Unit 5 - Semisolid 

Unit 5 - Semisolid Introduction Semi-solid dosage forms are pharmaceutical preparations that have a consistency between solid and liquid. They are mainly intended for external application to the skin or mucous membranes to achieve local or systemic effects. These preparations provide better adherence to the site of application and allow sustained release of the drug. Common examples include ointments, creams, gels, and pastes. Semi-solid formulations are especially useful for delivering drugs to specific areas, offering protective, soothing, or therapeutic effects. Their easy spreadability, stability, and patient acceptability make them one of the most commonly used dosage forms in pharmacy. Ideal Properties of Semi-Solid Dosage Forms Sr. No. Property Description 1 Smooth and Homogeneous Texture The preparation should be uniform, free from lumps, grittiness, or phase separation. It ensures easy application and provides patient comfort during use. 2 Non-Irritant and Non-Sensitizing The formulation should not cause irritation, redness, or allergic reactions on the skin or mucous membranes. Suitable for sensitive areas and long-term application. 3 Good Spreadability and Consistency Should spread easily over the skin with minimal effort, ensuring uniform application and better patient compliance. 4 Stable Physical and Chemical Properties Must remain physically stable (no phase separation or microbial growth) and chemically stable so the active ingredient doesn’t degrade over time. 5 Controlled Drug Release Should provide a uniform and sustained release of the drug to maintain a steady therapeutic effect at the site of application. 6 Good Absorption and Penetration Must allow effective penetration of the drug through the skin or mucous membranes to reach the target site for better bioavailability. 7 Easily Removable Should be easily washable with water or wiped off without leaving sticky or greasy residues, improving user comfort. 8 Aesthetic Appeal and Acceptable Odor Should have a pleasant color, odor, and appearance and be non-greasy for better patient acceptance, especially for cosmetic use. 9 Compatibility with Skin and Ingredients Must be compatible with the skin, drug, and excipients. No chemical or physical incompatibility should occur. 10 Microbial Stability Should resist microbial contamination and contain appropriate preservatives to prevent bacterial or fungal growth. 11 Non-Staining and Non-Greasy Nature Should not stain clothes or make the skin excessively oily, maintaining cleanliness and comfort. 12 Ease of Manufacturing and Packaging The formulation should be easy to prepare on a large scale and compatible with packaging materials such as tubes or jars. 13 Therapeutic Effectiveness Must ensure effective drug delivery to achieve the desired pharmacological action at the site of application. Classification Based on Physical Form 1. Ointments 2. Creams 3. Gels 4. Pastes 5. Poultices Ointments :- Ointments are semi-solid preparations intended for external application to the skin or mucous membranes. They are used to deliver medicaments either locally or systemically, depending on the purpose and the drug used. Ointments provide a protective, emollient, or therapeutic effect and are usually formulated using a base that determines their consistency and behavior. Common ointment bases include hydrocarbon bases (like petrolatum), absorption bases, water-removable bases, and water-soluble bases. The choice of base depends on factors such as the desired drug release, type of skin condition, and ease of removal. Ointments are smooth, non-gritty, and spread easily on application. They can provide an occlusive effect, which helps retain moisture and enhance drug penetration. Depending on the drug and base, they can act as protective, antiseptic, anti-inflammatory, or antibiotic preparations. Ointments are typically prepared by methods like fusion or trituration, ensuring uniform distribution of the drug in the base. They are stored in well-closed containers to prevent contamination and drying. Creams :- Creams are semi-solid emulsions intended for external application to the skin or mucous membranes. They consist of two immiscible phases—an oil phase and a water phase—with one dispersed in the other using an emulsifying agent. Depending on the composition, creams are classified as oil-in-water (O/W) creams, which are non-greasy and easily washable, or water-in-oil (W/O) creams, which are greasier and provide better skin protection. Creams are smooth, soft, and easily spreadable, making them highly acceptable to patients. They are used for both medicated and non-medicated purposes. Medicated creams deliver active ingredients such as antifungal, antibacterial, or anti-inflammatory agents, while non-medicated creams serve as moisturizers, emollients, or protective barriers. The formulation of creams involves careful selection of emulsifiers, stabilizers, and preservatives to ensure stability, uniformity, and safety. They are commonly prepared by the fusion method, where both phases are heated separately and then mixed to form a uniform emulsion. Creams are preferred over ointments when a non-greasy, cosmetically elegant preparation is desired, especially for use on visible or hairy areas of the skin. Their pleasant texture, cooling sensation, and ease of removal make them one of the most popular semi-solid dosage forms in pharmaceutical and cosmetic applications. Gels :- Gels are semi-solid systems in which a liquid phase is dispersed within a three-dimensional network of gelling agents, giving the preparation a jelly-like consistency. They are usually transparent or translucent and provide a cooling and soothing effect upon application to the skin or mucous membranes. Gels are widely used for topical, ophthalmic, vaginal, and oral applications, depending on the drug and formulation type. Gels are mainly classified into hydrogels (water-based) and organogels (non-aqueous, using organic solvents). Common gelling agents include carbopol, gelatin, cellulose derivatives, and sodium alginate, which form a stable matrix capable of holding large amounts of liquid. These formulations are non-greasy, easily washable, and spread smoothly, making them highly acceptable to patients. One of the main advantages of gels is their ability to release drugs in a controlled manner and allow rapid absorption through the skin due to their high water content. They are especially suitable for conditions where a cooling, non-staining, and fast-absorbing formulation is desired, such as in pain relief, burns, or inflammatory skin disorders. Gels are typically prepared by dispersing the gelling agent in the solvent under controlled conditions and adjusting pH to achieve the desired consistency. Pastes :- Pastes are semi-solid preparations that contain a high proportion of finely powdered solid materials (usually 25–50%) dispersed in a suitable base. Because of their high solid content, pastes are stiffer, thicker, and less greasy than ointments or creams. They form a protective layer over the skin and are mainly used for protective, soothing, or adsorbent purposes, particularly in conditions like rashes, ulcers, and eczema. Pastes adhere well to the skin and stay in place longer, providing prolonged contact between the drug and the affected area. They are less penetrative compared to ointments, which helps prevent irritation of sensitive or inflamed skin. The solid particles in pastes also absorb moisture and exudates, making them useful in treating oozing skin lesions. Common bases used in pastes include soft paraffin, zinc oxide, starch, and white petrolatum. Pastes are generally prepared by the levigation or fusion method, ensuring even distribution of solids throughout the base. Examples include Zinc Oxide Paste, Starch Paste, and Salicylic Acid Paste. Due to their thickness, pastes are not easily removed by washing with water but can be gently wiped off. They are typically stored in wide-mouthed containers to allow easy application. Poultices :- Poultices, also known as cataplasms, are soft, moist semi-solid preparations that are applied warm to the skin to provide soothing, healing, or counter-irritant effects. They are generally made from natural substances such as vegetable materials (like linseed, bran, or bread) mixed with a suitable base (e.g., glycerin, kaolin, or bentonite) and water to form a thick paste. The preparation is spread on a piece of cloth, gauze, or muslin and then applied directly to the affected area while warm. The warmth and moisture of a poultice help increase blood circulation, reduce inflammation, and promote the drainage of pus or toxins from inflamed tissues. Poultices are commonly used to relieve pain, swelling, boils, abscesses, and muscular aches. They work by maintaining local heat and moisture at the site of application, which softens the tissues and enhances the healing process. Poultices are typically prepared freshly before use to ensure warmth and consistency. They should be applied at a comfortable temperature—not too hot—to avoid skin burns. After application, the poultice is usually covered with a bandage or cloth to retain heat. Once it cools or dries, it is replaced with a fresh one. Examples include Kaolin Poultice and Linseed Poultice. Mechanism of Skin Permeation: The process of skin permeation involves the movement of a drug from the surface of the skin into the deeper layers and eventually into systemic circulation. The outermost layer, the stratum corneum, acts as the primary barrier that limits drug absorption. Drugs can penetrate the skin through three main pathways: transcellular, intercellular, and transappendageal routes. In the transcellular route, the drug passes directly through the cells of the stratum corneum, while in the intercellular route, it diffuses between the lipid layers surrounding these cells. The transappendageal route allows drugs to pass through skin appendages such as hair follicles and sweat glands. Once the drug crosses the epidermis and dermis, it reaches the blood capillaries, allowing absorption into the systemic circulation for therapeutic action.


Introduction

Semi-solid dosage forms are pharmaceutical preparations that have a consistency between solid and liquid. They are mainly intended for external application to the skin or mucous membranes to achieve local or systemic effects. These preparations provide better adherence to the site of application and allow sustained release of the drug. Common examples include ointments, creams, gels, and pastes. Semi-solid formulations are especially useful for delivering drugs to specific areas, offering protective, soothing, or therapeutic effects. Their easy spreadability, stability, and patient acceptability make them one of the most commonly used dosage forms in pharmacy.

 

Ideal Properties of Semi-Solid Dosage Forms

Sr. No.

Property

Description

1

Smooth and Homogeneous Texture

The preparation should be uniform, free from lumps, grittiness, or phase separation. It ensures easy application and provides patient comfort during use.

2

Non-Irritant and Non-Sensitizing

The formulation should not cause irritation, redness, or allergic reactions on the skin or mucous membranes. Suitable for sensitive areas and long-term application.

3

Good Spreadability and Consistency

Should spread easily over the skin with minimal effort, ensuring uniform application and better patient compliance.

4

Stable Physical and Chemical Properties

Must remain physically stable (no phase separation or microbial growth) and chemically stable so the active ingredient doesn’t degrade over time.

5

Controlled Drug Release

Should provide a uniform and sustained release of the drug to maintain a steady therapeutic effect at the site of application.

6

Good Absorption and Penetration

Must allow effective penetration of the drug through the skin or mucous membranes to reach the target site for better bioavailability.

7

Easily Removable

Should be easily washable with water or wiped off without leaving sticky or greasy residues, improving user comfort.

8

Aesthetic Appeal and Acceptable Odor

Should have a pleasant color, odor, and appearance and be non-greasy for better patient acceptance, especially for cosmetic use.

9

Compatibility with Skin and Ingredients

Must be compatible with the skin, drug, and excipients. No chemical or physical incompatibility should occur.

10

Microbial Stability

Should resist microbial contamination and contain appropriate preservatives to prevent bacterial or fungal growth.

11

Non-Staining and Non-Greasy Nature

Should not stain clothes or make the skin excessively oily, maintaining cleanliness and comfort.

12

Ease of Manufacturing and Packaging

The formulation should be easy to prepare on a large scale and compatible with packaging materials such as tubes or jars.

13

Therapeutic Effectiveness

Must ensure effective drug delivery to achieve the desired pharmacological action at the site of application.

 

Classification

Based on Physical Form

1.     Ointments

2.     Creams

3.     Gels

4.     Pastes

5.     Poultices

 

Ointments :- Ointments are semi-solid preparations intended for external application to the skin or mucous membranes. They are used to deliver medicaments either locally or systemically, depending on the purpose and the drug used. Ointments provide a protective, emollient, or therapeutic effect and are usually formulated using a base that determines their consistency and behavior. Common ointment bases include hydrocarbon bases (like petrolatum), absorption bases, water-removable bases, and water-soluble bases. The choice of base depends on factors such as the desired drug release, type of skin condition, and ease of removal.

Ointments are smooth, non-gritty, and spread easily on application. They can provide an occlusive effect, which helps retain moisture and enhance drug penetration. Depending on the drug and base, they can act as protective, antiseptic, anti-inflammatory, or antibiotic preparations. Ointments are typically prepared by methods like fusion or trituration, ensuring uniform distribution of the drug in the base. They are stored in well-closed containers to prevent contamination and drying.

Creams :- Creams are semi-solid emulsions intended for external application to the skin or mucous membranes. They consist of two immiscible phases—an oil phase and a water phase—with one dispersed in the other using an emulsifying agent. Depending on the composition, creams are classified as oil-in-water (O/W) creams, which are non-greasy and easily washable, or water-in-oil (W/O) creams, which are greasier and provide better skin protection.

Creams are smooth, soft, and easily spreadable, making them highly acceptable to patients. They are used for both medicated and non-medicated purposes. Medicated creams deliver active ingredients such as antifungal, antibacterial, or anti-inflammatory agents, while non-medicated creams serve as moisturizers, emollients, or protective barriers.

The formulation of creams involves careful selection of emulsifiers, stabilizers, and preservatives to ensure stability, uniformity, and safety. They are commonly prepared by the fusion method, where both phases are heated separately and then mixed to form a uniform emulsion. Creams are preferred over ointments when a non-greasy, cosmetically elegant preparation is desired, especially for use on visible or hairy areas of the skin. Their pleasant texture, cooling sensation, and ease of removal make them one of the most popular semi-solid dosage forms in pharmaceutical and cosmetic applications.

Gels :- Gels are semi-solid systems in which a liquid phase is dispersed within a three-dimensional network of gelling agents, giving the preparation a jelly-like consistency. They are usually transparent or translucent and provide a cooling and soothing effect upon application to the skin or mucous membranes. Gels are widely used for topical, ophthalmic, vaginal, and oral applications, depending on the drug and formulation type.

Gels are mainly classified into hydrogels (water-based) and organogels (non-aqueous, using organic solvents). Common gelling agents include carbopol, gelatin, cellulose derivatives, and sodium alginate, which form a stable matrix capable of holding large amounts of liquid. These formulations are non-greasy, easily washable, and spread smoothly, making them highly acceptable to patients.

One of the main advantages of gels is their ability to release drugs in a controlled manner and allow rapid absorption through the skin due to their high water content. They are especially suitable for conditions where a cooling, non-staining, and fast-absorbing formulation is desired, such as in pain relief, burns, or inflammatory skin disorders. Gels are typically prepared by dispersing the gelling agent in the solvent under controlled conditions and adjusting pH to achieve the desired consistency.

Pastes :- Pastes are semi-solid preparations that contain a high proportion of finely powdered solid materials (usually 25–50%) dispersed in a suitable base. Because of their high solid content, pastes are stiffer, thicker, and less greasy than ointments or creams. They form a protective layer over the skin and are mainly used for protective, soothing, or adsorbent purposes, particularly in conditions like rashes, ulcers, and eczema.

Pastes adhere well to the skin and stay in place longer, providing prolonged contact between the drug and the affected area. They are less penetrative compared to ointments, which helps prevent irritation of sensitive or inflamed skin. The solid particles in pastes also absorb moisture and exudates, making them useful in treating oozing skin lesions.

Common bases used in pastes include soft paraffin, zinc oxide, starch, and white petrolatum. Pastes are generally prepared by the levigation or fusion method, ensuring even distribution of solids throughout the base. Examples include Zinc Oxide Paste, Starch Paste, and Salicylic Acid Paste.

Due to their thickness, pastes are not easily removed by washing with water but can be gently wiped off. They are typically stored in wide-mouthed containers to allow easy application.

Poultices :- Poultices, also known as cataplasms, are soft, moist semi-solid preparations that are applied warm to the skin to provide soothing, healing, or counter-irritant effects. They are generally made from natural substances such as vegetable materials (like linseed, bran, or bread) mixed with a suitable base (e.g., glycerin, kaolin, or bentonite) and water to form a thick paste. The preparation is spread on a piece of cloth, gauze, or muslin and then applied directly to the affected area while warm.

The warmth and moisture of a poultice help increase blood circulation, reduce inflammation, and promote the drainage of pus or toxins from inflamed tissues. Poultices are commonly used to relieve pain, swelling, boils, abscesses, and muscular aches. They work by maintaining local heat and moisture at the site of application, which softens the tissues and enhances the healing process.

Poultices are typically prepared freshly before use to ensure warmth and consistency. They should be applied at a comfortable temperature—not too hot—to avoid skin burns. After application, the poultice is usually covered with a bandage or cloth to retain heat. Once it cools or dries, it is replaced with a fresh one.

Examples include Kaolin Poultice and Linseed Poultice.

 

Mechanism of Skin Permeation:
The process of skin permeation involves the movement of a drug from the surface of the skin into the deeper layers and eventually into systemic circulation. The outermost layer, the stratum corneum, acts as the primary barrier that limits drug absorption. Drugs can penetrate the skin through three main pathways: transcellular, intercellular, and transappendageal routes. In the transcellular route, the drug passes directly through the cells of the stratum corneum, while in the intercellular route, it diffuses between the lipid layers surrounding these cells. The transappendageal route allows drugs to pass through skin appendages such as hair follicles and sweat glands. Once the drug crosses the epidermis and dermis, it reaches the blood capillaries, allowing absorption into the systemic circulation for therapeutic action.




Factors Influencing Dermal Drug Penetration

·       The penetration of drugs through the skin is a complex process influenced by several interrelated factors that determine how efficiently a drug can pass through various skin layers and reach systemic circulation or the site of action. The skin acts as a barrier, primarily due to the stratum corneum, which is the outermost layer consisting of keratinized cells embedded in lipid matrices.  The ability of a drug to cross this barrier depends on both the physicochemical properties of the drug and the physiological conditions of the skin.

·       One major factor influencing dermal penetration is the physicochemical nature of the drug itself. The molecular weight of the drug plays a crucial role, as smaller molecules (generally below 500 Daltons) penetrate more easily than larger ones.

·       The lipid solubility or lipophilicity of a drug also significantly affects absorption since the stratum corneum is lipid-rich, allowing lipophilic drugs to diffuse more readily. However, a balance between lipophilicity and hydrophilicity is necessary because after passing the lipid-rich stratum corneum, the drug encounters the aqueous viable epidermis and dermis, requiring some degree of water solubility for effective diffusion.

·       The ionization of the drug is another key determinant; non-ionized or unionized forms of weak acids or bases penetrate better than ionized forms, as they are more lipid-soluble.

·       The concentration gradient across the skin influences penetration—higher drug concentration increases the driving force for diffusion according to Fick’s law.

·       The partition coefficient, representing the balance between lipid and aqueous solubility, must also be optimal for efficient absorption.

·       The type and formulation of the vehicle or base in which the drug is delivered also greatly influence penetration. Ointments, creams, gels, and patches all have different effects on the rate and extent of absorption.

·       Vehicles that hydrate the stratum corneum, such as occlusive formulations, enhance penetration by disrupting lipid packing and increasing permeability.

·       Solvents like alcohol, propylene glycol, and dimethyl sulfoxide (DMSO) can act as penetration enhancers by increasing drug solubility and altering the structure of the stratum corneum.

·       The presence of surfactants and emulsifiers in formulations may also improve drug diffusion by reducing surface tension and fluidizing lipid domains in the skin barrier.

·       The condition of the skin itself is another crucial factor.

·       Healthy, intact skin provides maximum resistance to penetration, whereas damaged, abraded, or diseased skin (as in eczema, psoriasis, or burns) allows for greater drug permeation due to disruption of the stratum corneum.

·       The thickness of the skin varies across body sites; for example, the skin on the soles and palms is thicker and less permeable than that on the face or scrotum, where penetration is significantly higher.

·       Hydration of the skin increases permeability because water swells the stratum corneum, loosening the lipid matrix and allowing more diffusion pathways.

·       The presence of hair follicles and sweat glands also provides alternate routes for drug entry known as shunt pathways, especially for hydrophilic or large molecules that cannot diffuse through the intact stratum corneum.

·       Physiological factors such as age, temperature, and blood flow further modify drug absorption.

·       Infants and elderly individuals often exhibit greater skin permeability due to thinner or less effective barriers.

·       Elevated skin temperature or local blood flow enhances penetration by increasing molecular motion and maintaining the concentration gradient through rapid clearance of absorbed drug from the dermis.

·       Environmental humidity can also affect hydration levels of the stratum corneum, indirectly modifying drug transport.

·       The use of external enhancers or techniques such as iontophoresis, sonophoresis, microneedles, and chemical enhancers can alter dermal penetration artificially by disrupting the barrier or driving the drug into deeper layers using electrical, ultrasonic, or mechanical means.