Semisolid Dosage Forms

Semisolid Dosage Forms

• Semisolid dosage forms are materials that conform to their container at room temperature and distort easily under force.

Topical Dosage Forms

• Topical dosage forms deliver drugs into the skin to treat skin disorders
• They protect injured areas, permit skin healing, provide skin hydration, produce emollient effects and convey medication to the skin.

Transdermal Dosage Forms

• Transdermal dosage forms deliver drugs through the skin into general circulation for systemic effects.
• Examples include ointments, creams, gels, lotions, pastes, plasters, sticks, and glycerogelatins.

Factors Affecting Drug Penetration in Semisolids

• The volume of drug that penetrates the skin from semisolids is determined by:
• The amount of pressure applied and the vigor with which the semisolid is rubbed.
• The surface area covered; larger areas lead to greater drug absorption.
• The condition of the skin; hydration favors percutaneous absorption, and thin layers promote greater absorption.
• The base used.
• The use of occlusive dressings enhances penetration.
• The longer the medicated application remains in contact with the skin, the greater the total drug absorption.
• Heat can increase absorption through vasodilation.

Nitro-Bid Ointment

• 1 gram is approximately equivalent to 1 inch when squeezed from a tube.
• It's critical to be wary of the dose due to the product's potency.

Selection of a Base

• Considerations include whether the effect is topical or systemic, drug stability, desired release rate, the characteristic of the application surface and the need for occlusion or ease of removal.
• A prescriber may specify the base; if not, the selection is up to the compounder.

Oleaginous Bases (Hydrocarbon Bases/Ointment Bases)

• Advantages: Inexpensive, non-irritating, and provide good emollient and occlusive properties.
• Disadvantages: Poor patient acceptance due to a greasy nature, not easily removed with washing and cannot absorb water.
• Types: Yellow petrolatum (with impurities), white petrolatum (impurities removed), and white ointment (white petrolatum with beeswax).

Absorption Bases

• Anhydrous absorption bases: Hydrocarbon bases with emulsifiers that form water-in-oil emulsions when water or aqueous solution is added.
• Examples: Aquaphor (absorbs an equal volume of water i.e. 1:1 ratio), Lanolin.
• Water-in-oil emulsions: Absorption bases that already contain water.
• Advantages: Moderately protective, occlusive, emollient properties, do not wash off easily, allows for incorporating aqueous solutions into an oleaginous base and can absorb liquid.
• Disadvantages: Poor patient acceptance due to greasy nature, sticky texture, may be sensitizing (wool wax), and potential chemical stability issues in the presence of water.
• A base containing water has a BUD of 14 days.

Water-Removable Bases (Oil-in-Water Emulsions)

• Advantages: Non-greasy, can be removed from skin by washing, can absorb water or alcohol, and allow fluid dissipation from injured skin.
• Disadvantages: Less protective, emollient, and occlusive, chemical stability issues, subject to microbial growth, and may "dry out".

Water-Soluble Bases

• Advantages: Leave no oil residue, soluble in water, can absorb water and alcohol, and useful for incorporating solid substances.
• Disadvantages: Irritating, little to no emollient properties, compatibility issues with PEG-type bases, chemical stability problems, and subject to microbial growth.

Base Properties: Oleaginous vs. Absorption vs. Water-in-Oil

• Composition:
  • Oleaginous: Hydrophobic compounds.
  • Absorption: Hydrophobic compounds + w/o surfactants.
  • W/O: Hydrophobic compounds + w/o surfactants + water.
• Water content:
  • Oleaginous: Anhydrous.
  • Absorption: Anhydrous.
  • W/O: Moderate.
• Affinity for water:
  • Oleaginous: Low.
  • Absorption: Low.
  • W/O: Moderate.
• Spreadability:
  • Oleaginous: Difficult.
  • Absorption: Difficult.
  • W/O: Moderate.
• Washability:
  • Oleaginous: Not washable.
  • Absorption: Not washable.
  • W/O: Moderate.
• Greasiness:
  • Oleaginous: Greasy.
  • Absorption: Greasy.
  • W/O: Moderate.
• Drug Incorporation:
  • Oleaginous: Solids or oils.
  • Absorption: Solids, oils, small amounts of aqueous solutions.
  • W/O: solids or aqueous solutions.
• Levigating agent:
  • Oleaginous: Mineral oil.
  • Absorption: Mineral oil, low HLB surfactant.
  • W/O: Glycerin; high HLB surfactant. Occlusiveness:
  • Oleaginous: Yes.
  • Absorption: Yes.
  • W/O: No. Examples: Aquabase, Aquaphor, hydrophilic petrolatum.

Base Properties: Oil-in-Water vs. Water-Soluble vs. Hydrophilic Bases

• Composition:
  • Oil/Water: Hydrophobic compounds + water + o/w surfactant.
  • Water-Soluble: Polyethylene glycols (PEG).
  • Hydrophilic: Methylcellulose or carbomer dispersion.
• Water content:
  • Oil/Water: Hydrous.
  • Water-Soluble: Hydrous.
  • Hydrophilic: >95%.
• Affinity for water:
  • Oil/Water: High.
  • Water-Soluble: High.
  • Hydrophilic: High.
• Spreadability:
  • Oil/Water: Easy.
  • Water-Soluble: Easy.
  • Hydrophilic: Easy.
• Washability:
  • Oil/Water: Washable.
  • Water-Soluble: Washable.
  • Hydrophilic: Washable.
• Greasiness:
  • Oil/Water: Not greasy.
  • Water-Soluble: Not greasy.
  • Hydrophilic: Not greasy.
• Drug Incorporation:
  • Oil/Water: Solids and aqueous solutions.
  • Water-Soluble: Solids and aqueous solutions.
  • Hydrophilic: Solids and aqueous solutions.
• Levigating Agent:
  • Oil/Water: Glycerin; High HLB surfactant.
  • Water-Soluble: Glycerin, propylene glycol.
  • Hydrophilic: Glycerin, High HLB surfactant.
• Occlusiveness:
  • Oil/Water: No.
  • Water-Soluble: No.
  • Hydrophilic: No.

Compounding Approach

• Pre-formulation: Understand drug properties, focusing on solubility and stability.
• References: Use reference books, acceptable formulations with stability data, and commercial products as guides.
• Design Fundamentals: Consider bioavailability, stability, compliance, and marketing.

Dosage Form Fundamentals

• Active Pharmaceutical Ingredient (API): The active drug providing the therapeutic effect.
• Excipients: Support absorption, stability, or the manufacturing process of the API.
• Packaging: Protects dosage form integrity from stability issues and adverse effects.
• Administration Device: Necessary materials and equipment for drug administration.

Compounding Considerations

• Commonly compounded semisolids: Ointments, creams, lotions, and gels.
• Compounding considerations: Base selection, excipients, calculations and technique.

Excipients

• Stiffening agents: Waxes with high melting points used to enhance viscosity in oleaginous bases (e.g., chapsticks, medicated sticks).
• Emulsifying agents: Needed to combine immiscible liquids.
• Humectants: Decrease the evaporation rate of water.
• Preservatives: Needed if the product contains water.
• Absorption Enhancers: Facilitate drug absorption through the skin.

Ointments

• Semisolid preparations intended for external application to the skin or mucous membranes; may be medicated or not.
• Properties: Soften or melt at body temperature, spread easily, and should not be gritty.
• Use: Generally used on dry, scaly lesions due to emollient properties.
• Preparation Methods: Incorporation and Fusion.

Ointment Preparation: Incorporation

• Reduce particle size of solids or crystalline materials and levigate using mineral oil (for oil-based) or glycerin (for water-based).
• Incorporate the dispersion into the ointment base using geometric proportions with a spatula.

Ointment Preparation: Incorporation of Liquids

• Dissolve solids in a common solvent before adding to the base, considering the base's liquid capacity.
• Small aqueous solution amounts can be added to oleaginous ointments; hydrophilic bases accept them more readily; all bases have limits.
• Add an aqueous preparation to a hydrophobic base by first incorporating it into a minimal amount of hydrophilic base.

Ointment Preparation: Fusion

• Combine components by melting together, then cooling with constant stirring until congealed in a glass beaker or porcelain evaporating dish.
• Materials with higher melting points should be heated first, followed by those with lower melting points during cooling; liquids are added last.

Creams

• Semisolid preparations containing medicinal agents dissolved or dispersed in a W/O or O/W emulsion.
• Properties: Relatively soft, easy to spread and remove, can be either opaque, soft solids, or thick liquids and are generally applied to moist, weeping lesions.
• Creams do not have to be scrubbed of burns, which prevents additional trauma.

Cream Preparation: Incorporation

• Triturate the drug into a fine powder using a mortar and pestle, then remove it with a rubber spatula.
• Levigate the drug into the base in geometric proportions on an ointment slab using a metal spatula.

Cream Preparation: Fusion

• Separate the formula components into oil-soluble and water-soluble portions.
• Heat both phases to a temperature above the melting point of the highest melting component.
• Mix the phases by adding the aqueous phase to the oil phase.
• Add heat-stable, non-volatile APIs at the beginning or at the end when the mixture is almost congealed.

Gels

• Semisolid systems consisting of dispersions of small or large molecules in an aqueous liquid vehicle with a gelling agent.
• Examples: Androgel.
• Gelling agents: Synthetic (carbomers), cellulose derivatives (methylcellulose), or natural gums (tragacanth).
• Single-phase gels: Uniform distribution of gelling agent and liquid.
• Two-phase gels: Consist of floccules of distinct particles.
• Milk of Magnesia is an example of Magma.
• Preparation: Depends on the characteristics of the gelling agent and involves dispersing the API in the continuous phase.

Suppositories

• Solid dosage forms in which APIs are dispersed in a suitable base, molded for insertion into body orifices where they melt, soften, or dissolve, exerting local/systemic effects.
• Can be rectal, vaginal or urethral.
• Local Action: Base melts/softens/dissolves, distributing medications locally (e.g., for constipation relief, irritation, contraception, anti-infectives, or local anesthesia).
• Systemic Action: Absorption through mucous membranes (e.g., antiemetics, analgesics).

Suppository Advantages

• Alternative administration route, avoids oral/GI irritation, bypasses unpleasant tastes/smells, useful for nausea/vomiting, patients are unconscious, avoids first-pass effect and degradation, allows larger doses and circumvents upper GI tract diseases.

Suppository Bases

• Desirable properties: Remain solid (room temp), soften/melt/dissolve at body temp, chemically/physically stable, nonreactive/compatible, non-irritating, mix with water.

Suppository Base Categories

• Two categories: Oleaginous (Fatty) and Water-soluble.

Oleaginous (Fatty) Bases

• Most frequently used.
• Cocoa butter: Yellowish solid with a mild odor.
• Advantages: Non-irritating, excellent emollient, can be hand-molded, readily available.
• Disadvantages: Low melting point (requires controlled room temperature/refrigeration) and can exist in polymorphic forms (easily overheated, solidifies at lower mp).

Other Oleaginous Bases

• Hydrogenated vegetable oils (palm/palm kernel/coconut oils).
• Commercial products (Fattibase, Witepsol, Fattyblend) are easier to work with because they do not exhibit polymorphism.

Water-Soluble Bases

• Glycerinated gelatin: Soft, rubbery consistency; dissolves, but does not melt; slow to soften/mix and must be protected from atmospheric moisture.
• Polyethylene Glycol (PEG): Composed of various molecular weight PEG polymers; dissolves, but does not melt, available in numerous ranges of molecular weight and allows for slower medication release.
• Glycerinated gelatin and PEG: May be irritating and must be protected especially drugs prone to oxidation.

Suppository Preparation: Hand Molding

• Uses cocoa butter.
• Grate cocoa butter, add active ingredient, mix thoroughly, press together until re-solidified, shape into cylinder, cut to length and round for packaging.

Suppository Preparation: Fusion Molding

• Calibrate the mold.
• Melt sufficient suppository base and pour into molds, cool, and trim.
• Divide total weight by suppository number for average weight.

Suppository Preparation: Fusion Molding Details

• Mold Preparation: Ensure mold is clean and dry, lubricate with a substance opposite to the base's solubility (mineral oil for water-soluble, glycerin/propylene glycol for oil-soluble) and use minimal amounts to avoid misshapen suppositories.
• Base Preparation: The base should be melted using the least possible heat possible, generally using a porcelain dish over a water bath
• Active Drug Preparation: Triturate drug to a uniform size and levigate with a wetting agent of same property as base before incorporating.
• Mixing, Pouring, Cooling, Finishing: Mix drug into molten base with a stirring rod ensuring uniform distribution, pour quickly into mold and allow a slight excess of material, allow suppositories to set and then remove, package, and label.

Suppository Preparation: Cold Compression Molding

• Suitable for bases that can be formed into suppositories under pressure.
• The base is grated, mixed with the drug, and put into a cold compression mold.
• The amount of base required to fill each mold must be known or calculated.

Troches

• Troches or lozenges are various-shaped solid dosage forms, usually containing a medicinal agent and a flavoring substance, that are intended to be dissolved slowly in the oral cavity for localized or systemic effect.
• Advantages: Convenient, extends drug residence in the oral cavity for therapeutic effect.
• Disadvantage: Can be mistaken for candy.

Types of Troches

• Hard troches (lozenges, drops): Mixtures of sugar and other carbohydrates with a smooth surface texture and pleasant flavor that masks the drug taste, requires high temperature.
• Soft troches (pastilles): Mixtures of various PEGs, acacia, or similar ingredients.
• Chewable troches (gummies): Formulated with a gelatin and highly flavored.

Troche Preparation: Hard Troches

• Requires high temperature.
• Simple formulations contain drag, sugar, corn syrup, and water.
• Drug is dissolved in solution.
• Water is removed by boiling at 154–160 degrees; monitor temperature.
• Transfer amorphous sugar mass to mold.

Troche Preparation: Soft Troches

• Simple formulations contain drug, sugar, wax, and various PEG ingredients and binders, flavors and coloring agents may be included.
• Select desired base and calibrate.
• Perform all calculations and weigh all ingredients.
• Weigh ingredients.
• Lubricate troche mold.
• Levigate drug.
• Melt over evaporating dish over water bath while string with glass rod.
• Monitor temperature.
• Dispense in melt and ensure uniform distribution.
• Pour melt to mold.
• Allow melted troches to harden and place cover over product.
• Store and label properly.

Troche Preparation: Chewable Troches

• Gummies formulated with gelatin.
• Simple formulations contain drug, gelatin, glycerin, and water.
• Commercially prepared.
• Binders, favoring, and coloring agents.

Dosage form fundamentals: Excipients

• Adsorbents: Keep powders dry. Example: Magnesium oxide/carbonate.
• Antioxidants: Prevent oxidation Example: Ascorbic Acid
• Binders: Adhesive materials to hold powders together. Example: acacia, starch paste.
• Coatings: Prevent degradation due to oxygen and light. Example: shellac and gelatin
• Coloring agent: Provide color to the compounded product. Example: FD&C Red No. 3.
• Diluents: To add size to very small dosages. Example: starches, calcium salts, and lactose
• Disintegrants: Cause the tablet to swell and burst. Example: Alginic acid, polacrilin potassium, cellulose products, starches
• Enteric coating: Protective layer to prevent dissolution in the stomach. Example: Shellac
• Mask poor taste.
• Flavor sweetener masks bitter falvors. Example: Mannitol.
• Humectant: Prevents preparations from becoming brittle. Example: Glycerin
• Lubricant: Helps keep ingredients form sticking to each other. Example: Magnesium stearate
• Preservative: Prevents the growth of bacteria. Example: Sodium benzoate

Semisolid dosage forms are materials that conform to their container at room temperature. Topical dosage forms deliver drugs into the skin to treat skin disorders. Transdermal dosage forms deliver drugs through the skin into general circulation for systemic effects.