Topical Drug Delivery

Topical drug delivery is the best and special route for local and systemic delivery of therapeutic agent due to its advantages and affordability. Conventional dosage forms were not able to give quick action to the desired area or system. At this stage, novel formulation like hydrogel comes into existence. Hydrogels are cross-linked polymeric three dimensional structure of hydrophilic group that can swell and shows it action due to environmental changes. Though, determining the absorption of drug at the site of action or skin layer by using topical preparations or product is a big task for researcher. Release of drug via topical route symbolize a most suitable and novel approach. Conventional topical dosages forms have not provide any evidence to be useful in topical drug delivery. Novel drug delivery systems show a great potential for topical delivery. To defeat the problems related with conventional delivery devices, polymeric gels such as hydrogels have been recommended. Hydrogels have been extensively used as the transporter for drug delivery systems. These biomaterials have increase interest due to their characteristics like swelling in aqueous solution, pH and temperature sensitivity and biocompatibility. The objective of this review article to highlights the classification of hydrogel, their advantages, disadvantages, preparation method of hydrogel, characterization of hydrogel and application of hydrogels. This review disclose the convenience of hydrogel as a topical drug delivery systems used in the body by the ophthalmic route, rectal route, vaginal route and skin.

4 . The topical drug delivery system allows its usage where the others system of drug administration fails or it is mainly used in fungal infection. Human skin is a uniquely engineered organ that permits terrestrial life by regulating heat and water loss from the body whilst preventing the ingress of noxious chemicals or microorganisms. It is also the largest organ of the human body, providing around 10% of the body mass of an average person, and it covers an average area of 1.7 m 2 .Whilist such a large and easily accessible organ apparently offers ideal and multiple sites to administer therapeutic agents for both local and systemic actions, human skin is a highly efficient self-repairing barrier designed to keep the insides in and the outside out 5 . Gels being newer class of dosage form are created by entrapment of large amounts of aqueous or hydro alcoholic liquid in a network of colloidal solid particles, which may consist of inorganic substances, such as aluminum salts or organic polymers of natural or synthetic origin 6 . The constitution of higher aqueous component permits greater dissolution of drugs, and also permits easy migration of the drug through a vehicle that is essentially a liquid, compared with the ointment or cream base7. All these findings make them superior in terms of use and patient acceptability. In spite so advantageous gels show a major limitation in the delivery of hydrophobic drugs. So in order to cover up this lacking, emulgel is prepared and used so that even a hydrophobic therapeutic moiety can enjoy the unique properties of gels. In fact, the presence of a gelling agent in the water phase converts a classical emulsion into an emulgel 8 . Both oil-in-water and water-in-oil emulsions are used as vehicles to deliver various drugs to the skin.

CONCLUSION The microsponge delivery system is a technology of controlled release system in which active pharmaceutical ingredient is loaded in the macro porous beads and initiates reduction in side effects with improved therapeutic efficacy. Microsponge can be effectively incorporated into topical drug delivery system like gel, cream etc. for retention of dosage form on skin. It is also use for oral delivery of drugs using bio erodible polymers, especially for colon specific delivery. The microsponge drug delivery system is believed to reduce side effects, improved stability, increased elegance, enhanced formulation flexibility and also offers entrapment of its ingredients. Microsponge systems are non-irritating, non- mutagenic, non-allergenic, and nontoxic. This technology is being used currently in cosmetics, over-the-counter skin care, sunscreens, and prescription products. This kind of drug delivery technology may lead to a better understanding of the healing of several diseases.

Keywords: Recent techniques, Topical drug delivery, TDDS, Advances in skin delivery Introduction Over the last decades the treatment of illness has been accomplished by administrating drugs to human body via various routes namely oral, sublingual, rectal, parental, topical, inhalation etc. Topical delivery can be defined as the application of a drug containing formulation to the skin to directly treat cutaneous disorders like acne or the cutaneous manifestations of a general disease like psoriasis with the intent of containing the pharmacological or other effect of the drug to the surface of the skin or within the skin. Semi-solid formulation in all their diversity dominate the system for topical delivery, but foams, spray, medicated powders, solution, and even medicated adhesive systems are in use. 1 The delivery of a drug to a specific site, topical formulations are probably among the most challenging products to develop. An effective topical formulation needs to provide a stable chemical environment in a suitable dispensing container in order to accommodate multiple compounds that may have different, if not incompatible, physicochemical characteristics.

Quality by Design (QbD) is an approach to the design and development of the formulation by using different scientific strategies, tools and various nanoparticulate data available. QbD can assist the pharmaceutical industry and research scholars to satisfactorily move towards the more scientific, active, risk-based pharmaceutical development. Qbd, if applied, to the entire product cycle minimizes the end product testings and leaves one with safe, effective and quality product. In the present study, an attempt is made to apply the QbD to the Nanosponges for topical drug delivery system; a highly porous nanostructure. They can entrap drug molecules in their aqueous pore such as hydrophilic as well as lipophilic. Nanosponges to enhance the drug stability, to enhance the short half-life due to the shorter half-life. The nanosponges were prepared by the solvent emulsion diffusion method. Nanosponges can be used as a carrier for biocatalysts in the delivery and release of enzymes, proteins, vaccines, and antibodies. Nanosponges have various applications like enhancing bioavailability of drugs and delivery of drugs into oral, topical as well as parenteral routes.

*Corresponding Author: Daisy P.A. India. ABSTRACT For the treatment of local as well as systemic skin disorders, topical drug delivery systems have been used for centuries offering the advantage of delivering the drug directly to the site of action and also delivering the drug for extended period of time at the affected area. When gel and emulsion are used in combined form the dosage form are referred as Emulgel. Since they contain dual control release systems: a gel and an emulsion, emulgels have emerged as one of the most interesting topical delivery system. They are emulsions of either oil-in-water or water in oil type, which are gelled by mixing with a gelling agent. The major objective behind emulgel is delivery of hydrophobic drugs via skin. Thus emulgels have major advantages on novel vesicular system as well as on conventional systems in various aspects. They are referred for topical use due to their favorable properties such as being greaseless, non-staining, thixotropic, emollient, easily removable, water soluble, bio-friendly, long shelf-life, transparent and pleasant appearance. The use of emulgels can be expanded in different classification namely analgesics, anti-inflammatory, anti-fungal, antiacne drugs and various cosmetic formulations.

Emulgels have emerged as one of the most interesting topical delivery system as it has dual release control system i.e. gel and emulsion. The major objective behind this formulation is delivery of hydrophobic drugs to systemic circulation via skin. A unique feature of topical drug delivery is the direct accessibility of the skin as a target organ for the diagnosis and treatment. When gel and emulsion are used in combined form the dosage form are referred as Emulgel. This may be proving better stability and release of drug than simply incorporating drugs into gel base. Other novel approaches like niosomes and liposomes are of nano size and due to vesicular structures may result in leakage and result in lesser entrapment efficiency. But gels due to v ast network have comparatively better loading capacity.

Topical drug delivery system can be defined as direct effects of formulation or drug containing medication to the skin to get localizing effect of drug or directly cure cutaneous disorders. Emulgels has to be used as a topical drug delivery system for hydrophobic drugs. When gels and emulsions are used in combined form the dosage forms are referred as emulgels. Emulgels have emerged as one of the most interesting topical delivery system as it has dual release control system i.e. gel and emulsion. The major objective behind this formulation is delivery of hydrophobic drugs to systemic circulation via skin. In recent years, there has been great interest in the use of novel polymers which can function as emulsifiers and thickeners because the gelling capacity of these compounds allows the formulation of stable emulsions and creams by decreasing surface and interfacial tension and at the same time increasing the viscosity of the aqueous phase. In fact, the presence of a gelling agent in the water phase converts a classical emulsion into an emulgel. Emulgels for dermatological use have several favourable properties such as being thixotropic, greaseless, easily spreadable, easily removable, and emollient, no staining, water-soluble, longer shelf life, and bio-friendly, transparent & pleasing appearance. These emulgels are having major advantages on novel vesicular systems as well as on conventional systems in various aspects. Various permeation enhancers can potentiate the effect. So emulgel formulations can be used as better topical drug delivery systems over present conventional systems available in market.

Debjit Bhowmik 1* , Harish Gopinath 1 , B. Pragati Kumar 1 , S.Duraivel 1 , K.P.Sampath Kumar 2 1.Nimra College of Pharmacy, Vijayawada, Andhra Pradesh, India. 2.Department of pharmaceutical sciences, Coimbatore medical college, Coimbatore Drug delivery systems are methods which are used to ensure that drugs get into the body and reach the area where they are needed. These systems must take a number of needs into account, ranging from ease of delivery to effectiveness of the drugs. Several companies specialize in developing methods of drug delivery, marketing these products to pharmaceutical companies, and other pharmaceutical companies develop their own systems. Many of these methods are patented and proprietary. When a drug is administered, the dosage must be carefully calculated so that the body can use the drug, which requires a drug delivery system which allows for precise dosing. Drug delivery systems also need to consider the way in which a drug is metabolized by the body. For example, some drugs are destroyed in the intestinal tract, which means that they cannot be introduced to the body in this way. Others may be dangerous in large amounts, which means that a time release method should be used to deliver the drug for patient safety. Topical drug delivery systems involve the introduction of a drug to the surface of the body, in a formulation which can be absorbed. Skin patches are an example of topical drug delivery systems. Other systems involve sprays applied to the mucus membranes of the nose, inhalation aerosols, eye drops, or creams which may be rubbed into the skin. These systems are often very easy for patients to use, which makes them appealing.In all cases, the goal of a drug delivery system is to get the right dosage to the right place. Patients tend to prefer methods which are painless and easy, which is why many pharmaceuticals come in the form of topical and enteral methods which can be taken by mouth or applied directly to the skin. In clinical environments, perenteral routes can be more common, especially for controlled substances, because these methods allow for greater control over how and when the drugs are used.

ABSTRACT Niosomes are vesicular drug delivery system; it acts as a carrier and protects the drug from the internal environment. It has been also used because of its higher diffusivity in skin for promoting dermal delivery of drug which has to act topically. The aim of present study is to developed and characterise topical drug delivery system containing niosome by using antifungal agent. The antifungal agent widely used for the treatment of infection due to fungal species like Trichophyton rubum, Trichophyton mentagrophyts, Malassezia furfur etc. most of the antifungal drug are poorly water soluble. Sustained release of Niosomes can be applied to drugs with low water solubility since those could be maintained in the circulation via niosomal encapsulation. Niosomes were formulated by rotary evaporation hydration method by using phospholipids, cholesterol and Non ionic surfactant such as span and Tween. Primary placebo batches of niosome were prepared and evaluated for particle size and shape. Then octopirox loaded batches of niosome were prepared and evaluated for size, shape and Entrapment efficiency. For the delivery of niosome through skin topical dosage form i.e. cream was prepared. Evaluation of cream containing niosome was carried out for viscosity, measurement of pH, spreadability etc. the results obtained are shown in the present work. From the results it can be concluded that the formulation evaluated for the drug release of the optimized batch i.e. V- using o/w cream base, it was concluded that the drug release rate increases with its increasing concentration.

www.ijpsr.com DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.7 (12).4733-42 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

Liposome is has been used in topical drug delivery system because of its much higher diffusivity in skin compared to most bare. Liposomal formulations are widely used in the pharmaceutical field as drug delivery systems due to their versatility and clinical efficacy and they have been used to administer drugs by several routes such as the oral, parenteral, and topical. Among these, topical delivery of drugs carried by liposomes exhibits interesting applications, not only for promoting dermal delivery of drugs which have to act topically, such as local anaesthetics, but also for enhancing topical delivery of drugs intended for systemic use, thus more effectively exploiting this non- invasive alternative route to oral administration.

Together with excellent dispersibility in aqueous solu- tion, ND may have ideal properties as a permeation enhancer for topical drug delivery systems. In order to avoid adverse effects of permeation enhancers in topical formulations, they need to be noninvasive while facilitating permeation of drugs through the skin. 19 In general, nanoparticles that have sizes 20 nm are known to poorly penetrate the skin. 20 Although the single particle size of ND is ~ 5 nm, ND exists as particles of ~ 50–100 nm called agglutinates, which poorly permeate the skin. 21 The adsorption of drugs on the surface of well-dispersed ND particles may be very attractive, since ND could function as a “drug-reservoir or matrix” agent for topical drug delivery. 22 Additionally, ND was reported as a ultraviolet (UV) filter and photostability enhancer for drugs by absorbing and scattering light. 23,24 Antioxidant properties of ND were also reported, which act by promoting oxygen reduction. 25,26 These properties of ND could expand their applicability as a formulation stabilizer.

Keywords: fi lm-forming solution, fi lm-forming polymer, topical drug delivery Introduction Topical routes of drug delivery aim for systemic or local effects and offer various advantages, including avoiding fi rst-pass metabolism and the effect of low pH and enzymes in the gastrointestinal tract, as well as a large available surface area. 1–7 To improve therapeutic ef fi ciency or pharmacokinetic pro fi les, drugs administered via the topical route are generally made in a dosage system, such as a patch, gel, lotion, cream, ointment, or spray. 8 – 10 However, the concern is that patch preparations still leave drug residues after use and can be deliberately abused. 11 Patch preparations are also often associated with hypersensitivity, irritation, and blistering. 12 Problems in the scale-up of production are also often found where drugs are dif fi cult to stabilise and can crystallise during storage. 13 Other semisolid preparations also have the disadvantage of being easily attached to clothing while on the move and can cause cross-infection of wounds because it is applied using the fi ngers. 14 Compared to other topical dosages, sprays offer several advantages such as prac- tical use, low incidence of irritation, sterility of the dosage, excellent coverage of the skin or wound, even distribution of the drug when applied, and adjustable dosage. 14–20

* E mail: joshivaibhav88@gmail.com ABSTRACT Emulgel has emerged as a promising drug delivery system for the delivery of hydrophobic drugs. When gel and emulsion are used in combined form they are referred as Emulgel. Emulsion in gel have emerged as one of the most interesting topical drug delivery system as it have dual release control system i.e. emulsion and gel. Gels are relatively newer class of dosage form created by entrapment of large amount of aqueous or hydro alcoholic liquid in a network of colloidal solid particles which may consist of inorganic substances or organic polymers of natural or synthetic origin. In recent years there has been great interest in the use of novel polymers with complex function such as emulsifiers and thickeners. The gelling capacity of these compounds allows the formulation of stable emulsion and creams by decreasing surface and interfacial tension at the same time increasing the viscosity of aqueous phase. In spite of many advantages of gels a major limitation is in the delivery of hydrophobic drug. So to overcome this limitation an emulsion based approach is being used so that even a hydrophobic moiety can enjoy the unique property of gel.

ABSTRACT KARADZOVSKA, DANIELA. High Throughput Approaches to Assess Formulation Effects on Topical Drug Delivery. (Under the direction of Dr. Jim Riviere). Conventional in vitro and in vivo techniques used in the assessment of the rate and extent of topical drug absorption are neither high throughput nor economical. Further complications arise due to the ethical concerns associated with the use of experimental animals or human volunteers. Coupling all this with the vast variation in drug-vehicle combinations possible and available for testing, the task of evaluating all combinations is virtually impossible. Therefore, three specific approaches were evaluated as high throughput solutions; an in silico approach (quantitative structure-permeability relationship (QSPeR) model) and two novel in vitro techniques (membrane coated fiber (MCF) array and skin- parallel artificial membrane permeability assay (PAMPA)). The performance of each method was compared to a comprehensive data set generated as part of this project using the

The studies were conducted with an object to develop even, harmless and efficient delivery system for Fluticasone Propionate. Topical drug delivery has gained a marvellous interest in today’s pharmaceutical formulation and research is going on in achieving better product. Fluticasone Propionate is corticosteroids with anti-inflammatory medication that is generally used to treat eczema and dermatitis. Emulgel is a semi solid preparation which decreases the systemic side effects and to create a more pronounced effect with lower doses of the drug. Emulsion in gel have emerged as one of the most interesting topical drug delivery system as it has twofold release control system. Also the stability of emulsion is increased when it is incorporated into gel. The Emulgel was developed using polymers like Carbopol 934 and HPMC K-100 in various ratios of gel and emulsion. DSC and IR spectral studies were performed to confirm the compatibility of drug and polymers in the formulations. The prepared Emulgel was evaluated for their physical appearance, pH evaluation, spreadability, rheological study, and drug content and in- vitro permeation studies. All formulation was evaluated for their release patterns. The result indicates that Emulgels offers better release, controlled release, or a stable atmosphere for the incorporated drug (Fluticasone Propionate).

Topical drug delivery system can be defined as direct effects of formulation or drug containing medication to the skin to get localizing effect of drug or directly cure cutaneous disorders. The skin has evolved to prevent excessive water loss from the internal organs and to limit the ability of xenobiotics and hazardous substances to enter the body. Notwithstanding this barrier function, a number of strategies have been developed by scientists to deliver drugs to and through the skin. Skin as an important site for topical effects so there is considerable interest in the skin for local and systemic effect of drug application. However, in the skin, the stratum corneum is the main barrier for drug penetration there by limiting topical and transdermal bioavailability. Skin penetration enhancement techniques have been developed to improve bioavailability and increase the range and number of drugs available for both topical and transdermal delivery. In this review, we have discussed about the various penetration enhancers, their mechanism of action and their potential for clinical application. Keywords: Topical Drug Delivery, Skin, Stratum Corneum Modification, Penetration Enhancers, Bioavailability.

Mahaparale et al.: Terbinafine Hydrochloride Polymeric Microsponges The objective of the present study was to develop and evaluate sustained delivery of terbinafine hydrochloride from topical polymeric microsponges. Microsponges of ethyl cellulose containing terbinafine hydrochloride were prepared by quasi emulsion solvent diffusion method. Effect of drug polymer ratio on active drug content, particle size and entrapment efficiency were studied. Drug polymer ratio greatly affects properties (entrapment efficiency, active drug content, particle size) of microsponges. Terbinafine hydrochloride microsponges showed highest actual drug content, entrapment efficiency and smaller particle size, so 1.5:1 ratio of drug and polymer was selected for optimization study. Optimization study was carried out by taking internal phase volume, stirring rate, emulsifier concentration as independent variables and their effects on entrapment efficiency, particle size were studied. It was found that as stirring speed increases, the particle size decreases and entrapment efficiency increases, while as volume of dichloromethane increases, particle size decreases. Morphology of obtained microsponges was revealed by scanning electron microscope and was found to be porous and spherical. Optimized formulation of microsponge was dispersed in Carbopol gel and evaluated for drug content, pH, viscosity and in vitro drug release. Release of drug was found to be sustained through microsponge gel as compared to marketed product and pure drug gel. Ex vivo drug deposition study was carried using rat abdominal skin. Drug deposition was found to be satisfactory. Prepared polymeric microsponges could be a potential topical drug delivery system in antifungal therapy.

Pande, et al.: Formulation of Sertaconazole Nitrate Microsponges Present study was taken up to develop a topical formulation that releases the drug in controlled manner, reduce the side effects associated with topical drug delivery and improve product efficacy with aid of microsponges. Microsponges loaded with sertaconazole nitrate were prepared by using quasi emulsion solvent diffusion with five different proportions of the polymer (Eudragit RS 100). The developed microsponges were analyzed for particle size, production yield, entrapment efficiency and drug content. Scanning electron microscopic images of microsponges revealed that they are spherical in shape and contain pores. Pore structure analysis was done by using mercury intrusion porosimetry technique, which confirmed the porous nature of microsponges. Microsponges were then incorporated in to a 1% corbopol gel and evaluated for pH, drug content, texture profile analysis and in vitro drug release. The batch F IV was found to be optimal as it shown 69.38% controlled drug release in 8 h that followed Higuchi model.