Pastes and Gels Notes

Pastes and Gels

Pastes

• Pastes are semisolid dosage forms containing a high percentage (often up to 50%) of finely dispersed solids within an ointment base.
• Uses:
  • Treatment of oozing lesions (absorb secretions).
  • Limit the area of treatment by acting as an absorbent and physical dam (do not spread over healthy skin).
  • Toothpastes.
• Advantages:
  • Heavy consistency (do not flow at body temperature).
  • Adhere to the skin and serve as protective coatings (porous rather than occlusive).

Preparation of Pastes

• Fusion method:
  • Melt all bases & wax with continuous stirring.
  • Add powdered ingredients.
  • Continuous and constant stirring until cool.
• Fusion and trituration method:
  • Melt the base.
  • Take powder (drug) and triturate with melted base (concentrate).
  • Triturate (mix) the concentrate with the remaining base (heat may be used to facilitate mixing).

Bases Used for Pastes

• Hydrocarbon base:
  • Soft paraffin and liquid paraffin.
• Water miscible base:
  • Emulsifying ointment.
  • Plasticized hydrocarbon (PEG + hydrocarbons).
• Water soluble bases:
  • PEG bases.

Types of Pastes

• Single-phase aqueous paste
  • Aqueous gel
  • Triamcinolone acetonide dental paste, USP
• Fatty paste
  • Hydrocarbon base
  • Zinc oxide paste, USP

Triamcinolone Acetonide Dental Paste (0.1%), USP Ingredients

• Gelling agent: Gelatin, Pectin, Carboxymethylcellulose sodium, Plasticized hydrocarbon gel (PEG and mineral oil).
• Thickening agent: Gelling agent B, Thickening agent ABC, Aqueous base D.
• Other excipients: vanilla and cream flavors. Pectin may also provide the sustained release of the drug at the site of application
• The Plasticized Hydrocarbon gel forms a soft, glossy base

Triple Paste Medicated Ointment (Zinc Oxide 12.8%), USP Ingredients

• Hydrocarbon base: White petrolatum, Corn starch, Anhydrous lanolin, Stearyl alcohol, Beeswax, Cholesterol
• Binder: Binder B
• Emulsion stabilizer: Emulsion stabilizer D
• Emulsifying agent: Emulsifying agent F
  *Other excipients: glycerin, oat kernel extract
  *Why are there no preservatives in this formulation?

Other Commonly Used Excipients in Pastes

• Additional/alternative hydrophobic solvents:
  • Liquid silicone (Polydimethylsiloxane) – water-repellent.
  • Vegetable oils (canola oil, sunflower oil, corn oil, soybean oil) – increase emollient properties.
  • Organic esters (isopropyl myristate) – enhances drug dissolution within the base (solubilizer).
• Preservatives (for pastes with water):
  • Parabens, benzoic acid and its salts, phenolics, etc.
• Antioxidants:
  • Lipophilic antioxidants (BHA, BHT).
  • Hydrophilic antioxidants (sodium sulfite/metabisulfite).

Difference Between Pastes and Ointments

• Pastes are semisolid dosage forms that contain a large proportion of solid components. They differ from ointments in their consistency, as they contain larger amounts of solids.

Gels

• Gels are colloids that contain small inorganic particles (two-phase) or large organic molecules (single phase) dispersed within a continuous liquid vehicle.
• The liquid medium is viscous enough to behave as a solid.
• Following application, the liquid evaporates, leaving the drug entrapped in a thin film of gel matrix covering the skin.

Gel Particle Movement

The movement of the particles in gels is restricted due to the 3D network and colloidal nature of the particles.

Classification of Gels

Gels are classified depending on the colloidal particle or the dispersion medium:

• Nature of the particle:
  • Inorganic gels.
  • Organic gels.
• Nature of the solvent:
  • Hydrogels (polar/aqueous).
  • Organogels (nonpolar/lipids).
• Natural polymers
• Semisynthetic
• Synthetic
• Lecithin based
• Fatty acids based
• Sorbitan ester based

Inorganic and Organic Gels

• Inorganic gels: Two-phase systems (inorganic particles dispersed throughout the continuous aqueous medium):
  • Aluminum hydroxide gel, USP
  • Bentonite magma, NF
• Organic gels: Single-phase systems (macromolecules distributed in a way that no apparent boundaries exist between particles and gel):
  • Contain gelling agents (natural or synthetic polymers), for example: polyacrylic acid polymers (Carbomer, Carbopol® 980), and tragacanth.

Characteristics of Gels: Structure

• Interlinking network of the gelling agent results in rigidity, which depends on the type of:
  • Dispersed particles (aggregates vs single macromolecules).
  • Forces between the linkages.
• Bentonite or kaolin (clays) forms a lamellar structure that can be extensively hydrated.

Adapalene® 0.1 % Topical Aqueous Gel Ingredients

• Gelling agent: Carbopol 980
• Chelating agent/stabilizer: EDTA sodium
• Preservative: Methylparaben
• Surfactant: Poloxamer 124
• Co-solvent: Propylene glycol
• Solvent: Purified water
• pH adjustment: Sodium hydroxide, Hydrochloric acid
• Carbopol 980 is a crosslinked polyacrylic acid
• Poloxamer 124 (Polyethylene-Polypropylene Glycol)

Hydrogels

• Water-swollen structures composed of mainly hydrophilic polymers that prevent water leaking out.
• Hydrophilic polymers are insoluble due to the presence of chemical crosslinks (covalent or ionic bonds) and physical crosslinks, including:
  • Entanglements
  • Crystallites
  • van der Waals interactions
  • $\pi–\pi$-stackings
  • Hydrogen bonds

Classification of Gelling Agents for Hydrogels

Organogels

• Contain organic (non-polar) solvents:
  • hexane
  • isopropyl myristate
  • sunflower oil, corn oil
• The gelation process involves the self-assembly of low-molecular-weight gelators (LMWGs) to give polymer-like fibers:
  • acrylic polymers
  • lecithin
  • polyethylene

Fenistil Gel (1 mg/g Dimetindene Maleate) Ingredients

• Gelling agent: Carbomer
• Chelating agent/stabilizer: EDTA sodium
• Preservative: Benzalkonium chloride
• Co-solvent: Propylene glycol
• Solvent: Purified water
• pH adjustment: Sodium hydroxide
  Is this a hydrogel or an organogel? Why?

Characteristics of Gels: Swelling or Imbibition

• An increase in volume due to liquid (solvent) taken up by the gelling agent.
• Gel-gel interactions are replaced by the gel-solvent interactions.

Characteristics of Gels: Syneresis or Weeping

• Opposite of swelling/imbibition.
• Many gels often contract spontaneously on standing and exude some fluid medium.
• Syneresis becomes more obvious as the concentration of the gelling agent increases.
• The process occurs in both organic and inorganic gels.

Characteristics of Gels: Thixotropy

• Due to their organized structures, some gels and magmas may be thixotropic.
• When agitated, they become liquids but form semisolids after standing for a period of time.
• Viscosity decreases with increased shear stress.
• Exhibit pseudoplastic non-Newtonian flow behavior, that is, they return to a gel state almost instantly.
• Therefore, shake before use to ensure homogeneity.

Smart Polymer Hydrogels

• Smart polymer hydrogels show significant changes in their properties (hydrophilicity, swelling ability, physical properties, molecular permeability) in response to external stimuli.
• Designing efficient drug delivery systems for systemic use (e.g. Jelmyto ®, containing mitomycin, consists of a smart hydrogel which transforms from a chilled liquid at instillation into a gel at body temperature, enabling the formulation to conform to the complex anatomy of the renal pelvis).

Xerogels

• Dry gels in which the vehicle has been removed, leaving a solid polymer network from which a drug can be released at a controlled rate.
• Xerogels have a high porosity (15 – 50%) and a very large surface area (150-900 m2/g).
• Examples:
  • Dry gelatin
  • Silk fibroin
  • Polystyrene
  • Tragacanth ribbons

Factors to Consider and Patient Counseling Points

• Always consider the effect of the vehicle. An occlusive vehicle enhances penetration of the active ingredient. The vehicle itself may have a cooling, drying, emollient, or protective action. It can also cause side effects.
• Match the type of preparation with the type of lesions and with the site of application.
• Clean (and dry) the affected area before applying the drug. If the skin is very dry and flaking, apply the medication while the skin is still damp.
• The patient should be instructed/trained as to the proper amount of topical agent that is to be used, to ensure the correct dose.
• Wash hands before and after use (using gloves may be recommended).
• An occlusive dressing, such as a bandage, should not be used unless needed to protect the area from excessive contact or contamination.
• Greasy ointments can stain clothing.
• Discuss the effect of applying moisturizers on skin absorption. Explain the order of administration in case of multiple formulations.