 40/Imwitor 308-isopropyl myristate microemulsions using different experimental methods. Int. J. Pharm. 2004; 276:115–128.
- Tomsic M, Podlogar F, Gasperlin M, Rogac BM, Jamnik A: Water-Tween 40/Imwitor-isopropyl myristate microemulsions as delivery system for ketoprofen: small angle X-ray scattering study. Int. J. Pharm. 2006; 327:170–177.
- Nandi I, Bari M, Joshi H: Study of isopropyl myristate microemulsion systems containing cyclodextrins to improve the solubility of 2 model hydrophobic drugs. AAPS Pharm. Sci. Technol. 2003; 4: 71–79.
- Tipton DA, Lyle B, Babich H, Dabbous MK: In vitro cytotoxic and anti-inflammatory effects on human gingival fibrobast and epithelial cells. Toxicol. Vitr. 2003; 17: 301–310.
- Machmudah S, Kawahito Y, Sasaki M, Got M: Supercritical carbon dioxide extraction of rosehip seed oil: fatty acid composition and rose hip optimization. J. Supercrit. Fluids 2007:41: 421–428.
- Kirkeskov B, Christensen R, Bugel S, Bliddal H, Christensen LP, Anders JR: The effect of rose hip on plasma antioxidative activity and C-reative protein in patients with rheumatoid arthritis and normal control: a prospective cohort study. Phytomedicine2011; 18: 953–958.
- Karabacak M, Kanbur M, Eraslan G, Sanca ZS: The antioxidant effect of wheat germ oil on subchronic comaphos exposure in mice. Ecotoxicol. Environ. Saf. 2011; 74: 2119–2125.
- Malecka M: Antioxidant properties of unsaponificable material extracted from tomato seeds, oat grain and wheat germ oil. Food Chem. 2002; 79: 327-300.
- Jing F, An X, Shen W: The characteristics of hydrolysis of triolein catalyzed by wheat germ lipase in water in oil microemulsions. J. Mol. Catal. B Enzym.2003; 24–25: 53–60.
- Vilasau J, Solans C, Gómez MJ, Dabrio J, Mújika-Garai R, Esquena J: Phase behaviour of a mixed ionic/nonionic surfactant system used to prepare stable oil-in-water paraffin emulsions. Colloids Surf., A Physicochem. Eng. Asp.2011; 384: 473–481.
- Baibhav J, Singh G, Rana AC, Saini S: Development and Characterization of Clarithromycin Emulgel for topical delivery. IJDDR, 2012; 4(3): 310-323.
- Khullar R, Kumar D, Seth N, SainiSeema: Formulation and evaluation of mefenamic acid emulgel for topical delivery. Saudi Pharmaceutical Journal, 2012; 20: 63–67.
- Prajapati Mehulkumar N, Patel M R, Patel K R and Patel N M: Emulgels: a novel approach to topical drug delivery. IJUPBS 2013; 2(1): 134- 148.
- Patel RP, Patel G, Baria A: Formulation and evaluation of transdermal patch of aceclofenac. Int. J. Drug Del. 2009; 1: 41 – 51.
- Baibhav J, Singh G, Rana C., Saini S, Singla V: Emulgel: A Comprehensive Review on The Recent Advances In Topical Drug Delivery, International Research Journal of Pharmacy.2011; 2(11); 66-70.
- Perioli L, Ambrogi V, Venezi L, Giovangoli S, Panago C: Formulation studies of benzydamine mucoadhesive formulations for vaginal administration. Drug Dev. Ind. Pharm2009; 35:769–779.
- Deveda P, Jain A, Vyas N, Khambete H, Jain S: Gellified emulsion for sustained delivery of itraconazole for topical fungal diseases. Int. J. Pharm. Pharm. Sci. 2010; 2: 104–112.
- Khullar R, Kumar D, Seth N, Saini S: Formulation and evaluation of mefenemic acid emulgel for topical delivery. Saudi Pharm. J. 2011: 63–67.
- Mohamed MI: Optimization of chlorphenesin emulgel formulation. AAPS Pharm. Sci. Technol. 2004;6:534–542.
- El-Setouhy DA, El-Ashmony SM: Ketorolac trometamol topical formulations: release behaviour, physical characterization, skin penetration, efficacy and gasteric safety. J. Pharm. Pharmacol.2010; 62: 25–34.
- Shahin M, Hady SA, Hammad M, Mortada N: Novel jojoba oil based emulsion gel formulations for clotrimazole delivery. AAPS Pharm. Sci. Technol.2011; 12: 239–247.
- Shokri J, Azarmi S, Fasihi Z: Effect of various penetration enhancers on percutaneous absorption of piroxicam from emulgel.Res. Pharm. Sci.2012; 7:225–2234.
- Perioli L, Panago C, Mazzitelli S: Rheological and functional characterization of new anti-inflammatory delivery system designed for buccal administration. Int. Pharm. 2008; 356: 19–28.
- Baibhav J, Singh G, Rana A C, Saini S, Singla V: Emulgel: A comprehensive review on recent advancement on topical drug delivery. IRJP, 2011; 2(11): 66-70.
- Aher S. D, Banerjee S.K, Gadhave M.V, Gaikawad D.D: Emulgel: a new dosage form for topical drug delivery.IJIPLS. 2013; 3(3): 1-10.
- Prajapati Mehulkumar N, Patel M R, Patel K R and Patel N M: Emulgels: a novel approach to topical drug delivery. IJUPBS. 2013; 2(1): 134-148.
- Panwar AS, Upadhyay N, Bairagi M, Gujar S, Darwhekar GN, Jain DK. Emulgel: A review. Asian J Pharm Life Sci. 2011; 1(3): 333-343.
- Garg A, Aggarwal D, Garg S, and Singla AK (2002). Spreading of Semisolid Formulations: An Update. Pharmaceutical Technology. Circle/eINFO 74. Available at:http://www.pharmtech.com/pharmtech/data/articlestandard//pharmtech/362002/ 30365/article.pdf
- Khalil YI, Khasraghi AH, Mohammed EJ. Preparation and evaluation of physical and, rheological properties of clotrimazole emulgel: Iraqi J Pharm Sci. 2011; 20(2): 19-27.
- Baibhav J, Singh G, Rana C, Saini Seema, Singla Vikas,: Emulgel: A Comprehensive Review on The Recent Advances In Topical Drug Delivery, International Research Journal of Pharmacy. (2011; 2(11): 66-70.
- Trommer H, Neubert RHH: Overcoming the stratum corneum the modulation of skin penetration. Skin Pharmacol Physiol.2006; 19:106-121.
- Singla V, Saini S, Joshi B, Rana A.C, : Emulgel: A New Platform for Topical Drug Delivery International Journal of Pharma and Bio Sciences, 3(1); 21-29.
- Washitake M, Takashima Y, Tanaka S, Anmo T, Tanaka I Drug permeation through egg shell membranes. Chern. Pharm.1980; 28:2855-2861.
- ICH Harmonized Tripartite Guidelines, Stability Testing of New Drug Substances and Products. ICH Committee 2003; 8.
- Singh J, Gupta S, Kaur H. Prediction of in vitro drug release mechanisms from extended release matrix tablets using SSR/R2 Trends in applied science research 2011;6(4) :400-409.
- Pinheiro IM, Carvalho IP, de Carvalho CES, Brito LM, da Silva ABS, Conde Júnior AM, et al. Evaluation of the in vivo leishmanicidal activity of amphotericin B emulgel: An alternative for the treatment of skin leishmaniasis. Exp Parasitol 2016; 164; 49-55.
- Singh VK, Yadav I, Kulanthaivel S, Roy B, Giri S, Maiti TK, et al. Groundnut oil based emulsion gels for passive and iontophoretic delivery of therapeutics. Des Monomers Polym 2016:1-12.
- Zhang H, Cui B, Qian X, Fan H, Feng X. Preparation of amlodipine besylate emulgels for transdermal administration and its percutaneous permeability in vitro. Chin J New Drugs 2016; 25(3).
- Jacobs GA, Gerber M, Malan MM, Du Preez JL, Fox LT, Du Plessis J. Topical delivery of acyclovir and ketoconazole. Drug Deliv 2016; 23(2):641-651.
- Soliman SM, Abdelmalak NS, El-Gazayerly ON, Abdelaziz N. Novel non-ionic surfactant proniosomes for transdermal delivery of lacidipine: optimization using 23 factorial design and in vivo evaluation in rabbits. Drug Deliv 2016:1-15.
- Burger C, Gerber M, Du Preez JL, Du Plessis J. Optimised transdermal delivery of pravastatin. Int J Pharm 2015; 496(2):518-525.
- Mallick SP, Sagiri SS, Singh VK, Behera B, Thirugnanam A, Pradhan DK, et al. Genipin-Crosslinked Gelatin-Based Emulgels: an Insight into the Thermal, Mechanical, and Electrical Studies. AAPS PharmSciTech 2015; 16(6):1254-1262.
- Nivsarkar M, Maroo SH, Patel KR, Patel DD. Evaluation of skin penetration of diclofenac from a novel topical non aqueous solution: A comparative bioavailability study. J Clin Diagn Res 2015; 9(12):FC11-FC13.
- Hamed R, Basil M, AlBaraghthi T, Sunoqrot S, Tarawneh O. Nanoemulsion-based gel formulation of diclofenac diethylamine: design, optimization, rheological behavior and in vitro diffusion studies. Pharm Dev Technol 2015.
- Daudt RM, Back PI, Cardozo NSM, Marczak LDF, Külkamp-Guerreiro IC. Pinhão starch and coat extract as new natural cosmetic ingredients: Topical formulation stability and sensory analysis. Carbohydr Polym 2015; 134:573-580.
- Dong L, Liu C, Cun D, Fang L. The effect of rheological behavior and microstructure of the emulgels on the release and permeation profiles of Terpinen-4-ol. Eur J Pharm Sci 2015; 78:140-150.
- Kong X, Zhao Y, Quan P, Fang L. Development of a topical ointment of betamethasone dipropionate loaded nanostructured lipid carrier. Asian J Pharm Sci 2015.
- Digennaro R, Pecorella G, La Manna S, Alderisio A, Alderisio A, De Pascalis B, et al. Prospective multicenter observational trial on the safety and efficacy of LEVORAG® Emulgel in the treatment of acute and chronic anal fissure. Tech Coloproctol 2015;19(5):287-292.
- Shen Y, Ling X, Jiang W, Du S, Lu Y, Tu J. Formulation and evaluation of Cyclosporin A emulgel for ocular delivery. Drug Deliv 2015;22(7):911-917.
- Pednekar A, Dandagi P, Gadad A, Mastiholimath V. Formulation and characterisation of Meloxicam loaded emulgel for topical application. Int J Pharmcy Pharm Sci 2015;7(11):216-222.
- Singh C, Sharma P, Bal T, Ghosh M, Dubey R, Das S. Preparation and evaluation of Radiosensitizing agent Nimorazole in topical emulgel. Der Pharm Lett 2015;7(9):132-142.
- Nikumbh KV, Sevankar SG, Patil MP. Formulation development, in vitro and in vivo evaluation of microemulsion-based gel loaded with ketoprofen. Drug Deliv 2015;22(4):509-515.
- Naga Sravan Kumar Varma V, Maheshwari PV, Navya M, Reddy SC, Shivakumar HG, Gowda DV. Calcipotriol delivery into the skin as emulgel for effective permeation. Saudi Pharm J 2014;22(6):591-599.
- Phutane KR, Patil SS, Adnaik RS, Nitalikar MM, Mohite SK, Magdum CS. Design and development of allopurinol emulgel. Res J Pharm Technol 2014;7(7):733-736.
- Sabu KR, Basarkar GD. Formulation, development and in-vitro evaluation of Terbinafine hydrochloride emulgel for topical fungal infection. Intl J Pharm Sci Rev Res 2013;21(2):168-173.
- Ghodekar SV, Chaudhari SP, Ratnaparakhi MP. Development and characterization of silver sulfadiazine emulgel for topical drug delivery. Int J Pharmcy Pharm Sci 2012;4(4):305-316
- Shokri J , Azarmi Sh, Fasihi Z, Hallaj-Nezhadi S, Nokhodchi A, Javadzadeh Y. Effects of various penetration enhancers on percutaneous absorption of piroxicam from emulgels. Res Pharm Sci 2012; 7(4):225-234.
- Ibrahim MM, Shehata TM. The enhancement of transdermal permeability of water soluble drug by niosome-emulgel combination. J Drug Deliv Sci Technol 2012; 22(4):353-359.
How to cite this article:
Kumar D, Singh J, Antil M and Kumar V: Emulgel-novel topical drug delivery system–a comprehensive review. Int J Pharm Sci Res 2016; 7(12): 4733-42.doi: 10.13040/IJPSR.0975-8232.7(12).4733-42.
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Article Information
3
4733-4742
486
3901
English
IJPSR
Davinder Kumar, Jasbir Singh, Mamta Antil and Virender Kumar *
College of Pharmacy, Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, University of Health Sciences, Rohtak, Haryana, India
sachdeva.virender5@gmail.com
22 June, 2016
26 October, 2016
16 November, 2016
10.13040/IJPSR.0975-8232.7(12).4733-42
01 December, 2016