Semisolid Dosage Forms PDF

Semi-solid dosage form Vibhuti Agrahari, PhD OU College of Pharmacy  Learning Resources Format of the course: Lectures, visual aids and practice question and case study TEXTBOOK (recommended): Pharmaceutical Dosage Forms and Drug Delivery Systems. Howard C. Ansel, Llo...

Semi-solid dosage form Vibhuti Agrahari, PhD OU College of Pharmacy  Learning Resources Format of the course: Lectures, visual aids and practice question and case study TEXTBOOK (recommended): Pharmaceutical Dosage Forms and Drug Delivery Systems. Howard C. Ansel, Lloyd V. Allen, and Nicholas G. Edited. 10th Edition, 2013. The Art, Science, and Technology of Pharmaceutical Compounding, Loyd V. Allen, 5th Edition, January 2016, e-ISBN: 1 58212-263-6 Applied Pharmaceutics in Contemporary Compounding, Robert P. Shrewsbury, Edition 3rd, Morton publishing 2  Learning Objectives 1. Enlist types of semisolid dosage form and routes of administration 2. Enlist therapeutic use of semisolid dosage form 3. Explain dermatological preparation – discuss functions of topically applied semi-solids and discuss three examples. 4. Enlist six advantages, and two disadvantages. 5. Discuss properties of semisolid dosage form 6. Understand ointment and its use – medicated and unmedicated ointment 7. Classification of an ointment bases with examples – four types 1) Oleaginous bases 2) Absorption bases (w/o) 3) W/O emulsion base 4) Water removable base/Emulsion bases (o/w) 5) Water soluble or water miscible base 8. Discuss Incorporation of drug in four types ointment bases – Oleaginous, Absorption, Emulsion, Water miscible 9. Describe excipients used in the semisolid preparation  Learning Objectives 10. Two methods of preparation of ointments 11. Two techniques to mix ingredients of ointments Example: A. Incorporation of Solids, B. Fusion 12. Compare and contrast an ophthalmic ointment base and a topical ointment base. 13. Know quality control, storage, packaging, labeling, BUD 14. Describe and define, 1)Creams 2)Gels/Magmas 3)Plasters 4)Pastes 5)Glycerogelatin 15. In class activity – A. Differentiate between ointments, pastes, creams and gels B. Compare between four types of bases C. Discuss different terms  Objective -1 Semi-solid dosage form Pharmaceutical semisolid preparations include ointments, pastes, creams, gels, plasters and glycerogelatin. Topically delivered through skin and considered as topical dosage form. Mainly used for external application, however ophthalmic ointments/gels are also available. Other routes of ointment/creams/gels are rectal, vaginal, nasal (Mupirocine nasal route).  Objective -2 FYI Therapeutic Use: Anti-fungal Anti-pruritic Analgesic Anti-acne Anti-bacterial Anti-infective Protectant  Objective -3 Topical delivery (Dermatological preparation) Topically applied pharmaceuticals have three main functions; 1.to protect the injured area from the environment and permit the skin to rejuvenate; 2.to provide skin with hydration or to produce an emollient effect; 3.to convey a medication to the skin for a specific effect, either topically or systemically (trans-dermal) Examples, an ointment is generally applied to dry, scaly skin a cream is applied to weeping or oozing surfaces a lotion is applied to intertriginous areas (opposing skin surfaces) or where friction may occur, as between the thighs or under the armpit.  Objective - 4 Advantages Used externally First pass gut and hepatic metabolism is avoided Probability of side effect can be reduced Local action Systemic action: transdermal drug delivery Patient compliance Disadvantage No dosage accuracy Base of the semi-solid dosage form can be easily oxidized  Objective -5 Properties FYI Smooth texture, elegant in appearance Non-dehydrating, Non-greasy and non-staining Non-gritty and Non-irritating Do not alter membrane/ skin functioning, miscible with skin secretion FIGURE 10.5 Day ointment roller mill. Standards of fineness and smoothness require that no grains of material be visible under a 10-power microscope after passage through this machine. (Courtesy of Eli Lilly and Company.)  Practice Q -1 Q. What are dermatologic formulations used for? A.to protect the skin or mucous membranes from chemical or physical irritants B.to provide medications for systemic effect C.to provide an emollient (skin softening) effect D.All In addition to those listed above, dermatologic formulations can also be used for a local effect and to provide lubrication between intertriginous areas (areas where skin rubs together).  Ointment and its use – medicated and Objective -6 unmedicated ointment Intended for external application to the skin or mucous membranes. Unmedicated ointments are used as protectants, emollients or lubricants. Example: Cold cream, lip-balm Ointment bases used as vehicles for medicated ointments used topically for antipruritic, kerotolytic, astringents etc.  Practice Q -2 Q. What are ointments generally used for? A.lubrication between intertriginous areas B.protection of the skin C.emollient properties to rehydrate the skin D.All Hint: Ointments are generally used on dry, scaly lesions because their emollient properties will help rehydrate the skin. Ointments also stay on the skin longer than other preparations such as lotions.  Ointment bases Objective -6 A dermatological vehicle is a preparation that releases an active drug to the application site Case – I: Protective ointment: serves to protect the skin against external factors such as air, sunrays. Used on dry scaly skin, lesions. Case – II: An antiseptic ointment is used to destroy or inhibit the growth of bacteria. Frequently bacterial infections are deeply seated; a base which has the capacity to either penetrate or dissolve and release the medication effectively is desired. Stay on the skin for an extended period of time, which aids in drug absorption.  Objective -7 Ointment Bases Four (4) types of ointment bases Differentiated based on their physical composition I. Oleaginous bases II. Absorption bases (w/o) III. Water removable base/Emulsion bases (o/w) IV. Water soluble or water miscible base  Objective -7 and 15 Ointment Bases – Compare and Contrast Compare between four types of bases – let’s consider absorption bases in 2 types because of specific quantity of addition of water into it- NOW 5 types of bases I. Oleaginous bases II. Absorption bases (w/o) III.W/O emulsion base IV. Water removable base/Emulsion bases (o/w) V. Water soluble or water miscible base  Objective -7 (I) Oleaginous Bases Hydrocarbon bases On application to skin they have; Emollient effect Occlusive dressings Protect against the escape of moisture Remain on the skin for long periods without drying out Water and aqueous preparations may be incorporated, but only in small amounts and with difficulty. Examples: White petrolatum, Yellow ointment  FYI Objective -7 Oleaginous Bases Example: White Petrolatum, USP Purified mixture of semisolid hydrocarbons from petroleum Wholly or nearly decolorized Known as white petroleum jelly Yellow Ointment, USP: Following formula; Yellow wax 50 g Petrolatum 950 g Purified wax obtained from honeycomb of the bee.  (II) Absorption Bases Objective -7 Absorption bases are of two types: (A) those that permit incorporation of aqueous solutions resulting in the formation of water-in-oil (W/O) emulsions (e.g., hydrophilic petrolatum USP), (B) those that are W/O emulsions (syn: emulsion bases) that permit incorporation of additional quantities of aqueous solutions; typically, 50% of their volume in water (e.g., lanolin USP) Used as emollients Not easily removed from the skin with water washing, because external phase of emulsion is oleaginous Useful as pharmaceutical adjuncts to incorporate small volumes of aqueous solutions into hydrocarbon bases.  Objective -7 Absorption bases Example: Hydrophilic Petrolatum, USP Hydrophilic Petrolatum, USP, has the following formula for the preparation of 1000 g: Cholesterol 30 g Stearyl alcohol 30 g White wax 80 g White petrolatum 860 g Commercial product, Aquaphor, and useful to help incorporate a water-soluble drug, e.g., tobramycin sulfate  Objective -7 (III) Water-removable/washable Bases  Water-Removable Bases: Example Hydrophilic Objective -7 Ointment, USP Following formula for the preparation of 1000 g: Ingredient Amount (grams) Methylparaben 0.25 Propylparaben 0.15 Sodium lauryl sulfate 10.00 Propylene glycol 120.00 Stearyl alcohol 250.00 White petrolatum 250.00 Purified water 370.00 Sodium lauryl sulfate is the emulsifying agent Stearyl alcohol and white petrolatum constituting the oleaginous phase Propylene glycol/water - Aqueous phase Methylparaben and propylparaben are antimicrobial preservatives  Objective -7 (IV) Water-Soluble Bases Do not contain oleaginous components Water washable and greaseless Mostly used for incorporation of solid substances Polyethylene glycol (PEG) ointment, NF, is the prototype example  Example Water-Soluble Bases: Polyethylene Glycol Ointment (PEG), Objective -7 NF PEG is a polymer of ethylene oxide and represented by the formula H(OCH2CH2)nOH, in which n represents the average number of oxyethylene groups. PEG300, PEG3000 etc. Numeric designations (PEG300, PEG3000) associated with PEGs refer to average molecular weight of polymer. PEGs having average; molecular weight below 500 are clear, colorless liquids molecular weight above 1000 are wax like white materials molecular weight in between are semisolids (500-1000)  Practice Q - 3 Oleaginous bases are water-washable and will absorb water. A) True B) False Practice Q - 4 The properties of ‘Oleaginous bases’ are - A) Anhydrous B)Do not dissolve in water C)Immiscible in water D)Generally, have high viscosity E)All TRUE  Incorporation of drugs Objective -8 Oleaginous Bases – Insoluble drug, pulverize the powder on the pill tile or with a mortar and pestle. Use a levigating agent to wet the powder and then incorporate the wetted powder into the ointment base. Good levigating agent is mineral oil; it is compatible with oleaginous bases. – Soluble drugs can be incorporated into oleaginous bases by fusion. Absorption Bases ▪Oils and insoluble powders can be directly incorporated into the external phase using a pill tile and spatula ▪Water soluble ingredients can be added to water phase of w/o emulsion. ▪Internal or external phase of the emulsion of the drug must be considered when selecting a levigating agent. ✓ If the drug reside in the internal phase (water phase), then the levigating agent should be water soluble. Example; Water, glycerin, alcohol, or propylene ✓ If the drug reside in the external phase, then mineral oil should be used  Incorporation of drugs Objective -8 O/W Emulsion Bases – Water soluble powders can be directly incorporated into the external phase using a pill tile and spatula – Difficult to incorporate oil soluble ingredients into the o/w formulation. A small amount of oil can be incorporated into the base if there is excess emulsifier. Water Miscible Bases Water soluble drugs can be dissolved in a small quantity of water and incorporated using a pill tile and spatula. Insoluble powders will require a water miscible levigating agent. Oils can be added into these bases by first mixing the oil with glycerin or propylene glycol, and then incorporating the mixture into the base.  Practice Q-5 ‘Glycerin, which is miscible with water, is usually used as the levigating agent for water-removable and water-soluble bases. Similarly, mineral oil is the choice for oleaginous bases, such as hydrocarbon, absorption, and water-in-oil emulsion base’. The given statement is: A) True B) False  Objective - 9 Composition/Excipients ❑Stiffeners ❑Humectants ❑Penetration enhancers ❑Antioxidants ❑Preservatives  Composition/Excipients Objective - 9 Stiffeners include waxes that have high melting points (e.g., white wax). Waxes blend into oleaginous bases to enhance the viscosity of a preparation. Humectants, such as glycerin, propylene glycol, or polyethylene glycol (PEG) 300, can be added to a preparation to decrease evaporation rate of water from the preparation. Penetration (absorption) enhancers are agents that can interact sufficiently with sub-cutaneous layer to increase the rate of penetration (absorption) of the drug through the skin. Example: dimethyl sulfoxide Antioxidants, such as butylated hydroxytoluene, required to delay the rate of rancidification of oily bases. Preservative, such as parabens are used to prevent microbial growth for large amount of aqueous base.  Practice Q-6 Q. Stiffeners are used to: A) delay the rate of rancidification B) add as lubricating agent in the preparation C) increase the rate of penetration of the drug through the skin D) enhance the viscosity of a preparation  Ointment preparation and Techniques to mix ingredients Objective 10 Manual Methods of Preparation Involve using a pill tile and spatula or a mortar and pestle. Mechanical Methods of Preparation Mixers (range from hand-held propeller to kitchen mixers). Electronic mortars and pestles (the Unguator) Objective 11 Two techniques depending primarily on nature of the ingredients; 1.Incorporation: components are mixed until a uniform preparation is attained. using a mortar and pestle, or a spatula, ointment slab (pill tile), an ointment mill 2.Fusion: combined by being melted together and cooled with constant stirring until congealed  Objective 11 Incorporation of Solids Prepared by rubbing the components (base and API) together until product is smooth and uniform by geometric dilution Levigating or mixing the solid material in a vehicle in which it is insoluble. Levigating agent used such as; ✓mineral oil for bases in which oils are the external phase ✓glycerin for bases in which water is the external phase For incorporating a gummy material, such as camphor, pulverization by intervention can be used. Fusion Melted together and cooled with constant stirring until congealed Heat-labile substances and any volatile components are added last Substances may be added to the congealing mixture as solutions or as insoluble powders (levigated with a portion of the base). Lab scale- ointment mill large steam-jacketed kettles FIGURE 10.1 Creams and ointments in batch sizes up to 1,500 kg are manufactured in this stainless-steel tank, which has counter sweep agitation and a built-in homogenizer. (Courtesy of Lederle Laboratories.) FIGURE 10.2 Unguator Model B-R Electronic mortar and pestle. (Courtesy of Health Engineering Systems NOT FOR EXAM Know Quality control, Storage, Packaging, Labeling Ophthalmic and a topical ointment base (Objective 12): Topical applications are not required to be sterile except ophthalmic preparations. Objective 13 Quality control Involves checking final preparation for the following characteristics: final weight, visual appearance, color, odor, viscosity, pH, homogeneity, and phase separation Packaging, Storage, And Labeling Packaged either in large-mouth jars or in metal or plastic tubes. stored in well-closed and in a cool place Light-sensitive preparations are packaged in opaque or light-resistant containers. Beyond-use date BUD: 6-months for oleaginous preparation BUD for an extemporaneous preparation is 30-day supply if the preparation contains water.  Creams Objective 14 Contain one or more medicinal agents (API) dissolved or dispersed in either a W/O emulsion or an O/W emulsion or in water-washable base. Opaque, soft solids or thick liquids for external application. Vanishing creams are oil-in-water emulsions containing large percentages of water. Primary application in topical skin products and rectal, vaginal products.  Gels Objective 14 ❑ Semisolid systems consisting of dispersions of small inorganic particles in an aqueous liquid vehicle rendered jellylike by the addition of a gelling agent. ❑ Gelling agents used are ▪ synthetic macromolecules, such as carbomer 934 ▪ cellulose derivatives (carboxymethylcellulose or HPMC) ▪ natural gums (tragacanth) ❑ In addition to the gelling agent, water, and API, it contains; ▪ Solvents: such as alcohol and/or propylene glycol ▪ Preservatives: such as parabens ▪ Stabilizers: such as edetate disodium (EDTA)  Gels Objective 14 A gel mass consisting of floccules of small distinct particles is termed a two-phase system, often referred to as a magma. Example; Milk of magnesia (or magnesia magma), consists of a gelatinous precipitate of magnesium hydroxide. Gels may thicken on standing, forming a thixotrope, and must be shaken before use to liquefy the gel and enable pouring.  Pastes Objective 14 Thick, stiff, do not flow at body temperature Intended for application to the skin. Contains a larger proportion of solid material therefore stiffer. Paste remains in place after application and are effectively employed to absorb serous secretions. Example: Zinc oxide paste (Lassar’s Plain Zinc Paste), prepared by mixing 25% each of zinc oxide and starch with white petrolatum. The product is firm and is better able to protect the skin and absorb secretions.  Plasters Objective 14 Plasters are solid or semisolid adhesive masses spread on a backing of paper, fabric, moleskin, or plastic. Applied to skin to provide prolonged contact, protection or mechanical support at the site of application. Unmedicated plasters provide protection or mechanical support at the site of application. Example: Salicylic acid plaster used on the toes for the removal of corns. The horny layers of skin are removed by the keratolytic action of salicylic acid (concentration ranges from 10% to 40%).  Glycerogelatins Objective 14 Plastic masses containing gelatin (15%), glycerin (40%), water (35%), and an added medicinal substance (10%), such as zinc oxide. Melted before application, cooled slightly and applied to the affected area with a fine brush. Following application, the glycerogelatin hardens, is usually covered with a bandage, and allowed to remain in place for weeks. Official glycerogelatin is zinc gelatin, used in the treatment of varicose ulcers. Also known as zinc gelatin boot because of its ability to form a pressure bandage.  Objective 15 Semisolid dosage form – In class activity, discussion and practice questions A. Differentiate between a. ointments b. pastes c. creams d. gels B. Compare between four types of bases – let’s consider absorption bases in 2 types because of specific quantity of addition of water into it- NOW 5 types of bases C. Discuss different ‘terms’  Objective 15 Differentiate between ointments, pastes, creams and gels Ointment – Oleaginous, varieties based on different types of base composition Paste – Thick, Stiff. More solid, to add viscosity stiffeners are blended into it. Stiffeners are high melting point Creams - Opaque, soft solids or thick liquids Gels - gelling agent, dispersions of small inorganic particles  Practice Q - 7 Pastes are stiffer than ointments and this increased stiffness reduced the percutaneous absorption potential. Therefore, they are typically not used for absorption potential. A.True B.False  Objective 15 Compare and contrast between bases Oleaginous Absorption Water/Oil Oil/Water Water-miscible Ointment Ointment Bases Emulsion Emulsion Ointment Bases Bases Ointment Bases Ointment Bases Composition oleaginous oleaginous base + oleaginous base + oleaginous base + Polyethylene compounds w/o surfactant water (< 45% w/w) water (> 45% w/w) Glycols (PEGs) + w/o surfactant + o/w surfactant (HLB 9) Water anhydrous anhydrous hydrous hydrous anhydrous, hydrous Content Affinity for hydrophobic hydrophilic hydrophilic hydrophilic hydrophilic Water Spreadability difficult difficult moderate to easy easy moderate to easy Washability nonwashable nonwashable non- or poorly washable washable washable  Objective 15 Compare and contrast between bases  Objective 15 C. Discuss different ‘Terms’ of Semi-solid dosage forms Practice questions Dermal Vs Trans-dermal Levigating Agent – Examples ?? Pulverization with intervention Geometric dilution Incorporation Vs Fusion [techniques for mixing] Protectants, emollients, occlusive  Practice Q - 8 What is the purpose of a levigating agent? A.To increase solubility of the active ingredient B.To reduce the particle size of the powder C.To increase the surface area of the active ingredient  Practice Q - 9 What is the major disadvantage of the dermal route of administration? A.difficult for patients to use B.preparations can rub off on clothing C.preparations are often messy D.the ability to deliver large amounts of active ingredient is limited  Learning Objectives 1. Enlist types of semisolid dosage form and routes of administration 2. Enlist therapeutic use of semisolid dosage form 3. Explain dermatological preparation – discuss functions of topically applied semi-solids and discuss three examples. 4. Enlist six advantages, and two disadvantages. 5. Discuss properties of semisolid dosage form 6. Understand ointment and its use – medicated and unmedicated ointment 7. Classification of an ointment bases with examples – four types 1. Oleaginous bases 2. Absorption bases (w/o) 3. W/O emulsion base 4. Water removable base/Emulsion bases (o/w) 5. Water soluble or water miscible base 8. Discuss Incorporation of drug in four types ointment bases – Oleaginous, Absorption, Emulsion, Water miscible 9. Describe excipients used in the semisolid preparation  Learning Objectives 10. Two methods of preparation of ointments 11. Two techniques to mix ingredients of ointments Example: A. Incorporation of Solids, B. Fusion 12. Compare and contrast an ophthalmic ointment base and a topical ointment base. 13. Know quality control, storage, packaging, labeling, BUD 14. Describe and define, 1)Creams 2)Gels/Magmas 3)Plasters 4)Pastes 5)Glycerogelatin 15. In class activity – A. Differentiate between ointments, pastes, creams and gels B. Compare between four types of bases C. Discuss different terms