Topical Drug Delivery PDF

3.2 Topical Drug Delivery Dosage forms are classified as liquids, semisolids, and solids. Semisolids Ointments are semisolid preparations intended for external application to the skin or mucus membranes. ○ They usually, but not always, contain a medicinal substan...

3.2 Topical Drug Delivery Dosage forms are classified as liquids, semisolids, and solids. Semisolids Ointments are semisolid preparations intended for external application to the skin or mucus membranes. ○ They usually, but not always, contain a medicinal substance. ○ Ointments are classified based on their interaction with water: Hydrocarbon (Oleaginous) bases are very greasy and insoluble in water. They are anhydrous and do not absorb water. Examples include: White petrolatum USP , a highly refined mixture of saturated hydrocarbons. The most well-known brand is Vaseline. White ointment USP , similar to white petrolatum, but with added wax (typically beeswax) for stiffness and smoothness. Therapeutic properties: Form an adherent, continuous, greasy, and water-repellent film. Good occlusiveness (block transepidermal water loss). Emollient effect (softens the skin). Enhance drug permeation. Prolonged contact with the skin, increasing drug residence time. Good protection. Patient acceptance: Greasy and may feel unpleasant. Not water washable. Can stain clothing. Absorption bases are greasy, anhydrous, and can absorb water due to the presence of surfactants. They typically form water-in-oil emulsions when water is incorporated. Examples include:  Lanolin , a natural absorption base extracted from sheep wool. Hydrophilic petrolatum USP , commercially known as Aquaphor. Contains petrolatum, mineral oil, mineral wax, and wool wax alcohol (the main surfactant). Therapeutic properties: Form an adherent, greasy film. Moderately occlusive. Moderately good emollient and protective properties. Remain on the skin for a prolonged period. Can enhance drug delivery. Patient acceptance: Greasy and not water washable. Emulsion bases come in two types: Water-in-oil, where oil is the external phase. They absorb less water than anhydrous absorption bases because they already contain water. Examples include: Hydrous lanolin , anhydrous lanolin with added water (20-30%). Eucerin , similar to Aquaphor but with added water and preservatives. Therapeutic properties: Somewhat occlusive, but less so than anhydrous or hydrocarbon bases.  Moderately good emollient and protective properties. Less ability to block transepidermal water loss. Patient acceptance: Somewhat greasy, but not as greasy as anhydrous absorption bases. Not easily water washable, but easier to wash off than Vaseline. More pleasant to apply than anhydrous absorption bases. Oil-in-water , where water is the external phase. They can absorb varying amounts of water and can be transformed into lotions by adding and mixing water. Water washable. Often considered the classic creams. Examples include: Hydrophilic ointment USP , commercially known as vanishing cream base. Therapeutic properties: Upon application, the water evaporates, leaving a thin, transparent film. High concentration of drug film enhances drug delivery. Less occlusive than water-in-oil emulsion bases and do not block transepidermal water loss. Less protective and emollient. Patient acceptance: Non-greasy and easy to apply. Highly acceptable. Water-soluble bases are uncommon and made of polyethylene glycols (PEGs). They feel greasy but are water soluble and non-occlusive. Examples include: Mupirocin ointment , formerly known as Bactroban, contains PEG 400 and a higher molecular weight PEG. Patient acceptance:  Acceptable. Water washable and greaseless. Can be irritating to wounds. Pastes are ointments containing a high percentage (20-50%) of fine powder. ○ The base is usually petrolatum. ○ Examples of powders used in pastes: Zinc oxide. Talc. Starch. Bentonite. ○ Examples include: Boudreaux's Butt Paste , a skin protectant used for diaper rash. ○ Therapeutic properties: Form a thick, protective film upon application. Less greasy and occlusive than the corresponding base without powder. Absorptive. More protective and stiff. ○ Application: Applied as a thick film, unlike other topical dosage forms. Liquids Lotions are fluid emulsions or suspensions intended for external application. ○ The continuous phase is aqueous. ○ Examples include: Calamine lotion. Clotrimazole lotion. Selenium sulfide lotion. Cetaphil , an oil-in-water emulsion marketed as a lipid-free lotion. A good moisturizing lotion and general-purpose lotion vehicle. ○ Therapeutic properties: Upon application, the continuous phase evaporates, leaving a thin film of powder or liquid. Non-occlusive. Evaporation cools and soothes the skin. Fluidity allows for quick application over large areas and facilitates application to challenging areas like hairy or intertriginous areas. ○ Patient acceptance: Highly acceptable.  Water washable, non-greasy, and easy to apply. ○ Stability: Similar to oral suspensions and emulsions, they can experience physical instability (separation, settling), chemical instability, and microbiological instability. Topical solutions are generally aqueous vehicles, sometimes containing alcohol. ○ Examples include: Burrow's solution. Dakin's solution (diluted sodium hypochlorite). Tinctures use alcohol or hydroalcoholic vehicles. ○ Example: Iodine tincture. Gels: An In-Depth Study Guide Gels are a significant category of semi-solid topical dosage forms. Here's a detailed examination of gels based on the provided source: Definition: Gels are defined as semi-solid systems where a liquid phase is confined within an interconnected polymeric matrix. This matrix can originate from natural or synthetic gums, with the term "gum" in pharmacy often signifying a polysaccharide. Composition: ○ Liquid Phase: Typically, the liquid phase is water. However, it can also contain miscible co-solvents like alcohols such as ethanol or isopropyl alcohol. ○ Drug: The drug is usually either suspended or dissolved within this liquid phase. ○ Gelling Polymers: The polymers responsible for gel formation are frequently the same as those employed as suspending agents in oral suspensions, only in higher concentrations to achieve the desired gel-like consistency. Examples include: Carbomer Tragacanth Alginic Acid Cellulose Derivatives (e.g., methylcellulose, carboxymethylcellulose) Characteristics: Most gels are designed to be both water-soluble and water-absorbing. Examples: ○ Hand Sanitizer Gel (classic example) ○ Benzoyl Peroxide Gel (acne treatment) ○ NSAID Gels (e.g., Voltaren gel for joint pain) ○ Testosterone Gel  ○ Benzomycin Gel (acne treatment) ○ Clindamycin Phosphate Gel (acne treatment) Patient Acceptance and Therapeutic Properties: ○ Application: Upon applying a gel, the solvent evaporates, leaving behind a porous matrix film. This film allows for drug diffusion. ○ Drug Delivery: This porous matrix is highly efficient in releasing the drug, making gels advantageous for drug delivery. ○ Penetration Enhancement: Solvents like ethanol can further enhance drug penetration into the skin. ○ Potency: Due to efficient drug release and potential penetration enhancement, gels often exhibit greater potency compared to other dosage forms with the same drug concentration. Additional Notes: The source emphasizes that not all gelling polymers are polysaccharides. The example provided, hand sanitizer gel, uses a carbomer, which is not a polysaccharide. While the classic gel is clear, many gels, such as benzoyl peroxide gel, are not. The source also points out that gels are versatile and can be formulated to deliver various types of drugs. Collodions are liquid preparations of pyroxylin (a cotton derivative) dissolved in a solvent containing alcohol, ether, and acetone, with or without added drug. ○ Upon application, the solvent evaporates, leaving an occlusive, film-like residue of pyroxylin that can seal small wounds and protect surrounding tissue. ○ Example: Wart treatment. Castor oil can be added as a plasticizer to soften the pyroxylin and ensure it stays in place. Other Topical Dosage Forms  Aerosols are blends of drug and propellant, functioning as delivery systems for solutions, suspensions, powders, and emulsions. ○ They allow for spray application without rubbing, making them useful for areas where rubbing would be irritating (e.g., sunburns). ○ Examples include: Antifungal spray powders. Sunburn products like Solarcaine. Plasters are a solid or semisolid adhesive mass spread on a backing material, intended for prolonged external application. ○ ○ They are similar to patches but can be cut to the shape of the area being treated. ○ Example: Salicylic acid plaster (e.g., Mediplast) used for plantar warts and calluses. Wet dressings are aqueous solutions applied as a dressing (e.g., gauze, linens) soaked in the solution. ○ ​ ○ The solutions are typically astringents (stop bleeding or secretions by precipitating proteins) or antiseptic agents. ○ Benefits: Cleanse wounds of exudates. Help maintain drainage of infected wounds. Promote wound healing. Repeated application and removal can dry the skin and remove exudates and secretions. ○ Example: Aluminum acetate. Foams are gas-propelled liquids or solids administered as aerosols, similar to shaving cream in consistency.  ○ ○ Benefits: Gentle and easy to spread without rubbing. Non-runny. ○ Drawback: Tends to break down quickly. Excipients in Topical Dosage Forms Antioxidants prevent rancidity in hydrocarbon-containing dosage forms. ○ Examples include: Butylated hydroxytoluene (BHT). Butylated hydroxyanisole (BHA). Vitamin E (alpha-tocopherol). Antimicrobial preservatives prevent microbial growth in water-containing dosage forms. ○ Examples include: Benzalkonium chloride. Parabens. Benzoic acid. Waxes increase stiffness and reduce tackiness in ointments and creams. ○ Examples include: Beeswax. Cetyl esters wax. Cetyl alcohol. Moisturizers hydrate the skin and are classified as: ○ Occlusive , which inhibit transepidermal water loss: Petrolatum is highly occlusive, reducing transepidermal water loss by about 99%. Aquaphor is also occlusive, though less so than petrolatum. Dimethicone and other silicones are non-oleaginous occlusive agents, often used in oil-free moisturizers.  ○ Humectants , which are hygroscopic and attract water to hydrate the skin: They are often added to creams and lotions to enhance moisturizing capacity. They can work within the skin, augmenting the skin's hygroscopic capacity, or on the skin surface, absorbing atmospheric moisture (dependent on humidity). At high humidity, they draw water from the atmosphere into the skin, but in arid environments, they can draw water from the skin, leading to a drying effect. Examples include: Propylene glycol. Glycerin. Sorbitol. Urea. Alpha hydroxy acids (AHAs, e.g., lactic acid). These agents can also function as penetration enhancers by hydrating the skin. Co-solvents enhance drug solubility and prevent precipitation as the dosage form dries. ○ Examples include: Propylene glycol is commonly used in creams to prevent drug precipitation and enhance permeation. Glycerin is a good co-solvent because it does not evaporate easily. Ethanol evaporates quickly but can enhance penetration. Practical Considerations for Topical Medications Application: ○ A thin film is usually sufficient, with the exception of diaper rash pastes. ○ The fingertip unit is a method for estimating dosage, representing the amount dispensed from a tube reaching from the fingertip to the first crease of the index finger (approximately 0.5 grams). ○ The rule of hand estimates the amount of product needed for a thin film application to both sides of the hand (one hand area) as one fingertip unit. General advice for application: ○ Cleanse and dry the area to be treated. ○ Apply shortly after bathing or showering when the stratum corneum is hydrated. ○ Apply moisturizers within 3 minutes of bathing or showering. ○ Cleanse hands before and after application. ○ Use gentle rubbing motions to apply creams and ointments, apply lotions as drops and massage lightly, and rub gels gently and completely. Precautions: ○ Avoid drug transfer to sensitive areas, such as the eyes, by cleansing hands. ○ Exercise caution when applying to thin-skinned areas (e.g., face, back of hands), as the thinner stratum corneum allows for greater drug penetration. ○ Intertriginous areas (where skin touches skin) are naturally occlusive, potentially increasing drug potency, so use caution. ○ Avoid applying medicated products to large areas, especially in children, as it can lead to increased drug penetration and systemic absorption.