Isotropic formulations

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Isotropic formulations are thermodynamically stable microemulsions possessing lyotropic liquid crystal properties. [1] They inhabit a state of matter and physical behaviour somewhere between conventional liquids and that of solid crystals. [2] Isotropic formulations are amphiphillic, exhibiting selective synchronicity with both the water and lipid phases of the substrate to which they are applied. [3] Most recently, isotropic formulations have been used extensively in dermatology for drug delivery. [4]

Uses

While it is well established that the skin provides an ideal site for the administration of local and systemic drugs, it presents a formidable barrier to the permeation of most substances. [5] Isotropic formulations have been used to deliver drugs locally and systemically via the skin appendages, intercellular and transcellular routes. [6]

Related Research Articles

In physics and geometry, isotropy is uniformity in all orientations. Precise definitions depend on the subject area. Exceptions, or inequalities, are frequently indicated by the prefix a- or an-, hence anisotropy. Anisotropy is also used to describe situations where properties vary systematically, dependent on direction. Isotropic radiation has the same intensity regardless of the direction of measurement, and an isotropic field exerts the same action regardless of how the test particle is oriented.

In physical chemistry, supersaturation occurs with a solution when the concentration of a solute exceeds the concentration specified by the value of solubility at equilibrium. Most commonly the term is applied to a solution of a solid in a liquid. A supersaturated solution is in a metastable state; it may be brought to equilibrium by forcing the excess of solute to separate from the solution. The term can also be applied to a mixture of gases.

<span class="mw-page-title-main">Lipid bilayer</span> Membrane of two layers of lipid molecules

The lipid bilayer is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many viruses are made of a lipid bilayer, as are the nuclear membrane surrounding the cell nucleus, and membranes of the membrane-bound organelles in the cell. The lipid bilayer is the barrier that keeps ions, proteins and other molecules where they are needed and prevents them from diffusing into areas where they should not be. Lipid bilayers are ideally suited to this role, even though they are only a few nanometers in width, because they are impermeable to most water-soluble (hydrophilic) molecules. Bilayers are particularly impermeable to ions, which allows cells to regulate salt concentrations and pH by transporting ions across their membranes using proteins called ion pumps.

<span class="mw-page-title-main">Route of administration</span> Path by which a drug, fluid, poison, or other substance is taken into the body

A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body.

<span class="mw-page-title-main">Liposome</span> Composite structures made of phospholipids and may contain small amounts of other molecules

A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug delivery vehicles for administration of pharmaceutical drugs and nutrients, such as lipid nanoparticles in mRNA vaccines, and DNA vaccines. Liposomes can be prepared by disrupting biological membranes.

<span class="mw-page-title-main">Amphotericin B</span> Antifungal and antiparasitaric Chemical compound

Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis. For certain infections it is given with flucytosine. It is typically given intravenously.

<span class="mw-page-title-main">Topical medication</span> Medication applied to body surfaces

A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes including creams, foams, gels, lotions, and ointments. Many topical medications are epicutaneous, meaning that they are applied directly to the skin. Topical medications may also be inhalational, such as asthma medications, or applied to the surface of tissues other than the skin, such as eye drops applied to the conjunctiva, or ear drops placed in the ear, or medications applied to the surface of a tooth. The word topical derives from Greek τοπικόςtopikos, "of a place".

In physics and engineering, permeation is the penetration of a permeate through a solid. It is directly related to the concentration gradient of the permeate, a material's intrinsic permeability, and the materials' mass diffusivity. Permeation is modeled by equations such as Fick's laws of diffusion, and can be measured using tools such as a minipermeameter.

<span class="mw-page-title-main">Drug delivery</span> Methods for delivering drugs to target sites

Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to drug preparation, route of administration, site-specific targeting, metabolism, and toxicity are used to optimize efficacy and safety, and to improve patient convenience and compliance. Drug delivery is aimed at altering a drug's pharmacokinetics and specificity by formulating it with different excipients, drug carriers, and medical devices. There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. Some research has also been focused on improving safety for the person administering the medication. For example, several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury.

Pharmaceutical formulation, in pharmaceutics, is the process in which different chemical substances, including the active drug, are combined to produce a final medicinal product. The word formulation is often used in a way that includes dosage form.

<span class="mw-page-title-main">Transdermal</span>

Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery. The drug is administered in the form of a patch or ointment that delivers the drug into the circulation for systemic effect.

<span class="mw-page-title-main">Solid lipid nanoparticle</span> Novel drug delivery system

Lipid nanoparticles (LNPs) are nanoparticles composed of lipids. They are a novel pharmaceutical drug delivery system, and a novel pharmaceutical formulation. LNPs as a drug delivery vehicle were first approved in 2018 for the siRNA drug Onpattro. LNPs became more widely known in late 2020, as some COVID-19 vaccines that use RNA vaccine technology coat the fragile mRNA strands with PEGylated lipid nanoparticles as their delivery vehicle.

Microbubbles (MBs) are bubbles smaller than one hundredth of a millimetre in diameter, but larger than one micrometre. They have widespread application in industry, life science, and medicine. The composition of the bubble shell and filling material determine important design features such as buoyancy, crush strength, thermal conductivity, and acoustic properties.

DDAIP is a pharmaceutical ingredient added to topical products to increase penetration through the skin. Chemically, DDAIP is an ester of N,N-dimethylalanine and dodecanol, although as of now the structural formula shows an ester with decanol (C10) instead. DDAIP is typically formulated as its hydrochloride salt (DDAIP.HCl). This salt is a white crystalline solid with a melting range of 88-93 °C and is an amphiphilic molecule with a pKa of 4.87 that is soluble in water up to about 40% w/v. DDAIP is proprietary to NexMed USA, a subsidiary of Apricus Biosciences.

Buccal administration is a topical route of administration by which drugs held or applied in the buccal area diffuse through the oral mucosa and enter directly into the bloodstream. Buccal administration may provide better bioavailability of some drugs and a more rapid onset of action compared to oral administration because the medication does not pass through the digestive system and thereby avoids first pass metabolism.

Nanoparticles for drug delivery to the brain is a method for transporting drug molecules across the blood–brain barrier (BBB) using nanoparticles. These drugs cross the BBB and deliver pharmaceuticals to the brain for therapeutic treatment of neurological disorders. These disorders include Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and brain tumors. Part of the difficulty in finding cures for these central nervous system (CNS) disorders is that there is yet no truly efficient delivery method for drugs to cross the BBB. Antibiotics, antineoplastic agents, and a variety of CNS-active drugs, especially neuropeptides, are a few examples of molecules that cannot pass the BBB alone. With the aid of nanoparticle delivery systems, however, studies have shown that some drugs can now cross the BBB, and even exhibit lower toxicity and decrease adverse effects throughout the body. Toxicity is an important concept for pharmacology because high toxicity levels in the body could be detrimental to the patient by affecting other organs and disrupting their function. Further, the BBB is not the only physiological barrier for drug delivery to the brain. Other biological factors influence how drugs are transported throughout the body and how they target specific locations for action. Some of these pathophysiological factors include blood flow alterations, edema and increased intracranial pressure, metabolic perturbations, and altered gene expression and protein synthesis. Though there exist many obstacles that make developing a robust delivery system difficult, nanoparticles provide a promising mechanism for drug transport to the CNS.

<span class="mw-page-title-main">Ethosome</span>

Ethosomes are phospholipid nanovesicles used for dermal and transdermal delivery of molecules. Ethosomes were developed by Touitou et al.,1997, as additional novel lipid carriers composed of ethanol, phospholipids, and water. They are reported to improve the skin delivery of various drugs. Ethanol is an efficient permeation enhancer that is believed to act by affecting the intercellular region of the stratum corneum. Ethosomes are soft malleable vesicles composed mainly of phospholipids, ethanol, and water. These soft vesicles represent novel vesicles carriers for enhanced delivery through the skin. The size of the ethosomes vesicles can be modulated from tens of nanometers to microns.

<span class="mw-page-title-main">Topical cream formulation</span>

Topical cream formulation is an emulsion semisolid dosage form that is used for skin external application. Most of the topical cream formulations contain more than 20 per cent of water and volatiles and/or less than 50 per cent of hydrocarbons, waxes, or polyethylene glycols as the vehicle for external skin application. In a topical cream formulation, ingredients are dissolved or dispersed in either a water-in-oil (W/O) emulsion or an oil-in-water (O/W) emulsion. The topical cream formulation has a higher content of oily substance than gel, but a lower content of oily ingredient than ointment. Therefore, the viscosity of topical cream formulation lies between gel and ointment. The pharmacological effect of the topical cream formulation is confined to the skin surface or within the skin. Topical cream formulation penetrates through the skin by transcellular route, intercellular route, or trans-appendageal route. Topical cream formulation is used for a wide range of diseases and conditions, including atopic dermatitis (eczema), psoriasis, skin infection, acne, and wart. Excipients found in a topical cream formulation include thickeners, emulsifying agents, preservatives, antioxidants, and buffer agents. Steps required to manufacture a topical cream formulation include excipient dissolution, phase mixing, introduction of active substances, and homogenization of the product mixture.

Topical drug delivery (TDD) is a route of drug administration that allows the topical formulation to be delivered across the skin upon application, hence producing a localized effect to treat skin disorders like eczema. The formulation of topical drugs can be classified into corticosteroids, antibiotics, antiseptics, and anti-fungal. The mechanism of topical delivery includes the diffusion and metabolism of drugs in the skin. Historically, topical route was the first route of medication used to deliver drugs in humans in ancient Egyptian and Babylonian in 3000 BCE. In these ancient cities, topical medications like ointments and potions were used on the skin. The delivery of topical drugs needs to pass through multiple skin layers and undergo pharmacokinetics, hence factor like dermal diseases minimize the bioavailability of the topical drugs. The wide use of topical drugs leads to the advancement in topical drug delivery. These advancements are used to enhance the delivery of topical medications to the skin by using chemical and physical agents. For chemical agents, carriers like liposomes and nanotechnologies are used to enhance the absorption of topical drugs. On the other hand, physical agents, like micro-needles is other approach for enhancement ofabsorption. Besides using carriers, other factors such as pH, lipophilicity, and drug molecule size govern the effectiveness of topical formulation.

Penetration enhancers are chemical compounds that can facilitate the penetration of active pharmaceutical ingredients (API) into or through the poorly permeable biological membranes. These compounds are used in some pharmaceutical formulations to enhance the penetration of APIs in transdermal drug delivery and transmucosal drug delivery. They typically penetrate into the biological membranes and reversibly decrease their barrier properties.

References

  1. Leslie FM. “Contiuum Theory for Nematic Liquid Crystals Continuum Mechanics and Thermodynamics.” 1992. 4 (3): 167
  2. Ghosh SK. “A Model for the Orientational Order in Liquid Crystals.” Il Nuovo Cimento D 1984 4 (3): 229
  3. Chen C, Han D, Cai C, Tang X. “An Overview of Liposome Lyopholisation and its Future Potential Journal of Controlled Release.” 2010; 142:299-311
  4. Gregoriadis G. “Lipsomes in Drug Delivery.” Harwood Academic Publishers, 1993;
  5. Landman L. “The Epidermal Permeability Barrier.” Anat Embryol (Berl) 1988; 178:1-13
  6. Harada K. Murakami T. Yata N et al. “Role of Intercellular Lipids in Stratum Corneum in the Percutaneous Permeation of Drugs.” J Invest Dermatol 1992; 9 99: 278-282