Ointments and Semi-Solid Dosage Forms

Overview of Semi-Solid Dosage Forms

• Semi-solid dosage forms include ointments, creams, gels, and pastes and are designed for external application to the skin or mucous membranes.
• The forms serve to protect injured areas, hydrate skin, and transport medication.
• Applications range from local to systemic effects.

Types of Semi-Solid Dosage Forms

• Ointments are greasy, occlusive, and effective for delivering medications to the skin.
• Creams are emulsions that are easily spreadable and water-soluble, suitable for various skin conditions.
• Gels are clear, jelly-like substances that can provide cooling effects and are often used for topical applications.
• Pastes are thicker than ointments for better occlusion and are effective in absorbing serous discharge.
• Lotions are fluid preparations that are less viscous than creams and are often used for lubrication.

Mechanism of Skin Penetration

• Effective absorption requires both aqueous and lipid solubility.
• Drug and vehicle physicochemical properties and the condition of the skin influence drug penetration.
• Log P ratio is crucial for determining drug solubility characteristics.

Formulation and Compounding of Semi-Solid Dosage Forms

• Oleaginous bases are hydrophobic, anhydrous, and water-insoluble, making them occlusive and protective, examples include hydrocarbons.
• Absorption bases are intermediate between oleaginous and water-in-oil bases and can absorb water, an example is Aquaphor.
• Emulsion bases include water-in-oil (W/O) and oil-in-water (O/W) emulsions with varying water content and properties.
• Water-soluble bases (water-removable bases) are water-soluble and can absorb limited amounts of water, they are also non-greasy and easy to spread.

Ointment Bases

• Five main types: oleaginous, absorption, water-in-oil (w/o), oil-in-water (o/w), and emulsion bases.
• Each base has unique characteristics affecting drug release and stability, such as occlusiveness and emollient properties.
• Appropriate base selection depends on patient needs and drug solubility.

Ideal Properties of Ointments

• Should have a smooth texture and feel pleasant, should be easy to spread, non-dehydrating, viscous, and non-gritty.

Compounding Methods

• Geometric dilution ensures uniform distribution of active incredients.
• Fusion is another compounding method.

Emulsions and their Types

• This method is thermodynamically unstable consisting of at least two immiscible liquid phases.
• Types: oil-in-water (o/w), water-in-oil (w/o), multiple emulsions, and microemulsions.
• Emulsion type affects the delivery and release of active ingredients.

Stability and Quality Control of Semi-Solid Dosage Forms

Signs of Physical Instability:

• Changes in consistency, discoloration, emulsion breakdown, and microbial growth.
• Formulations must remain free of pathogens and contamination
• Regular quality control checks are necessary.

Rheology and Flow Properties

• Critical for understanding semi-solid behavior.
• Includes Newtonian, non-Newtonian, dilatant, and pseudoplastic flows, each affecting product application and absorption.
• Viscosity influences spreadability and absorption.

Creams

• Creams are semi-solid emulsions that can be hydrophobic (W/O) or hydrophilic (O/W).
• Characteristics are opaque, soft, and provide a good alternative when occlusive effects are not necessary

Beyond Use Dates (BUD) and Regulatory Considerations

• BUD is the date after which the compounded preparation is no longer used.
• Storage conditions and formulation stability must be considered when determining BUD.

Water-Soluble Bases Advantage

• Allows for targeted treatment of localized conditions. Is ideal for treating skin issues, such as rashes or infections, associated with membranes.
• It's generally more stable than liquid forms, reducing the risk of degradation

Disadvantage of Water-Soluble Bases

• Can carry a risk of staining.
• Using fingers for application can introduce bacteria, effecting shelf life

Gels

• Are semi-solid systems with a jelly-like consistency due to gelling agents.
• They have a high viscosity and restrict movement of the dispersing medium.

Emulsifying Agents and Greams

• Hydrophilic creams are oil-in-water emulsions that are miscible with water, making them suitable for application on the skin.
• Commonly used in dermatological formulations for moisturizing and therapeutic effects

Rheology

• The study of flow and deformation of matter.

First Pass Metabolism Avoided

• Drugs applied topically bypass the liver, enhancing bioavailability.

Gels Overview

• Semisolid with dispersions of small or large molecules in an aqueous liquid rendered jelly-like by gelling agents.
• Gelling agents undergo cross-linking when hydrated which increases viscosity. Characterized by semi-rigid structure, restricting movement.
• Intended for local effects, administered topically, orally, nasally and rectally. single-phase gels create no apparent boundaries, two-phase gels consist of distinct particles (methylcellulose and carbomer).

Thixotropic properties of gels

• Gels can become less viscous when subjected to shear stress

Single Phase and Two Phase Gels

• Single Phase: Have a uniform distribution of macromolecules, includes natural polymers
• Two Phase: consist of floccules of small distinct particles, often involving inorganic compounds such as aluminum hydroxide gel.

Gelling Agents

• Cellulose derivatives, such as methylcellulose, are widely used for their thickening properties.
• The solubility of gelling agents can be temperature and pH dependent, which affects the final product

Mucilage Properties

• Specific type of single-phase gel made from synthetic or natural macromolecules

Carbomer gels

• Require neutralizers or pH adjusting chemicals to achieve the desired viscosity

Full Solidification

• Full solidification of gels can take from 24 to 48 hours

Evaluation and Quality Control of Semisolids

• PH testing is important for safety and stability.
• Microbial testing for especially for Ocular Use.
• Requires tight containers and appropriate temperatures.

Dosage

• The solubility of the drug in the base affects how long it remains in the formulation. Consider whether the treatment is topical or systemic, as this influences base choice.
• Hydrated skin enhances absorption of the drug.

Suppository Uses

• Design for insertion into a body office
• Melt, soften, or dissolve to expert local or systemics effects

Suppository Preparation Methods

• Melting points ranging from 18°C to 35°C, which additives can alter.
• Overheating cocoa butter can lead to instability; it should not exceed 35°C during processing.
• Synthetic triglycerides avoid cocoa butter's issues and offer stability and water absorption.
• Glycerinated gelatin and polyethylene glycol (PEG) bases have hygroscopicity and irritation.

Hand Rolling Batch

• is the simplest method for small batches but requires skill.
• Compression molding involves forcing the drug and base into a mold, suitable for larger production

Fusion Molding

• Fusion molding melts the base before adding the drug, though it's less common today.

Melting Range Test for Quality Control

• Melting range tests determine the temperature at which the suppository melts

BUDS for Compounded Non Sterile Products

• BUD is crucial indicating the time frame for safe use
• The non reserved of aqueous forms of products
• Bydrate is 14 days when refrigerated

The stratum corneum

• The rate limiting step for transdermal drug delivery is the ability of the drug to cross the Stratum Corneum acts as a semipermeable membrane.
• Composed of keratinized tissue, lipids, and water, influencing drug permeability The thickness is around 10µm must traverse

TDD: Transport Mechanisms

• Requires Transdermal drug transport include transepidermal, transappendageal, and intercellular routes.
• The transappendageal (through the appendage) route limited because the area makes up only 0.1%

The First FDA APPoved TDD

• For Scopalmine in 1979

Solubility & MW Impact absorption

• The best solubility is below 400 but Ideally higher for a TDD

The rate limiting step for transdermal drug delivery

• This is Stratum Corneum acting as semipermeable membrane,

Transappendageal route to the Skin

• Transappendageal route involves drug transport through hair follicles and sweat glands molecules,

Log P ideal range for transdermal drug delivery:

• Log P ideal range for TDD: 1 to 3

Key factors to consider

• Drug Penetration Factors affecting drug absorption through the skin, including solubility and the nature of the base

Key transport mechanisms

Drug transport across the epidermis, either inter cellular drugs

First commercially patch

In december 1979 was approved for use

Formula for permeability coefficient:

P = DK/h

The Franz diffusion cell

Commonly used to measure drug permeability through skin models

Application Guidelines for TDD

• Rotation of patches required
• Use clean and dry skin area
• Avoid lotions
• Free from har

Key layers of the skin and describe each layer:

1.Epidermis: The outermost layer, about 0.05 mm thick in eyelids and 1.5 mm thick in palms and soles. 2. Dermis: The layer beneath the epidermis, supports,provides structural support and containing blood vessels 3. Subcutaneous Tissue: Is the deepest layer, consisting of fat and connective tissue, cushioning

Three primary layers of the skin:

• Epidermis providing barrier
• Subcutaneous that include blood supply and cushioning and elasticity
• Dermis anchors the skin to underlying structures

TDD: Key Advantages

• It reduces drug degredation.
• Non invasive nature

TDD: Disadvantages

• Poor skin protection
• Lead to Inconsistent drug absorptions patients

Factors Affecting Drug Absorption in TDD

• Drug Concentration
• Surface
• Hydration
• Skin temperature

Biological Factors Affection in TDD

• Metabilism
• Patient age
• Medication intake
• Blood Flow

TDDS: Introduction

TDDS are designed to deliver drugs the skin. Some offer the same effect while avoiding the GI Trach.

• TDDS can provide controlled Release of Medication for exteded periods of Compliance

Ficks First Law of Diffusion

Describes drug concentration a membrane from low The Permeability coefficient (P) can be calculated using the formula: P=hDxK

Formula Steady State Flux

J=hD×A×(Cd-Cr)

Explore the characteristics and applications of semi-solid dosage forms, including ointments, pastes, and emulsions. Understand their differences, advantages, and uses in skin protection and transdermal drug delivery. Learn about their distinguishing features and suitability for various skin conditions.