3. semisolids

Semisolids

  • Semisolid dosage forms are commonly used for treating topical ailments.

  • Primarily used for skin applications but also for ophthalmic, nasal, buccal, rectal, and vaginal treatments.

  • Categories of drugs included:

    • Antibacterials

    • Antifungals

    • Antivirals

    • Local anesthetics

    • Anti-inflammatories

    • Analgesics

Topical Applications

  • Topical applications can be designed for:

    • Local effects: directed at skin for dermal disorders (e.g., dermatitis).

    • Systemic absorption: drugs delivered through skin to general circulation.

    • Products must differ based on the targeting of the skin.

Classification of Semisolids

  • Semisolids are classified into several categories:

    • Ointments

    • Creams

    • Gels

    • Pastes

    • Liniments

Rheological Properties of Semisolids

  • Semisolids exhibit plastic flow; they do not flow until reaching a yield value.

  • Ointment: Non-Newtonian flow with high rheological parameters.

  • Cream: Non-Newtonian flow with low rheological parameters due to the mixture of liquid and solid phases.

  • Gels: Rheological properties influenced by low concentrations of gelling agents.

Ointments and Pastes

  • Ointments:

    • Semisolid systems, applied externally (skin, mucous membranes).

    • Used for infections and inflammation or as emollients/lubricants.

  • Pastes:

    • Higher drug concentration (up to 50% w/w).

    • Stiffer than ointments, effective in absorption of secretions.

    • Not suitable for hairy areas due to stiffness.

Ointment Bases

  • Bases classified by composition into four groups (USP):

    • Hydrocarbon bases (oleaginous bases)

    • Absorption bases

    • Water-removable bases

    • Water-soluble bases

Hydrocarbon Bases

  • Made from oleaginous materials;

    • Emollient effect, moisture retention, occlusive dressings.

    • Powders can be added, but aqueous phases are difficult to incorporate.

    • Difficult to remove due to oily nature.

    • Examples: Petrolatum USP, White petrolatum USP, Yellow ointment USP.

Petrolatum

  • An inert, petroleum-derived substance with branched/unbranched hydrocarbons.

  • Soft, pale yellow, melts at 38°C to 60°C.

  • Used alone or in combination as an ointment base (e.g., Vaseline).

White Petrolatum

  • Purified mix of hydrocarbons, lighter in color, considered more aesthetically pleasing.

  • Commercial product: White Vaseline.

Yellow Ointment

  • Formula:

    • Yellow wax (50g), petrolatum (950g) for 1,000g ointment.

    • Melting process followed by cooling with stirring.

  • White Ointment: Substitutes white wax and white petrolatum for yellow components.

Absorption Bases

  • Two types:

    • Those allowing incorporation of aqueous solutions (e.g., Hydrophilic Petrolatum).

    • Those that are already water-in-oil emulsions (e.g., lanolin).

  • Useful for emollient purposes but do not provide strong occlusion.

  • Not easily removed with water, allowing incorporation of aqueous drug solutions.

Hydrophilic Petrolatum

  • Formula for 1,000g:

    • Cholesterol (30g), Stearyl alcohol (30g), White wax (80g), White petrolatum (860g).

  • Absorbs water, forming water-in-oil emulsion.

  • Commercial products: Aquaphor, Aquabase; can absorb ~three times their weight in water.

Anhydrous Lanolin

  • Pure wax-like substance from sheep wool, cleaned and deodorized.

  • Can mix with double its weight in water to form a water-in-oil emulsion.

Lanolin (Hydrous)

  • Refined, decolorized substance containing 25-30% water.

  • Additional water may be incorporated easily.

  • Modified Lanolin: treated to reduce free lanolin alcohol and contaminants.

Yellow Wax

  • Derived from honeycombs, practically insoluble in water, melts at 61-65°C.

  • Used in hydrophobic ointments for viscosity-enhancing properties (up to 20% concentration).

Water-Removable Bases

  • Oil-in-water emulsions that allow large aqueous phase incorporation.

  • Easily removable from the skin; suitable for exudates absorption.

  • Example: Hydrophilic ointment USP.

Hydrophilic Ointment USP

  • Formula for 1,000g:

    • Methylparaben (0.25g), Propylparaben (0.15g), Sodium lauryl sulfate (10g), Propylene glycol (120g), Stearyl alcohol (250g), White petrolatum (250g), Purified water (370g).

Methods of Preparation of Ointments

  • Ointments can be prepared using two methods:

    • Incorporation: mixing base and components manually.

    • Fusion: melting components together then cooling.

Incorporation Method

  • Involves mixing the base with powdered drug components, using levigating agents when necessary.

  • Geometric dilution technique ensures uniformity when mixing.

Fusion Process

  • Involves melting some or all components together and cooling while stirring until congealed.

    • Components with the highest melting points are added first.

Packaging, Storage, and Labeling

  • Ointments may be packaged in jars or tubes.

  • Requires cool storage and well-closed containers to prevent contamination.

  • Must include labeling for storage conditions, dosing, and administration.

Evaluation of Semisolids

  • Minimum Fill Test: ensures contents meet labeled amounts, assesses content uniformity.

  • Steps: records weights, and the difference gives product weight.

  • Compliance with USP requirements for net content must be adhered to.

Water Content Test

  • Evaluates stability of ointments by determining water content using titrimetric methods, often involving Karl Fischer agents.

  • Presence of water may affect microbial and chemical stability.

Microbial Screening

  • Requires screenings for microbial content (e.g., Staphylococcus aureus, Pseudomonas aeruginosa).

  • Special testing for specific preparations used rectally or vaginally to include yeast and molds.

Metal Particles Test

  • Specific to ophthalmic ointments, evaluates for particles that could irritate the eye.

  • Limits set on quantity of particles allowed.

Leakage Test

  • Assesses seal integrity of ophthalmic ointments; checks for leakages from tubes.

  • Tests conducted in batches to ensure quality control.

Sterility Tests

  • Ensures absence of microbial contamination in ophthalmic semisolids.

  • Techniques include membrane filtration or direct inoculation methods.

Assay

  • Determines the quantity of active drug present using various methods (spectrophotometric, chromatographic).

  • Selection of method based on drug type and product requirements.

In Vitro Drug Release Studies

  • Conducted to evaluate release rate of the drug from the ointment formulation.