Pharmaceutical Ointments and Pastes Lecture Notes PDF

‫رلبلنللا م هللا مسب‬ Pharmaceutical Ointments and Pastes Deina Elraiah Mohamed El Hassan Master degree of Pharmaceutical Technology (University of Gezira) PhD holder of Pharmaceutical Technology (Karary University)  ??????????????? Define semi solid...

‫رلبلنللا م هللا مسب‬ Pharmaceutical Ointments and Pastes Deina Elraiah Mohamed El Hassan Master degree of Pharmaceutical Technology (University of Gezira) PhD holder of Pharmaceutical Technology (Karary University)  ??????????????? Define semi solid dosageform? What is main advantages and disadvantages of semisolid preparations? Mention the ideal properties of semisolid preparations? what is ingrideients needed for semisolid? Define creams with mention all the types of it?  Definitions Pharmaceutical ointments : Are greasy or oily semisolid systems that are applied externally, primarily to the skin and also to mucous membranes, e.g. the rectum, the vagina and the eye. Typically, medicated ointments are used for the treatment of Infection and inflammation.  However, non-medicated ointments are commonly used due to their emollient/lubricating properties. Pharmaceutical Pastes: Pastes are semisolid dosage forms that contain a large proportion of solid component. They differ from ointments in their consistency, and consequently are thicker and stiffer. Pastes can be made either of fatty bases, such as petrolatum and hydrophilic petrolatum, or of aqueous gels, such as celluloses. Pastes may contain one or more drug substances intended for topical application.  Pastes are well adsorbed on the skin and can be easily removed from skin. Pastes that contain hydrophobic components can be water impermeable and prevent dehydration. Examples of pastes include the commonly used tooth-pastes and zinc oxide paste. Toothpaste contains an abrasive solid for cleansing purposes and sometimes also includes a fluoride salt.  Pharmaceutical pastes are generally composed of ointment bases that contain a high concentration (frequently >50% w/w) of dispersed drug. The viscosity of pharmaceutical pastes is greater than that of pharmaceutical ointments. According to the British Pharmacopoeia (BP): Ointments are formulated to provide preparations that are immiscible, miscible or emulsifiable with the skin secretion. 1. Hydrophobic ointments and water-emulsifying ointments are intended to be applied to the skin or certain mucous membranes for emollient, protective, therapeutic or prophylactic purposes where a degree of occlusion is desired. 2. Hydrophilic ointments are miscible with the skin secretion and are less emollient as a consequence. Ø The formulation of ointments and pastes involves the dispersal or dissolution of the selected therapeutic agent into an ointment base and, therefore, in addition to Ø Physical properties of the dispersed/dissolved drug, Ø Physicochemical properties of the ointment base are fundamental to the clinical and non-clinical performance of this type of dosage form. The choice of ointment base is dependent on several factors, including: (1) The site of application. (2) The required rate of drug release. (3) The chemical stability of the drug. (4) The effect of the therapeutic agent on formulation viscosity.  Types of ointments 1. Dermatological ointments 2. Ophthalmic ointments 3. Rectal ointments 4. Vaginal ointments 5. Nasal ointments Types of base for ointments and pastes There are four types of base that are used to formulate pharmaceutical ointments and pastes: (1) Hydrocarbon or oleaginous bases (2)Absorption bases (3) Water-miscible/removable bases (4) Water-soluble bases (1) Hydrocarbon bases: Hydrocarbon bases are non-aqueous formulations, based on various paraffins, that have the following properties: 1. Emollient, thereby restricting water loss from the site of application due to the formation of an occlusive film. 2. Excellent retention on the skin 3. Predominantly hydrophobic, and therefore difficult to remove from the skin by washing and difficult to apply to (spread over) wet surfaces 4. Only a low concentration of water (< 5%) may be incorporated into hydrocarbon bases (with careful mixing) 5. Chemically inert. 6. Provide optimum stability for medicaments such as antibiotics. Hydrocarbon bases frequently contain the following components: a) Hard paraffin. b) White/yellow soft paraffin. c) Liquid paraffin(mineral oil). d) Microcrystalline wax.  (a) Hard paraffin This is a mixture of solid saturated hydrocarbons that are derived from petroleum or shale oil. Hard paraffin is a colourless or white wax-like material that is physically composed of a mixture of microcrystals. The meltiparaffin is between 47 and 65 C and, when solid, it is used to enhance the rheological properties of ointment bases. (b) White/yellow soft paraffin This is a purified mixture of semisolid hydrocarbons that are derived from petroleum. White/yellow soft paraffin consists of microcrystals embedded in a gel composed of liquid and amorphous hydrocarbons.  The melting range of soft paraffins is between 38 and 60 C. White soft paraffin and yellow soft paraffin may be used as an ointment base without the need for additional components, although it may be combined with liquid paraffin. (c ) Liquid paraffin (mineral oil) This is a mixture of saturated aliphatic (C 14 –C 18 ) and cyclic hydrocarbons that have been refined from petroleum. It is usually formulated with white/yellow soft paraffin to achieve the required viscosity for application to the required site. Formulations containing liquid paraffin require the incorporation of an antioxidant due to the ability of this material to undergo oxidation. (d) Microcrystalline wax This is a solid mixture of saturated alkanes (both linear and branched) with a defined range of carbon chain lengths. This excipient is used to enhance the viscosity of ointments and creams. One of the advantages of microcrystalline wax is the greater physical stability provided to formulations containing liquid paraffin (reduced bleeding of the liquid component). (2) Absorption bases Unlike hydrocarbon bases, absorption bases may be formulated to contain significant amounts of an aqueous phase. These may be either non-aqueous formulations to which an aqueous phase may be added to produce a water in oil emulsion (termed non-emulsified bases) or water in oil emulsions that can facilitate the incorporation of an aqueous phase (without phase inversion or cracking). Although absorption bases can contain a larger volume of aqueous phase than hydrophobic bases, they are still difficult to remove from the site of application by washing. This is due to the hydrophobic properties of this formulation class. Non-emulsified bases (anhydrous) These are hydrophobic formulations to which water may be added. It absorbed water but not water removable. Following application, a film is formed that offers occlusion (and hence emollient properties). The spreading properties of these formulations are more favorable than for hydrocarbon bases.  Typically non-emulsified bases are commonly composed of: (1)One or more paraffins (2) A sterol-based emulsifying agent. Examples of the types of emulsifying agents used in absorption bases include: (1)lanolin (wool fat). (2) Lanolin alcohols (wool alcohols). (3) Bees wax (white or yellow). A. Lanolin (wool fat) Lanolin is a wax-like material that is derived from sheep’s wool. It is available in two forms, termed Ø lanolin (wool fat) and Ø hydrous lanolin (wool alcohols). Lanolin is typically mixed with vegetable oils or paraffins to produce an ointment base. The usual concentrations of lanolin used in ointments (e.g. Simple Ointment BP) range from 5 to 10% w/w. B. Lanolin alcohols (wool alcohols) Wool alcohol is a crude mixture of sterols and triterpene alcohols and contains at least 30% cholesterol and 10–13% isocholesterol. This is added to mixtures of paraffins (hard, so white/yellow soft or liquid) to produce the required consistency. The inclusion of wool alcohols (5% w/w) results in a 300% increase in the concentration of water that may be incorporated into paraffin bases. Wool Alcohols Ointment BP C. Beeswax (white or yellow) Beeswax is a wax that consists of esters of aliphatic alcohols and linear aliphatic fatty acids that is combined with paraffins to produce non-emulsified bases. White beeswax is the bleached form of yellow beeswax. Water in oil emulsions (hydrous) Ointment bases in this category can contain a greater concentration of water but yet can still provide similar performance to that provided by non-emulsified bases e.g. occlusion, spreading properties. A common excipient that is employed in the formulation of this type of ointment base is hydrous lanolin (Hydrous Wool Fat BP) The water content of bases that have been formulated using hydrous lanolin is significant, e.g. Oily Cream BP is a water in oil emulsion ointment base that is composed of wool alcohols (50% w/w) and water (50% w/w). (Hydrous Ointment BP) Absorption bases, either hydrous or anhydrous, are seldom used as vehicles for commercial drug products. (3) Water-miscible/removable bases(Emulsifying bases) These are anhydrous bases that contain sufficient emulsifying agent (oil in water) to make them miscible with water and therefore ‘washable’ for topical applications. The use of these bases offers a number of advantages: 1. They are able to contain large volumes of water, e.g. aqueous solutions of drug, excess moisture at the site of Application. 2.They are not occlusive. 3.They may be easily washed from the skin and from clothing. Furthermore, they may be readily applied to (and removed from) hair. The British Pharmacopoeia describes three water-miscible/ removable bases: 1. Emulsifying ointment 2. Cetrimide emulsifying ointment 3. Cetomacrogol emulsifying ointment. Each of these contains: liquid paraffin 20% w/w white soft paraffin 50% w/w anionic, cationic or non-ionic emulsifying wax 30% w/w. As may be observed, an important component of this ointment base is emulsifying wax, of which there are three types: (1)anionic; (2) non-ionic; and (3) cationic. The important properties of these waxes are as follows: Anionic emulsifying wax(Emulsifying Ointment BP ) This is a waxy solid that, when incorporated into a paraffin base, may be used to produce an oil in water emulsion, e.g. Aqueous Cream BP (which contains 10% w/w anionic emulsifying wax). Anionic emulsifying wax is composed of: Ø Cetostearyl alcohol 90 g Ø Sodium lauryl sulphate 10 g Ø Purified water 4 ml. Non-ionic emulsifying wax This is also referred to as Cetomacrogol Emulsifying Wax BP and is composed of: Ø cetostearyl alcohol 800 g Ø cetomacrogol 1000 (macrogol cetostearyl ether 22) 200 g. Cationic emulsifying wax This is also referred to as Cetrimide Emulsifying Wax BP. Cationic Emulsifying Wax BP is composed of: Ø cetostearyl alcohol 900 g Ø cetrimide 100 g. (4) Water-soluble bases. In contrast, water-soluble bases are composed entirely of water-soluble ingredients. The advantages of the use of these bases include: 1.They are non-greasy and may be easily removed by washing. 2.They are miscible with exudates from inflamed sites. 3.They are generally compatible with the majority of therapeutic agents.  Water-soluble bases are predominantly prepared using mixtures of different molecular weights of polyethylene glycol to produce the required ointment consistency. Lower average molecular weights of this polymer are liquids. As the average molecular weight increases, the consistency of this polymer changes from a liquid to a waxy solid Blends of 60% w/w polyethylene glycol 400 (a liquid) and 40% w/w polyethylene glycol 4000 (a solid) have been used as a water- soluble ointment base. The main disadvantage associated with water-soluble bases is their inability to incorporate large volumes of aqueous solutions. Therefore the use of these bases is usually reserved for the incorporation of solid therapeutic agents. Other excipients may be included in ointments and pastes, including: A. Additional/alternative solvents. (1) liquid silicone (2) Vegetable oils. (3) Organic esters. B. Preservatives. C. Antioxidants (1) Lipophilic antioxidants (2) Hydrophilic antioxidants  Selection of bases Based on : 1. Desired release rate 2. Advisability of occlusion 3. Short term or long term stability 4. Influence of drug consistency of ointment base. 5. Patient factor :dry or weeping skin