SOLUTIONS

1. SOLUTIONS

2. SOLUTIONS • A solution is a homogenous one-phase system consisting of two or more components. • Solution consists of two phases: - Solvent phase; determine the phase of the solution and usually constitutes the largest proportion of the system, but there are some exceptions e.g. syrup. • Solute phase; dispersed as molecules or ions throughout the solvent i.e. they are said to be dissolved in the solvent.

3. Solutions Gas in gas (air) solid in solid (alloys) liquid in liquid (alcohol in water) Gas in liquid (cokes) solid in liquid (sugar in water) Solutions Well-mixed (uniform) – single phase homogenous transparent cannot be separated by filter do not separate on standing sugar in water

4. Definitions SOLUBILITY - It is the number of parts of solvent (by volume) that will dissolve one part of solute (by weight of a solid or liquid). - It also can be defined as the amount of a solute that passes into solution - A solute will dissolve best in a solvent that has a similar polarity to itself. MISCIBILITY when the two components forming a solution are either both gases, solids or liquids it is more usual to talk in terms of miscibility rather than solubility.

5. Immiscible: two liquids do not mix e.g. alcohol in water miscible: two liquids can mix (in any quantities) Solutions Solvent: greater quantity (water) Solute: smaller quantity (sugar)

6. ADVANTAGES OF SOLUTIONS • Liquids are easier to swallow, and so more acceptable by paediatric and geriatric use. • Faster therapeutic response. • Uniform distribution of drug throughout the preparation, compared to suspension and emulsion. • Reduced irritation to the gastric mucosa, compared to solid dosage forms, due to immediate dilution by gastric contents.

7. DISADVANTAGES OFSOLUTIONS • Bulky, so inconvenient to transport and store • If the container breaks, the whole product is lost. • Poor stability. • Microbial contamination is more likely. • In-accurate dosing. • Difficult to mask the bitter taste of some drugs.

8. Most solutions prepared in the pharmacy are straightforward; others have special problems associated with them. • All require some knowledge of the solubility characteristics of the drug(s) being dissolved (These may be found in Remington's Pharmaceutical Sciences, dispensing textbooks, Merck's Index). • Pharmaceutical solutions can be (1) simple or (2) complex. In addition that one may find multiple solids (drugs, stabilizers, buffers, colors, etc.) mixed with multiple liquids (water, flavors, alcohol, propylene glycol).

9. Solutions are sometimes classified as: • simple solutions • solutions prepared by chemical reaction. • There is no fundamental differences between them, these terms refer to the method required to prepare them. • As an example, salt dissolved in water is a simple solution. • In contrast, one can prepare Calcium Hydroxide solution (sometimes called Lime Water) by adding Calcium Oxide to water. • That which went in is not that which comes out; a chemical reaction has taken place.

10. Strong Iodine Solution U.S.P. (Lugol’s solution) • R/ Iodine 50 gm Potassium iodide 100 gm purified water ad 1000 ml Iodine dissolves in potassium iodide to form the water soluble I3 complex

11. FORMULATION OF SOLUTIONS A. Aqueous solution B. Non aqueous solution

12. AQUEOUS SOLUTION

13. A. Aqueous solution • Water is the most widely used solvent. Advantages • Lack of toxicity • non-expensive • physiological compatibility Disadvantages • Some hydrolysable drugs such as glycosides and esters form unstable solutions when dissolved in water.

14. TYPES OF WATER • 1. Potable Water: Water freshly drawn from the public water supply (main system) and suitable for drinking. • 2. Pharmacopeal Purified Water BP: - Freshly boiled and cooled immediately before use to destroy micro-organism. - Must be used when the presence of salts is undesirable. - Prepared by distillation or deionization.

15. TYPES OF WATER • 3. Water For Injections • Sterilized (pyrogen-free) distilled water used for parenteral solutions. • CO2-free water: For formulation of solutions of some drugs (e.g. aminophylline), it must be free from carbon dioxide. This is obtained by boiling distilled water for 10 minutes, cooled and sealed in their containers and then sterilized.

16. TYPES OF WATER Aromatic waters

17. Aromatic waters • Aromatic waters are saturated solutions of aromatic or volatile substances in water. • They possess an odor similar to the plant or volatile substance from which they are made • Due to their pleasant odor, they used as flavoring or perfuming vehicles in certain pharmaceutical preparations. • Mostly they exert no therapeutic action. • Examples: peppermint water, chloroform water, camphor water,..

18. Concentrated Aromatic Water (Spirits) • These are strong stock solution of aromatic materials in alcohol. • Fresh aromatic water are prepared by dilution of the strong one; 1 part of strong solution to 39 parts of water (freshly boiled and cooled). • On dilution they yield a fine precipitate. In the finally divided form, the precipitated substance is more easily dissolved in water.

19. How to improve aqueous solubility??

20. IMPROVEMENT OF AQUEOUS SOLUBILITY (1) COSOLVENCY • The solubility of poorly soluble drugs can be improved by the addition of water miscible solvent in which the compound is soluble. • Vehicles used in combination to increase the solubility of a drug are called COSOLVENTS. • Most commonly used blends is water/ethanol blend, other suitable solvents are glycerol, propylene glycol.

21. R/ Sodium Chloride 2.0 G. Menthol .100 G. Alcohol 10 mL. Water q.s. ad 30 G. • Sodium chloride is more soluble in water, menthol is more soluble in alcohol. That is the way they should be dissolved, and then the two solutions should be mixed together.

22. IMPROVEMENT OF AQUEOUS SOLUBILITY (2) pH Control: • If the drug is a weak acid or weak base, its solubility in water can be controlled by the pH of the system. (3) Particle size control: • As particle size decrease the drug solubility increased. (4) Chemical modification: • The drug may be chemically modified to produce a water soluble derivative (usually salt form). • Examples; - sodium phosphate salt of hydrocortisone

23. NON-AQUEOUS SOLUTIONS

24. Non-aqueous solutions • If the drug is insoluble (griseofulvin) or unstable (e.g methylpenicillin) in aqueous systems, it is necessary to use alternative systems such as oils, alcohols, liquid paraffin, glycerol…….

25. Non-aqueous solvents • 1. Fixed oil of vegetable origin - such as olive oil, almond oil, castor oil, ….. • They are used mainly in preparation of intramuscular injections e.g. Oily Phenol Injection BP and Calciferol Injection BP, for depot therapy • Some are of suitable taste and odour for oral use as solvent for materials as vitamin A and D. • Oils are unpleasant to use externally, unless in emulsion.

26. Non-aqueous solvents (2) Alcohols • Ethyl alcohol is a widely used solvent, specially for external use due to its rapid evaporation and cooling effect (e.g. paints and liniments). • It can be used orally as cosolvent (e.g. elixirs) • Isopropyl alcohol, has similar properties to ethyl alcohol, but less likely to be abused if taken orally.

27. Non-aqueous solvents (3) Miscellaneous • Glycerol, • dimethylsulfoxide, • liquid paraffin, • propylene glycols, • tinctures.

28. Types of Preparations • Solutions for cutaneous application; Lotion, liniments, paints, collodions • Ear (otic) prepartions: - Simple solution of drugs in either water, glycerol, alcohol/water mixture for local use - Applied as drops, sprays or washes • Eye preparations: These are small-volume sterile liquids to be instilled on to the eyeball for local effect

29. Types of Preparations • Irrigations: - Sterile, large-volume, aqueous solutions for cleansing of body cavities and wounds. • Mouthwashes and gargles: - Aqueous solution for the prevention and treatment of mouth and throat infection can contain antiseptic and analgesic drugs • Nasal products: - pH should be adjusted to 6.8. - Anti-inflammatory and decongestants are commonly used

30. Types of Preparations • Oral liquids: Elixir, linctuses, mixtures and draughts. • Parentral products: Sterile solution for injection or infusion into the body. • Rectal preparations: - Aqueous or oily preparations for cleansing, diagnosis or therapeutic reasons (e.g.ENEMAS)

31. Types of Preparations • Intermediate products: 1-Aromatic water and spirites 2- Extracts, infusion and tinctures: Are concentrated solutions of active principles from animal or vegetable source. 3- Syrups -Are concentrated solution of sucrose to which drug and flavorings are added. e.g. Codiene Phosphate syrup (cough suppressant)

32. RECOMMENDATIONS ON PREPARING SOLUTIONS • 1. Small quantities of highly soluble materials dissolve immediately; solution rate slows down as more and more solute is added and may stop as "saturation"' is reached. • 2. The more rapid the stirring, the more rapidly solution is achieved (because turbulence reduces the width of the '"diffusion layer" around the particles of solute). There are some situations when vigorous stirring is not desirable e.g. foaming agent (as soap), or viscous solution (formation of air bubbles which could take many, many hours to go away.

33. RECOMMENDATIONS ON PREPARING SOLUTIONS • 3. Particle size reduction by grinding in a mortar with a pestle, this is important for "slightly soluble drug“. • 4. Heating usually hastens solution rate--but should be used only when necessary, avoided in volatile materials. • 5. The '"Order of Addition" may be important. Make certain that you are familiar with the solubility characteristics of your solutes and solvents.

34. 6. As a general rule, non-viscous solutions should be filtered. This rule is not followed when the volume is small since significant amounts of the liquid may be retained by the filter paper.

35. SOLUTION