Greetings everyone, I am Xiao Zhou. Today we will discuss external preparations. External preparations include ointments, plasters, and patches. We will mainly focus on their classification, as well as the characteristics and types of ointments and creams.
Key Points:
1. Characteristics and Classification of External Ointments
(1) Characteristics of External Ointments External ointments have protective, lubricating, and local therapeutic effects, and can also exert systemic therapeutic effects through the skin or mucous membranes. In transdermal drug delivery systems, drugs penetrate the skin into the systemic circulation, avoiding the first-pass effect in the liver, preventing drug degradation in the gastrointestinal tract, reducing fluctuations in blood drug concentration, and minimizing side effects.
(2) Classification of External Ointments Based on matrix and form: ointments, plasters, and patches.1. Ointments Mainly used for local treatment of the skin. Ointments can be classified into oily and water-soluble ointments based on their matrix composition. Creams are made from emulsified matrices.2. Plasters and Patches Plasters can be classified based on matrix composition: rubber plasters made primarily from rubber; gel plasters made from hydrophilic polymer materials. Patches refer to thin preparations made from raw medicinal materials and suitable materials that can be adhered to the skin to produce systemic or local effects.3. Medicinal Plasters Medicinal plasters are made from slices of medicinal herbs, edible vegetable oils, and red lead (lead oxide) or white lead (lead powder) processed into a paste and applied to backing materials for external use on the skin. The former is called black plaster, while the latter is called white plaster.
2. Pathways and Influencing Factors of Transdermal Drug Absorption
(1) Pathways of Transdermal Drug Absorption The transdermal absorption of drugs in external ointments includes three stages: release, penetration, and absorption. Release – the drug is released from the matrix; Penetration – the drug penetrates through the epidermis into the dermis; Absorption – through blood vessels and lymphatic vessels into the systemic circulation to produce systemic effects. The pathways for transdermal absorption of external ointments include: intact epidermis; hair follicles, sebaceous glands, and sweat glands, which are accessory organs of the skin. It is generally believed that the main pathway for drug absorption is through the stratum corneum cells and their intercellular spaces of the intact epidermis, while the accessory organs of the skin occupy a smaller area and are not the main pathways for absorption.
(2) Factors Influencing Transdermal Drug Absorption
1. Skin Conditions: (i) Application site; (ii) Skin lesions; (iii) Skin temperature and humidity; (iv) Skin cleanliness. 2. Drug Properties: Drugs with suitable oil-water partition coefficients, possessing both lipophilicity and hydrophilicity, are ideal for transdermal absorption. Transdermal absorption preparations should preferably use drugs with relatively low molecular weights and strong pharmacological effects.
3. Composition and Properties of the Matrix
(1) Composition, Type, and Properties of the Matrix directly affect the release, penetration, and absorption of drugs. It is generally believed that drug absorption is best in emulsified matrices, followed by hydrophilic ointment matrices (such as petroleum jelly mixed with lanolin), silicones, and least effective in hydrocarbon matrices. If the composition of the matrix is similar to sebaceous secretions, it facilitates the penetration of certain drugs through the skin. Water-soluble matrices like polyethylene glycol release drugs quickly but have little effect on drug penetration, making the resulting ointments difficult for transdermal absorption.
(2) pH of the Matrix: Affects the absorption of acidic and basic drugs. When the pH of the matrix is less than the pKa of weakly acidic drugs or greater than the pH of weakly basic drugs, the molecular form of the drug significantly increases, facilitating absorption.(3) Additives: Adding surfactants and transdermal penetration enhancers to the matrix can increase the permeability of drugs, aiding absorption.
(4) Matrix’s Effect on Skin Hydration: Matrices that increase skin hydration can enhance drug permeability. Oily matrices, which have strong occlusive properties, can significantly increase skin hydration.
(5) Other Factors: In addition to the aforementioned influencing factors, transdermal drug absorption is also closely related to drug concentration, application area, frequency of application, and contact time with the skin.
3. Ointments and Creams
(1) Characteristics of Ointments and Creams Ointments refer to uniform semi-solid external preparations made by mixing raw medicinal materials with oily or water-soluble matrices. Creams refer to uniform semi-solid preparations formed by dissolving or dispersing raw medicinal materials in emulsified liquid matrices. Ointments and creams are often used for chronic skin diseases, providing protective effects on wounds, lubricating the skin, and local therapeutic effects; the transdermal absorption of drugs in ointments can also produce systemic therapeutic effects.
(2) Quality Requirements and Types of Ointment and Cream Matrices Ointments consist of drugs and matrices. Common matrices are divided into oily and water-soluble types. Creams made from emulsified liquid matrices can be classified into water-in-oil (W/O) and oil-in-water (O/W) types.
Characteristics, Representative Varieties, and Applications of Oily, Emulsified, and Water-Soluble Matrices
1. Oily Matrices
(1) Characteristics of Oily Matrices: Oily matrices include fats, lipids, hydrocarbons, etc. Their main characteristics are lubrication, non-irritating, ability to occlude the skin surface, and promote skin hydration, providing better protection and softening of the skin compared to other matrices. They can be compatible with various drugs. However, they are greasy and hydrophobic, leading to poor drug release, difficulty in mixing with aqueous liquids, and not easily washed off with water, making them unsuitable for acute inflammatory wounds with significant exudation.
(2) Representative Varieties and Applications: Oily matrices mainly include fats, lipids, hydrocarbons, and silicones. 1) Fats: Commonly used are animal and vegetable oils, hydrogenated vegetable oils, etc. Vegetable oils are often combined with waxes of higher melting points to form matrices of suitable consistency, such as traditional Chinese medicinal ointments often use sesame oil mixed with beeswax as the matrix. 2) Lipids: i. Lanolin: Due to its composition being similar to sebaceous secretions, it can enhance the permeability of drugs in ointments. It is often used in combination with petroleum jelly to adjust its permeability and hydrophilicity. ii. Beeswax: Commonly used to adjust the consistency of ointments or increase stability. Other types include white wax and spermaceti, mainly used to increase the consistency of the matrix.
3) Hydrocarbons: i. Petroleum Jelly: When combined with appropriate amounts of lanolin, cetyl alcohol, or cholesterol, it can increase its hydrophilicity. ii. Paraffin and Liquid Paraffin: Both are mainly used to adjust the consistency of ointments. 4) Silicones: Commonly used dimethyl silicone, which is non-irritating to the skin, does not stain clothing, has good lubricating properties, and is easy to apply. However, it can be irritating to the eyes and is not suitable as a base for eye ointments.
2. Emulsified Matrices
(1) Characteristics of Emulsified Matrices: Emulsified matrices consist of aqueous phase, oily phase, and emulsifiers. Emulsified matrices are divided into water-in-oil (W/O) and oil-in-water (O/W) types. Due to the action of surfactants, these matrices have a certain affinity for both oil and water, facilitating drug release and penetration, absorbing exudates from wounds, and are easy to apply and wash off. They can be used for subacute, chronic, and non-exudative skin diseases but are contraindicated for erosive, ulcerative, and purulent wounds. Drugs that are unstable in water should not be made into emulsified ointments.
(2) Representative Varieties and Applications: i. Water-in-Oil (W/O) Emulsified Matrices: Can mix with large amounts of water, non-greasy, and easy to wash off. Drug release and penetration are faster than other matrices, but if the affected area has excessive secretions, the secretions may be reabsorbed into the skin, worsening inflammation, so attention should be paid to the selection of indications. Due to the risk of drying and mold, moisturizers and preservatives are often added. ii. Oil-in-Water (O/W) Emulsified Matrices: Can absorb some moisture but cannot mix with large amounts of water, have good transdermal properties, and excellent spreadability.
3. Water-Soluble Matrices
(1) Characteristics of Water-Soluble Matrices: This type of matrix releases drugs quickly, has no greasiness or irritation, can absorb tissue exudates, and can be used for erosive wounds and mucous membranes, but has poor lubricating properties, is prone to dehydration and mold, so moisturizers and preservatives must be added.
(2) Representative Varieties and Applications: i. Cellulose Derivatives: Commonly used are methylcellulose, sodium carboxymethylcellulose, etc.
ii. Polyethylene Glycol: Often mixed in appropriate proportions of relative molecular weights between 300-6000 to form matrices of suitable consistency.
Exercises:
1. The ointment matrix that is commonly used with petroleum jelly to adjust permeability and hydrophilicity is:
A. Beeswax
B. Paraffin
C. Lanolin
D. Vegetable oil
E. Hydrogenated vegetable oil
2. (Multiple choice) The following belong to water-soluble ointment matrices:
A. Beeswax
B. Glycerin gelatin
C. Polyethylene glycol
D. Liquid paraffin
E. Methylcellulose
3. Regarding the matrix of ointments, the correct statement is:
A. Carbomer is a high-grade fatty acid glycerol ester and its mixture, belonging to water-soluble matrices.
B. Lanolin belongs to lipid matrices, has high hydrophilicity, and good permeability.
C. Petroleum jelly is stable in nature, can be compatible with most drugs, and is especially suitable for wounds with significant acute inflammatory exudation.
D. O/W emulsified matrices release and penetrate drugs faster, suitable for all types of drugs.
E. Polyethylene glycol is commonly used as a matrix for traditional Chinese medicinal ointments.
Answers and Explanations:
1. C
This question tests the ointment matrix. Lanolin (C) is commonly used with petroleum jelly to adjust its permeability and hydrophilicity. Beeswax (A) can serve as an auxiliary emulsifier; paraffin (B) is mainly used to adjust the consistency of ointments, and liquid paraffin can also be used to grind drug powders for easier mixing with the matrix; commonly used animal and vegetable oils, hydrogenated vegetable oils (D and E) are also used; vegetable oils are often combined with waxes of higher melting points to form matrices of suitable consistency, such as traditional Chinese medicinal ointments often use sesame oil mixed with beeswax as the matrix.
2. C, E
This question tests water-soluble ointment matrices. Ointments can be classified into oily and water-soluble types based on their matrix composition. Representative varieties of water-soluble ointment matrices include i. Cellulose Derivatives: commonly used methylcellulose (E), sodium carboxymethylcellulose, etc. Methylcellulose can form complexes with cold water and gel. Carboxymethyl dissolves in both cold and hot water, and at higher concentrations, it appears gel-like. ii. Polyethylene Glycol (C): is a high molecular weight polymer of ethylene glycol. Polyethylene glycol is stable in nature, can be compatible with most drugs, is not prone to rancidity or mold, can mix with water, ethanol, acetone, and chloroform. It has good hygroscopicity, can absorb secretions, and is easy to wash off. Drug release and penetration are fast. It is often mixed in appropriate proportions of relative molecular weights between 300-6000 to form matrices of suitable consistency. However, long-term use may cause skin dehydration and dryness; this product mixed with benzoic acid, tannic acid, phenol, etc., can excessively soften the matrix and reduce the preservative capacity of phenolic preservatives; glycerin gelatin is commonly used as a water-soluble matrix for suppositories (B is incorrect); beeswax is commonly used as a non-water-soluble matrix for pills (A is incorrect); liquid paraffin is a mixture of various liquid hydrocarbons, can mix with most fatty oils or volatile oils. It is mainly used to adjust the consistency of ointments and can also be used to grind drug powders for easier mixing with the matrix (D is incorrect).
3. B
This question tests the matrix of ointments. Lanolin belongs to lipid matrices, has high hydrophilicity, and good permeability (B is correct); carbomer belongs to water-soluble matrices but is not a high-grade fatty acid glycerol ester and its mixture, it is an acrylic acid derivative (A is incorrect); petroleum jelly is stable in nature, can be compatible with most drugs, but has poor hydrophilicity and is not suitable for wounds with significant acute inflammatory exudation (C is incorrect). O/W emulsified matrices release and penetrate drugs faster, but are not suitable for all types of drugs (D is incorrect). Polyethylene glycol is a water-soluble matrix (E is incorrect).
Xiao Zhou, the Pharmacist, says:
First, it is important to clarify which categories external preparations include and what factors influence transdermal drug absorption. Secondly, we discussed the important issue of matrices. Oily matrices mainly include fats, lipids, hydrocarbons, and silicones. Among them, the lipid lanolin is particularly important, as it has been tested many times; it can enhance the permeability of drugs in ointments. It is often used in combination with petroleum jelly to adjust its permeability and hydrophilicity. Other organic substances such as fats, hydrocarbons, and silicones are clearly oily matrices. For water-soluble matrices, remember cellulose derivatives: commonly used methylcellulose, sodium carboxymethylcellulose, and polyethylene glycol. For emulsified matrices, O/W means oil is wrapped outside, which is oily matrices, while W/O means water is wrapped outside, which is water-soluble matrices. The basic concept of what is inside and what is outside must be clearly understood.
