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gels) or organic solvent based (organogels). Pastes: are semisolid dosage forms that contain one or more drug substances incorporated in a base with large proportions of finely dispersed solids, are intended for external application to skin, but very thick & stiff. Jellies: are transparent, non-greasy, semisolid preparation for external applications to skin & mucous membrane. Poultices: are soft, viscous wet masses of solid substances applied to skin & now outdated. Suppositories: are intended in other than oral cavity i.e., vaginal, nasal cavity. Generally introduced in systemic. Percutaneous drug absorption: Semisolid dosage forms for dermatological drug therapy are intended to produce desired action at specific sites in the epidermal tissue. A drugs ability to penetrate the skins epidermis, dermis and subcutaneous fat layers depends on the properties of the drug and the carrier base. Although drug and the carrier base. Although drug and the carrier base. Although area for most dermatological disorders lies in the viable epidermis or upper dermis. Hence, a drugs diffusive penetration of the skin percutaneous absorption is an important aspect of drug therapy. The main portals of drug entry are the follicular region, the sweat ducts or the unbroken stratum corneum between the appendages. A substances particular route mainly depends on the physicochemical properties of the drug and the condition of the skin.
Submicron emulsion vehicle system. Conventional creams have a mean droplet size ranging from 10 to100 m. Such formulations have demonstrated poor penetration of drug-loaded oil droplets into deep skin layers. It has been reported that microparticles with diameters penetrate follicular ducts, whereas penetrate follicular ducts, whereas particles 10 m remain on the skin surface, and those 3 m are distributed randomly into hair follicles and stratum corneum .Taking these constraints into consideration, researchers have developed the submicron emulsion vehicle system (SMEVS) for improving drug permeation. The submicron lipid particles of an SMEVS penetrate the layers of the stratum corneum, increasing its fluidity and leading to the disruption of barrier continuity. Significant hydration of the stratum corneum, assisted by gap formation, permits the penetration of submicron emulsion particles by forming a drug depot in the skin. The result is slow, continuous, and controlled systemic delivery of the drug. An SMEVS can be formulated by processing a medium-chain triglyceride emulsion with a high pressure homogenizer. In addition, the presence of lecithin, an efficient dispersing agent, causes a drastic reduction in droplet size, usually to between 100 and 300 nm. Gels with permeation enhancers. Skin can act as a barrier to the deeper penetration of drug molecules. With the introduction of various penetration enhancers, however, systemic drug delivery through the transdermal route has gained major footing. These chemicals, incorporated in a suitable drug-carrying semisolid vehicle, enhance the amount of drug permeation through skin. The high diffusion rates of indomethacin and diclofenac show that lecithin microemulsion gel is a suitable matrix for transdermal drug delivery. Localized drug delivery. Localized drug delivery by semisolid dosage forms continues to be a major area of research. Advances in formulation approaches have led to increased drug stability as well as improvement in the aesthetic appeal of semisolid dosage forms. Oleo-hydrogel systems. Oleo- hydrogel systems for localized skin have been explored successfully. Rhee et al. examined transdermal permeation using various vehicle systems to avoid systemic side effects and gastrointestinal irritation from ketoprofen upon oral administration. The researchers examined an oleo-hydrogel system that consisted of ketoprofen incorporated into an emulsion of oil and carbomer hydrogel mixture, with Nmethylpyrrolidone as a permeation enhancer. The greater bioavailability of ketoprofen in the oleo-hydrogel system was ascribed to good drugrelease properties, higher emulsion droplet stability of the carbomer gel, and the penetration-enhancing effect of Nmethylpyrrolidone. The formulation of ketoprofen oleohydrogel that showed maximum percutaneous absorption was one that contained 3% ketoprofen, 1% carbomer, 10% Nmethylpyrrolidone, 10% oils, 8% surfactant, and water adjusted to pH 4.6 using triethanolamine. Volatile vehicleantinucleant polymer systems. Studies have investigated various techniques to enhance the transdermal permeation of topically applied drug molecules. Increasing the thermodynamic activity of drug molecules was found to be the most efficient approach. This increase can be achieved by the volatile vehicleantinucleant polymer system Enhanced permeation of sodium nonivamide acetate (an antinociceptive agent) was observed with ethanolbuffer solutions (pH 4.2) containing antinucleant polymers. The system used
supersaturation (achieved by evaporation of the vehicle) for penetration enhancement. In supersaturated solutions the drug is in a high state of activity and has a great leaving tendency, resulting in increased flux. Lecithin microemulsion gel. Lecithin microemulsion gel is a promising matrix system for transdermal drug delivery .Microemulsion gels are obtained by dispersing soybean lecithin (a mixture of phosphatidyl cholines) in a nonpolar organic solvent, thereby forming an entangled network of long and flexible multimolecular aggregates. Fatty-acid esters such as isopropyl palmitate are preferred organic solvents because of their relatively high viscosity and complete optical transparency. Cream containing lipid nanoparticles. For enhanced penetration of topical drugs, occlusion of skin is the prime criterion. This requirement can be achieved easily by the incorporation of large quantities of fats and oils, especially liquid and semisolid paraffin. However, such formulations have the limitations of poorcosmetic properties characterized by a greasy feel and glossy appearance.The development of a water-in-oil cream wherein the aqueous phase was divided into small droplets solved this problem. Solid lipid nanoparticles. Solid lipid nanoparticles of glyceryl behenate have been investigated as efficient carrier systems for topical use . They provide both burst and sustained drug release. Burst release improves the penetration of drug into the skin. Solid lipid nanoparticles possess the advantages of better drug penetration because the small particle size of their drug-carrier system ensures close contact to the stratum corneum and increases the amount of encapsulated drug penetrating the skin. Liposomes as drug carriers. Liposomes have shown great potential as novel drug carriers for dermal and transdermal systems. Liposomes are microscopic vesicles composed of membranelike lipid layers surrounding an aqueous compartment They also serve as a reservoir for the prolonged release of drugs within various skinlayers , thereby reducing the rapid elimination of drug into the blood or lymphatic circulation.
Advantages of Novel Approaches: Carriers like liposomes delivers drug in to the dermal & transdermal systems & retained for providing the prolonged release of drugs. SLN provide sustained drug release also better penetration of drugs because the small particle size of their drug-carrier system ensures close contact to the stratum corneum and increases the amount of encapsulated drug penetrating the skin. Microemulsion gels are used for systemic drug delivery. i.e., lecithin microemulsion gel. Ethosomes, cubosomes are used for cosmetics due to their better penetration in the stratum corneum. iontophoresis, electoporation and phonosoresis are used to deliver ionic drugs, in systemic circulation. oleo-hydrogel used for local action to avoid systemic side effects.
Disadvantages: Their production cost is high. Not available easily. Generally low efficacy.
So, novel approaches of semisolid dosage form can be classified according to there approaches: A) BIOLOGICAL MEANS
1. Nanoparticles Used In Dermal Application Nanoparticulate systems able to control release and to improve targeting to skin are innovative common topics both in pharmaceutical and cosmetic field. Liposomes are of course the best known nanoparticulate systems. Several studies demonstrated their efficacy as drug delivery systems for topical administration ways The well characterized liposome vesicles can host different molecules in the bilayer, on the surface or in the inner of their structure. Since liposome composition and structure strictly resemble to the stratum corneum, percutaneous administration of this vehicle leads to deposition of lipidic components from which liposome load can be slowly release. As an alternative to liposome, solid lipid nanoparticles (SLN) represent innovative drug carrier systems firstly designed for i.v. administration and recently investigated for transdermal application. Many studies have been demonstrated the efficiency of liposomes as drug carriers for different administration ways. Nevertheless liposomes are
characterized by some drawbacks such as the limited physical stability. Recently some alternative nanodispersed systems have been developed, such as SLN, Ethosomes and cubosomes. SLN possess interesting features as nanotechnology systems for a wide spectrum of application. Their solid matrix allows protection of chemically labile agents from degradation. The use of SLN in dermatics seems very attractive due to the lipophilic character of their components improved skin hydration is conferred due to adhesive and coherent film formation exherting occlusive properties. Moreover, SLN may also enhance the effects of active compounds in cosmetics. Ethosomes are attracting systems able to solubilize different kind of molecules and to enhance their delivery through the skin due to the presence of ethanol. Moreover their physical stability improves their use with respect to liposomes. Bicontinuous cubic liquid crystalline phases, either in bulk or cubosome form, offer unique properties of particular interest to the personal care industry. Cubic phase materials can be formed by simple combination of biologically compatible lipids and water and are thus well-suited for use in treatments of skin, hair, and other body tissue. Dermal application of personal care products containing cubosomes is particularly interesting due to the possible stratum corneumcubosome interaction recently demonstrated. 2.Liposomes Liposomes were discovered in the early 1960s and subsequently studied as cell membrane models. They have since gained recognition in the field of drug delivery. The particle size of liposomes ranges from 20 nm to 10 m in diameter. Liposomes vary in charge and in size depending on their manufacturing protocol and type of (phospho) lipid bilayer used (the small unilamellar vesicle [SUV] size range is 0.02 -0.05 m, the large unilamellar vesicles [LUV] size range is greater than 0.06 m and the multilamellar vesicle [MLV] size range is 0.1 0.5 m). The physicochemical characteristics of the liposomes, like particle size, lamellarity, surface charge, sensitivity of pH changes and bilayer rigidity can be manipulated. Liposomes showed promising result in the drug delivery but their applicability is limited primarily to specific use because of short half-life in blood circulation. The circulation time of liposomes in the blood stream is dramatically increased by attaching polyethylene glycol (PEG) units to the bilayer, known as long circulating (Stealth) liposomes.Physical methods such as iontophoresis, ultrasound, and tape-stripping can further assist the delivery of drugs encapsulated in liposomes. Recent breakthroughs with liposomes are beneficial to topically applied permeants, especially for dermatological medications, cosmetic ingredients, and protein/peptide macromolecules. The current review emphasizes the potential of various novel drug delivery strategies like liposomes, niosomes, aspasomes, microsponges, microemulsions, hydrogels proniosome gel formulations, and solid lipid nanoparticles in optimizing and enhancing the topical delivery of antiacne agents. it may be concluded from the study that complex lipid molecules, transfersomes, can increase the transdermal flux, prolong the release, and improve the site specificity of bioactive molecules.
B)PHYSICAL MEANS: 1. Phonosoresis(Sonophoresis): It is defined as the movement of drugs through intact skin & underlying soft tissues under the influence of an ultrasonic perturbation. It is safe technique for enhancing drug administration & is effective in clinical applications when with a proper frequency, power level, and duration. It increases drug permeation through the skin by disordering the structured lipids in the stratum corneum. Applications of low-frequency (20 KHz) ultrasound enhances transdermal transport of high-molecular weight proteins. Ultrasound based on hypothesis that if cavitation plays an important role in ultrasound-facilitated skin permeation, & since the cavitation threshold (i.e., the minimal ultrasound intensity required to cause cavitation) increases rapidly with an increase of ultrasound frequency lower frequency would cause more cavitation and hence, higher skin Permeation of a drug. Many conventional sonophoresis devices have been developed and they are categorized into basic types, namely the disk-type and the horntype.Ultrasonic energy delivered from devices is being used to enhance therapeutic efficacy in the treatment of local conditions by a process of phonosoresis and sonosoresis. Current research is applied on synergistic or additive effect. In addition, a sample of interstitial fluid or its components may be extracted through permeabilized skin for diagnostic applications. 2. Iontophoresis There has been a growing awareness in recent years of potential therapeutic importance of achieving true controlled drug delivery where the rate of drug output may be modulated in a precisely controlled manner. Transdermal drug delivery has usefulness in achieving the controlled delivery of pharmaceuticals, which are relatively small in molecular size and rather lipophilic in nature, however, these systems are rather limited in their capability of achieving the transdermal systemic delivery of peptides, proteins and drugs which is often charged and highly hydrophilic in nature. In order to deliver an ionic drug, peptide/protein molecule through transdermal delivery to attain a systemic effect, and chemical and/or physical methods is required to enhance the rate of penetration of therapeutic agent through the main diffusion barrier. The intophoratic technique is highly desirable to improve the transdermal delivery of peptide and proteins using a lower current intensity with a short time period. The idea of applying electric current to increase the penetration of electrically charged drugs into surface tissues was probably organized by Veratti in 1947. Leduc did the first well-documented experiments at the beginning of the 20th century. Leduc demonstrated the introduction of strychnine and cyanide ions into the rabbits when the correct polarities were applied. By the process of electromigration and electro-osmosis, iontophoresis increases the permeation of charged and neutral compounds, and offers the option for programmed drug delivery. Interest in this field of research has led to the successful delivery of both low (lidocaine) and high molecular drugs, such as peptides (e.g., luteinising hormone releasing hormone, nafarelin and insulin). Combinations of iontophoresis with chemical enhancers, electroporation and sonophoresis have been tested in order to further increase transdermal drug permeation and decrease possible side effects. In addition, rapid progress in the fields of microelectronics, nanotechnology and miniaturisation of devices is leading the way to more sophisticated iontophoretic devices, allowing improved designs with better control of drug delivery.
3.Electroporation It is a phenomenon in which the membrane of a cell exposed to high-intensity electric field pulses(up to several hundred volts for micro- or milliseconds) can be temporarily, thus becoming highly permeable to exogenous molecules in the surrounding media. A recent report provide a theoretical analysis according to which ,charged molecules were considered transporting through existing shunt routes of the skin at transdermal voltage <100 v. when transdermal voltage was greater than 100v, the transcorneocyte pathway was also accessible to charged molecules as lipid bilayers were electroporated.Synergistic effect was shown by ultrasound and electric field than positive of electric field only. Research is doing for effective, safe, cost-effective, as well as powerfully versatile (e.g., microchip controlled for complex drug delivery patterns).
C) CHEMICAL MEANS: Carbopol polymers are polymers of acrylic acid cross-linked with polyalkenyl ethers or divinyl glycol. They are produced from primary polymer particles of about 0.2 to 6.0 micron average diameter. The flocculated agglomerates cannot be broken into the ultimate particles when produced. Each particle can be viewed as a network structure of polymer chains interconnected via cross-linking. Carbomers were first prepared and patented in 1957. Since then, a number of extended release tablet formulations, which involve carbomer matrices, have been patented. Carbomers readily absorb water, get hydrated and swell. In addition to its hydrophilic nature, its cross-linked structure and its essentially insolubility in water makes Carbopol a potential candidate for use in controlled release drug delivery system. Carbopol polymers are manufactured by cross-linking process. Depending upon the degree of cross-linking and manufacturing conditions, various grades of Carbopol are available. Each grade is having its significance for its usefulness in pharmaceutical dosage forms Polymers produced in co solvent (a cyclohexane / ethyl acetate mixture) have a bulk density of 176 kg/m3 (11 lbs/ft3). Polymers produced in ethyl acetate have ash content (as potassium sulfate) of 1-3% on average. Conclusion: Semisolids constitute a significant proportion of pharmaceutical dosage forms. It has their peculiar theological behavior; semisolids can adhere to the application surface for sufficiently long periods before they are washed off. The novel approaches discussed were applicable for transdermal delivery of pharmaceuticals.