Formulation and Manufacturing Considerations of Elixirs: The USP XVII defines elixirs as clear, sweetened hydro alcohol liquids intended for oral use containing flavoring substances or active medicinal agents. Their primary solvents are alcohol and water, with glycerin, sorbitol, and syrup sometimes as an additional solvent and/or sweetening agents. They are prepared by a simple solution or a mixture of several ingredients. They are used either as vehicles or for the therapeutic effect of the medicinal substances that they contain.
Main Ingredients: Alcohol, Water, Glycerin, Preservatives, Sorbital, Flavouring agents.
Types of Elixirs: Medicated Elixirs and Non-medicated Elixirs. Simple, no therapeutic agents υ May only contain alcohol, sweetening agents, coloring agents υ Self-preserve Uses: υ They are used purely as diluting agents υ solvents for drugs [containing approximately 25 percent alcohol, e.g., simple elixir, Iso-alcoholic elixir or low alcohol elixir (containing 8-10% alcohol), High alcoholic elixir (containing 75-78% alcohol)] Example Aromatic elixir, Isoalcoholic Elixir
Formulation of Elixirs
Generally, elixirs contain the following ingredients:
1. Vehicles: About 10-20% of alcohol is used for keeping oils, vegetable extracts, tannins, etc in solution form. Glycerol and propylene glycol are used as a solvent.
2. Stabilizers: In neomycin elixir, citric acid is used to adjust pH 4.0 to 5.0 to minimize the darkening that occurs on storage. Disodium edetate should be used to sequester heavy metals that catalyze the decomposition of antibiotics.
3. Flavouring agents: Sweetening agents and fruit flavors are used in medicinal preparation. e. g. (i) Black currant syrup in chloral Elixir, (ii) Compound orange spirits with glycerol in phenobarbital elixir.
4. Preservatives: In elixir, fermentation and mold growth are inhibited when it contains more than 20% of alcohol, propylene glycol, or glycerol. The commonly used preservatives are double strength chloroform, spirit, and benzoic acid, and methyl ester of p- hydroxybenzoic acid.
Method of Preparation
Dissolve the water-soluble ingredients in part of the water, add and dissolve the sucrose in it. Dissolve the other ingredients in the alcohol. (Concentration of alcohol should be 5- 40% to make clear solution) The aqueous solution is then added to the alcoholic solution with constant stirring and makes up the volume with the solvent or vehicle specified in the formulation. Sucrose increases viscosity but decreases the solubility properties of water and so must be added after the primary solution has been carried out. The high alcoholic content is maintained during preparation by adding an aqueous phase to the alcoholic solution. Elixirs should be brilliantly clear and therefore strained or filtered, if necessary, subjected to clarifying action of purified talc or siliceous earth.
Dry Elixirs: Dry elixirs containing a non-steroidal anti-inflammatory drug and ethanol were encapsulated in dextrin. The dissolution rate constant of the drug from the microcapsules usually increased considerably compared to the drug alone, possibly due to the cosolvent ethanol.
Manufacturing Considerations
1. Raw Materials: The raw materials used in the manufacturing of liquids should conform to well thought out specifications. These specifications should assure identity, purity, uniformity, and freedom from excessive microbial contamination. Incoming raw materials should be impounded and thoroughly tested before they are released for manufacturing.
Aside from the active ingredient water is usually the most important constituent in a liquid product. It should meet the USP requirements for purified water. It may be obtained by distillation or ion exchange treatment. In recent years, manufacturers have devoted considerable effort to upgrading the microbial purity of the water supply used in oral liquids. Techniques employed include reverse osmosis purification, ultraviolet sterilization, membrane filtration, and constant circulation in piping systems that have no “dead ends” where microorganisms can thrive. In general, the most difficult microbes to remove from a purified water system are the Pseudomonas shows a purified water system designed to minimize microbial growth.
2. Equipments:
The equipments used include:
- Mixing tanks: These are usually made up of stainless steel. They are available in different sizes. Sometimes heating and cooling of the solution are necessary during the manufacture of liquid orals. In such cases, tanks are jacketed through which either steam or cold water can be supplied for the purpose. They are facilitated by see-through charging ports and illuminated. With these facilities, the contents inside can be observed.
- Agitators: During mixing the contents must be stirred thoroughly to ensure complete solubility of the contents. The mixing of liquids is easy if they are miscible and mobile. A simple mixing device is essential to encourage the flow of liquids. A high-capacity electric stirrer may be used if the liquids are of high viscosity. Agitating systems fixed to the mixing tanks serve this purpose.
- Measuring devices: Measuring devices of different capacities are required for measuring the liquids.
- Filtration systems: The solvents used are filtered before using them for preparation. Even such systems, sometimes, are used for sterilization of liquids. Though liquid orals are always not necessary to be sterile, liquids are filtered to polish the preparation.
- Bins: The liquids are stored in the bins after filtration for further use.
- Piping: A piping system is required for the transport of the liquids from storage bins to filling equipment. The distance between the storage bin and filling equipment must be as short as possible. Because more the distance more will be the chances of microbial contamination.
All the equipments used must be thoroughly cleaned using a well-validated cleaning procedure. Finally, the equipments must be sterilized. For sterilizing the following agents can be used.
- Dilute solutions of hydrogen peroxide
- Phenol derivatives
- Peracetic acid
- Alcohol
- Boiling water
- Autoclave
- Steam
- Dry heat
3. Personal: One important source of contamination is personal working. To avoid contamination, the person must wear a head covering, gloves, and face masks at all times. In addition, a continuous education program is essential to keep the person aware of the procedure.
4. Compounding Procedure: Dilute solutions, prepared from rapidly dissolving materials, are simply prepared by charging the solute to the solvent and agitating until the solution is homogeneous. When more concentrated solutions are being made, or when the solute is slowly dissolving, it may be advantageous to employ heat.
Compounding Instructions:
- Charge 2000 L of purified water through the water meter into the compounding tank. Check the volume against the outage chart. Heat to approximately 50°C.
- To the water in the compounding tank, charge the following materials in the amounts specified in the batch sheet. Dissolve each one, with agitation, before adding the next (a) drug, (b) sodium benzoate, (c) standard granulated sugar. Agitate the contents of the compounding tank until homogeneous, and then cool to 30°C.
- Charge the specified amount of glycerin to the compounding tank. Agitate until the batch is homogeneous.
- Charge the specified amount of sorbitol solution to the compounding tank. Agitate until the batch is homogeneous.
- Measure 20 L of alcohol into a suitable stainless steel container. Add and dissolve the specified charge of menthol. Add and dissolve the specified charge of flavor.
- Charge the alcoholic solution of menthol and flavor to the batch in the the-compounding tank. Agitate until homogeneous.
- Charge the balance of the specified amount of alcohol to the batch. Agitate until homogeneous.
- Charge 10 L of purified water to a clean stainless steel container. Add to the water and dissolve the specified amount of FD and C Yellow No. 6.
- Charge the dye solution to the batch in the compounding tank, and agitate until homogeneous.
- Add to the compounding tank sufficient purified water to bring the batch volume to 5000 L.
- Weight out 2.5 kg of filter aid, and charge it to the contents of the compounding tank. Agitate for 10 min. The batch is now ready to filter.
- Cycle the batch through the filter and back to the compounding tank until the filtrate is clear. At this point, the filtrate may be discharged and collected in the designated holding tank.
- Sample the batch, and submit it for testing by standard procedure.
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