Advances in the formulation of semisolid dosage forms

The formulation of a suitable semisolid dosage form involves the selection of an appropriate drug carrier system, with a special emphasis on the drug’s physicochemical properties and required therapeutic application. Drug delivery by means of semisolid dosage forms has seen new challenges in the past few years in terms of altered drug-release profiles as well as the enhanced stability of active p dosage forms has seen new challenges harmaceutical ingredients (APIs).

 Systemic drug delivery: The skin’s large surface area1.73 m², facilitates its use as a potential site for the application of topical dosage forms .With this method, not only can some therapeutically active agents be delivered transdermally with ease, but first-pass gut and hepatic metabolism is avoided, constant drug levels in the bloodstream are maintained for longer periods of time, potential side effects are decreased, bioavailability is improved, the dosage is smaller, patient compliance is increased and drug termination in problematic cases is facilitated as compared with other routes of drug administration is improved, the dosage is smaller, patient compliance is increased stration Semisolid and drug termination in problematic cases is facilitated dosage forms have proven to be ideal carriers for this purpose and several novel developments in their formulation technologies have emerged in recent years. In addition to the use of penetration enhancers alone, their combination with cosolvents that deliver a drug solubilized form has led to the achievement of higher drug permeability.

 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 N-methylpyrrolidone 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 vehicle–antinucleant 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 vehicle–antinucleant polymer system Enhanced permeation of sodium nonivamide acetate (an antinociceptive agent) was observed with ethanol–buffer 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 membrane-like 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.