LECTURE 12 (1).pptx

Creams and ointments

1. Lecture # 12 Creams & Ointments Rahat Fatima (Lecturer, DOP, IIUI)

2. References Jannie Watson, Rees J, Smith I. Pharmaceutical Practice . 5th Ed. Churchill Livingstone; 2014. Chapter # 36 (Pg. 337-347)

3. External Preparations (Introduction to Skin) Skin is the largest organ in the body and has three distinct regions. The hypodermis is the innermost and is often called subcutaneous fat. The dermis is the bulk of the thickness of the skin and contains blood vessels, nerve fibers, sweat glands and hair follicles. The outermost region is the epidermis, which is made up of several layers. One of these layers is the Stratum Basale, in which cells divide and as they move towards the surface, they change appearance and function. The outermost layer, the stratum corneum, acts as the skin barrier. It is made up of about 20 layers of dead keratinized cells. The hair follicles and sweat ducts pass through the stratum corneum to reach the surface.

4. Points to Consider Once in the skin, a lipid-soluble drug will tend to accumulate in lipid regions, while more water-soluble drugs will tend to enter the blood capillaries and be removed from the skin. There are also many metabolic enzymes in the skin which can deactivate drugs. Barriers Care to be exercised while Preparaing Effective formulation makes it possible to achieve adequate and reproducible percutaneous absorption, which is close to zero order kinetics. As a consequence, absorption through the skin from toxic materials is possible and so gloves should always be worn when preparing external preparations.

5. Treating Skin Conditions There are an increasing number of drugs that are effective against skin diseases, but drugs are not the only way of treating skin conditions. Creating physiological changes in the skin can also be beneficial. The main change is to control the moisture content of the skin. Normal skin has 10–25% moisture in the stratum corneum. This level may be reduced in, for example, eczema, or increased, as in skin maceration between the toes. By using an occlusive product (that is, an oily product), water leaving the body through the skin will be trapped and the moisture content will increase. These products are called emollients.

6. Treating Skin Conditions An excess of moisture may be removed using an astringent, a hygroscopic material or, to a lesser extent, a dusting powder. Where an oily vehicle is needed, but moisture must not increase, adding solid particles to the vehicle will allow water to escape. Lubrication of sensitive skin is achieved by using finely divided solids, applied either as a powder or, more efficiently, as a suspension. Cooling the skin relieves inflammation and eases discomfort. It is achieved by evaporating a solvent, usually water or a water and alcohol mixture. Volatile solvents sprayed on the skin give intense cooling.

7. Types of Skin Preparations

8. Solids Dusting powders are applied to the skin for a surface effect such as drying or lubricating, or an antibacterial action. They are made of a fine-particle-size powder, which may be a drug alone or together with excipients.

9. Soaks have an active ingredient dissolved in an aqueous solvent and are often used as astringents, for cooling or to leave a film of solid on the skin. Oily vehicles can be used in bath additives to leave an emollient film on the skin surface. Liquids

10. Lotions are aqueous solutions, suspensions or emulsions that cool inflamed skin and deposit a protective layer of solid. Liniments are alcoholic or oily solutions or emulsions designed to be rubbed into the skin. The medicament is usually a rubefacient. Applications are solutions or emulsions that frequently contain parasiticides. Paints and tinctures are concentrated aqueous or alcoholic antimicrobial solutions. Collodions are organic solvents containing a polymer and drug. There are also many other liquid products including shampoos and foot washes .

11. Semi-Solids Ointments are usually oily vehicles that may contain a surfactant to allow them to be washed off easily (barrier creams). They are used as emollients, or for drug delivery either to the surface or for deeper penetration.

12. Creams & Ointments

13. Creams are traditionally oil-in-water (o/w) emulsions while oily creams are water-in-oil (w/o) emulsions. However, there are also ‘creams’ that are not emulsions. Emulsified creams usually give cooling, are less greasy than ointments and can be used for drug delivery onto or into the skin. They require antimicrobial preservatives. Creams

14. Pastes are vehicles (aqueous or oily) with a high concentration of added solid. This makes them thick so they do not spread and so localizes drug delivery (e.g. Dithranol in Lassar’s Paste). They can also be used for sun blocks. Gels are usually aqueous gels used for lubrication or applying a drug to the skin. Oily gels are also available where occlusion is required. Pastes & Gels

15. These include water, alcohol and the macrogols. Alcohol, usually industrial denatured alcohol, is often added to water to increase the rate of evaporation and produce a more intense cooling effect. The macrogols (polyethylene glycols) are available with a range of molecular weights. Oily Vehicles Ingredients U s ed in Skin Preparations Oils used in external preparations come from one of three sources. Mineral oils (paraffins) are the most widely used. They are complex mixtures of mainly saturated hydrocarbons, which are available in different fractions. Different names are used in different pharmacopoeias Water Miscible Vehicles

16. As chain length increases, so the properties change from liquid, through semi-solid to waxy solid. They have good solvent properties for a wide range of drugs and can be blended to produce intermediate consistencies. They tend to dry the skin, inactivate some antimicrobials, interact with some plastics and can give poor release of drugs. Oily Vehicles Ingredients U s ed in Skin Preparations Light liquid paraffin is not normally used in external medicines. Soft paraffin is the main ingredient in many products, with liquid or hard paraffin being used to thin or thicken them respectively. There are two forms of soft paraffin: yellow and white. Water Miscible Vehicles

17. The latter has been bleached, residues of which may remain. As a general rule, white is used with white or pale colored ingredients, while yellow is used for darker ingredients. The paraffins are occlusive and chemically inert, but do not give good skin penetration. Vegetable oils come from plant sources such as castor, olive, peanut and coconut. The latter two would be rarely used because of severe reactions in patients with nut allergies. Synthetic oils , such as the silicone oils (Dimethicone BP), are used as water repellents and occlusives because they are very hydrophobic. The semi-synthetic isopropyl-myristate is similar to vegetable oil in its properties and use. Oily Vehicles

18. Liquid and semi-solid emulsions, both o/w and w/o, are used externally and require the addition of emulsifying agents. The latter may also be added to an oil without water as in Emulsifying Ointment BP. The presence of a surfactant usually increases the skin penetration of any drug. A wide range of materials can be used as surfactants, either alone or in combinations. Selection is made in view of the type of emulsion required (o/w or w/o) and the charge on the other ingredients (anionic, cationic or non-ionic). Emulsifying Agents

19. Emulsifiers – o/w Emulsifying waxes each contain two ingredients: ceto -stearyl alcohol and a surface-active agent. All three bases are waxy solids that mix with oily materials. Addition of water produces an o/w emulsion –a cream. Both the nonaqueous blends and the creams are easily washed off the skin. Varying the amount of bodying agent, usually ceto -stearyl alcohol, can control consistency. The ratio of oil to water will also alter the consistency of a cream. Emulsifying Agents Hypoallergenic commercial wool fat is a complex mixture of fatty acid esters of cholesterol and other sterols and alcohols. Wool alcohol, a solid, is richer in cholesterol and lanosterol and has fewer impurities. Both it and wool fat increase the ‘water-holding’ capacity of greasy bases. Hydrous wool fat is 7 parts wool fat and 3 parts water and is a softer material. Beeswax is a traditional w/o emulsifier which is occasionally used. Emulsifiers – w/o

20. Calcium soaps and soft soap have traditionally been used to make o/w emulsions. Synthetic surface-active agents are used particularly in commercial products. Low HLB (hydrophilic–lipophilic balance) materials will produce w/o emulsions, while higher HLB surfactants give o/w emulsions. Other Emulsifying Agents

21. SemiSolid Preparation Methodology

22. Semi-Solid Preparation Mixing By Fusion The compounding of many semi-solid preparations includes the blending together of oily materials, some of which are solids at room temperature. The process called ‘mixing by fusion’ achieves this. As the name implies, it involves melting the ingredients together. The process is carried out in an evaporating basin on a water bath or hot plate. It should be noted that a high temperature is not required so 60–70°C is usually adequate.

23. Waxy solids should be grated before weighing and should be added first, so that melting can start while other ingredients are being measured. When all the ingredients are melted, remove the basin from the water bath and gently stir until cold. Mixing, which should be gentle to avoid air bubbles, is necessary to avoid lumps forming. This could happen because the higher melting point ingredients in the eutectic system may precipitate out. Mixing By Fusion (Continued…)

24. Any medicament may be added at different stages of preparation depending on its properties. If soluble and stable, it can be added when the base is molten. If it is less stable, or insoluble but easy to disperse, it can be added during cooling. However, if it is unstable or if dispersion is difficult, it should be added when cold using mixing by trituration. When evaporating basins are being used, recovery of all the product is not possible. Thus, in order to be able to pack the prescribed amount, it is necessary to make an excess of about 10%. Mixing by Fusion (Cont..)

25. Insoluble solids or liquids are incorporated into bases using the technique called ‘mixing by trituration’. Any powders should be passed through a 180 μm sieve before weighing to avoid grittiness in the finished product. Mixing by trituration is carried out on an ointment slab or tile, which may be made of glass or glazed porcelain. A flexible spatula is used to work the materials together. Mixing by Trituration

26. Powders are placed on the tile and incorporated into the base using ‘doubling-up’ as it is worked in. However, it is usually necessary to have two to three times the volume of base to powder, otherwise it will ‘crumble’. Liquids, if present, are usually present in small amounts. To incorporate a liquid, a portion of the base is placed on the slab and a recess made to hold the liquid which is then worked in gently. Mixing By Trituration (Continued…)

27. Mixing by Trituration (Continued…) Larger quantities of liquid should be added a little at a time using the same method. In theory it is possible to recover all material from the slab, but it is normal to allow up to 10% excess for losses. These processes can be carried out in a mortar with a flat base using a pestle with a flat head. However, because recovery of the product is difficult, this is usually reserved for larger-scale batches.

28. Creams are emulsified preparations containing water. They are susceptible to microorganisms which may cause spoilage of the cream or disease in the patient. While preservatives are included, they are usually inadequate to cope with a heavy microbial contamination and growth so the possibility of microbial contamination during preparation should be minimized. Ideally aseptic techniques should be used, but this is not normally possible in extemporaneous dispensing and so thorough cleanliness is employed. Creams

29. Creams As a minimum, all apparatus and final containers should be thoroughly cleaned and rinsed with freshly boiled and cooled purified water, then dried just prior to use. Swabbing of working surfaces, spatulas and other equipment with ethanol will also reduce the possibility of microbial contamination.

30. Method of Preparation

31. Method of Preparation The basic method of making an emulsified cream is to warm both the oily phase and aqueous phase separately to a temperature of about 60°C, mix the phases and stir until cold. It is important that the temperatures of the two phases are within a few degrees of each other and it is advisable to use a thermometer to check this. Rapid cooling will cause the separation of high melting point materials, and excessive aeration as a result of vigorous stirring will produce a granular appearance in the product. Medicaments may, if they are stable, be dissolved in the appropriate phase before emulsification, or can be added by trituration when cold.

32. Dilution of Creams It is sometimes necessary to prepare a dilution of a commercially produced cream, although the practice is undesirable. Choice of diluent is crucial, since the diluent may impair the preservative system in the cream, may affect the bioavailability of the medicament, or be incompatible with other ingredients. The process of dilution also increases the risk of microbial contamination. Thus, dilutions should only be made with the diluent(s) specified in the manufacturer’s data sheet and heat must be avoided. All diluted creams should be freshly prepared and be given a 2-week shelf-life.

33. Practical Examples

34. Prepare 50g of Simple Ointment This is a simple blend of solid and semi-solid oily ingredients made by fusion. Yellow or white soft paraffin is chosen according to the color of the finished product. In this case, since there is nothing else to be added, white soft paraffin should be used; 60 g is made to allow 50 g to be dispensed.

35. Grate the hard paraffin and cetostearyl alcohol. Weigh 3 g of each and place in an evaporating basin on a water bath or hot plate. Weigh the wool fat, using a piece of paper to allow full recovery of the material, and add it to the evaporating basin, followed by the soft paraffin (also weighed on paper). Stir gently until fully melted. Remove from the heat and continue to stir gently until cold. Weigh 50 g of base into a tared ointment jar. If an ointment jar is used, a greaseproof paper disc should be placed on the surface of the ointment to protect the liner of the lid from the greasiness. Method of Preparation

36. Shelf-Life & Storage Store in a cool place. An expiry date of 4 weeks is appropriate.

37. Formulation notes . The BP directs that the simple ointment be prepared with white soft paraffin. If simple ointment is available, the trituration can be carried out on a slab and all the product recovered. However, if simple ointment is also being made, 50 g should be adequate to ensure that 45 g are available. Precipitated sulfur, while of smaller particle size than sublimed sulphur , can give a gritty feel unless it is passed through a 180 μ m sieve.

38. Sieve and then weigh out the precipitated sulfur and place it on the slab. Weigh out the simple ointment (using a piece of paper to prevent it sticking to the balance), and place it on a different part of the slab. Take a portion of the sulfur and a portion of the base of about three times the volume of the sulfur and work them together vigorously until there is no sign of any particles of sulfur. Spreading a thin layer on the slab helps check this. Gradually add the remaining sulfur and base. Collect the ointment together on the slab using the spatula and pack 50 g. Method of Preparation

39. Shelf-Life & Storage Store in a cool place. An expiry date of 4 weeks is appropriate.