Liquid oral solutions solubility

Oral dosage forms available for administration to animals include oral solutions, liquids, suspensions, gels, pastes, capsules, tablets, ruminal boluses, powders and granules for addition to feed, soluble powders for... 

In France, it is the custom before a meal to partake of an aperitif, usually an aniseed-flavoured spirit called pastis. Pastis (e.g. Ricard , Pernod ) when it comes out of the bottle is a clear, light brown coloured solution of volatile oils from the seeds of the anise plant (Pimpinella anisum), which impart the characteristic aniseed flavour to the drink, dissolved in approximately 40% v/v ethanol. When a pastis is drunk, it is mixed with water and ice, whereupon the liquid becomes cloudy. This happens because the anise oils are hydrophobic, non-polar liquids and not very water-soluble. They are only held in solution by the high alcohol content of the drink. When the alcohol is diluted with water, the oils come out of solution and form an emulsion of oil droplets in the aqueous phase. This is what gives the drink its cloudy appearance. Oral solutions of anise oils have been used pharmaceutically for their carminative action and as an aid to digestion for many years, although it seems to this author preferable to consume anise oils in the form of a pastis, rather than in the form of a bottle of medicine. 

The main choice will be between an oral solution and an oral suspension. For some active substances an emulsion or solubilisate is the appropriate form. However in some cases (e.g. because of an intermediate solubility of the active substance) the pharmacist will have no other option than to dispense an oral solid dosage form and instruct the patient how to manipulate it safely (see Sect. 37.6.2). Proper consideration of the options may prevent formulation mistakes with probably severe consequences. This especially applies to the unreflected use of suspending bases for rendering an oral solid into an oral liquid. 

The pH of an oral liquid is important for the flavour, solubility and stability of the active substance and for preservation. The preferred pH for an oral solution is between 5.5 and 7.5. A pH < 5.5 often tastes better, but may degrade the tooth enamel although the total amount of free acid plays a role as well [30]. A pH above 8 often gives an unpleasant taste. 

PEG is an amphiphilic polymer that is soluble in both aqueous and organic solvents. In addition it has a low level of cellular and protein absorption and is therefore grafted to surfaces of medical devices to prevent deposition of proteinaceous material or bacterial surface growth. It is also conjugated to proteins and to colloidal dosage forms, e.g., liposomes, to minimise their recognition by the immune system. Furthermore, PEG have been widely reported to increase the solubility of poorly soluble therapeutic agents when formulated as liquid formulations, e.g., oral solutions, injections, and as solid dispersions (a.32). 

The physical form of a material destined for oral administration often presents unique challenges. Liquids can be administered as supplied or diluted with an appropriate vehicle, and powders or particulates can often be dissolved or suspended in an appropriate vehicle. However, selection of an appropriate vehicle is often difficult. Water and oil (such as the vegetable oils) are used most commonly. Materials that are not readily soluble in either water or oil can frequently be suspended in a 1% aqueous mixture of methylcellulose. Occasionally, a more concentrated methylcellulose suspension (up to 5%) may be necessary. Materials for which appropriate solutions or suspensions cannot be prepared using one of these three vehicles often present major difficulties. 

Polyoxyl 35 castor oil is mainly used as an emulsifing and solubilizing agent, and is particularly suitable for the production of aqueous liquid preparations containing volatile oils, fat-soluble vitamins, and other hydrophobic substances. Cremophor EL emulsifies or solubilizes the fat-soluble vitamins A, D, E, and K in aqueous solutions for oral and topical administration. In 1 mL of a 25% v/v aqueous polyoxyl 35 castor oil (Cremophor EL) solution it is possible to incorporate approximately 10 mg of vitamin A palmitate approximately 10 mg of vitamin D approximately 120 mg of vitamin E acetate or approximately 120 mg of vitamin Kj. 

Tripelennamlne Gtrate, USP. The oily free ba.se of iripelcnnaminc citrate, 2- benzyl 2-(dimethylamino)etliyl -jminolpyridine citrate (1 1). PBZ (Pyribenzamine Citrate), ii available as the less bitter nuin(M.-itrute salt, which is a while aystallinc powder freely soluble in water and in alcohol. A 1% solution has a pH of 4.2.S. For oral administration in liquid dose forms, the citrate salt is less biller and thus mote palatable than the hydrochloride. Because of the differ-mce in molecular weights, the doses of the two salts must he equaled—30 mg of the citrate salt is equivalent to 20 mg of the hydrochloride salt. 

Liquid formulations account for about 30% of products in the UK market and, because they are easy to swallow, are favoured for paediatric and geriatric use. An aqueous solution is the simplest formulation to produce, but more complex suspensions or emulsion systems will be required if the drug is poorly soluble. Liquid formulations can be administered by all routes and are probably the most versatile systems. Liquids are, however, bulky, difficult to transport and container breakage can result in catastrophic loss. The ultimate aim is to provide the desired dose in a suitable liquid volume which, for oral products, is 5 ml. 

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