1. PHYSICOCHEMICAL PRINCIPLES Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics Faculty of Pharmacy Omer Al-Mukhtar University Tobruk, Libya. E-mail: nanjwadebk@gmail.com 2014/06/031 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

2. CONTENTS Introduction to expressions of concentration Calculations involving expressions of concentration Equivalent weight Milli-equivalent Tonicity (osmosis, methods of adjusting) Buffers (systems, drugs as buffers and applications) References 2014/06/032 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

3. Introduction to expressions of concentration May different ways of expressing concentration are used and pharmacists should be familiar with them and how to convert one to another. Sometimes prescripts are written using a mixture of different expressions of concentration, so the pharmacist must be familiar with these and be able to convert them so that a consistent method of expressing concentration is used. Perhaps the simplest expressions of concentration are as a fraction (for example1/4), and as a decimal expression (for example 0.25). 2014/06/033 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

4. Calculations involving in expressions of concentration 1. Ratios and percentages Percentage weight in weight (w/w) Percentage weight in volume (w/v) Percentage volume in volume (v/v) Miscellaneous examples 2. Parts Concentrated waters 3. Molar and Equivalent solutions Molarity Molality Mole fraction 2014/06/034 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

5. 1. Ratios and percentages A ratio is the relative magnitude of two like quantities. Thus: 1:10= 1 part in 10 parts, Which might be 1 g in 10 g or 1 mL in 10 mL. Therefore, if 1 g of sucrose is in 10 g of solution, the ratio is 1:10. Equally, if we have 10 g of sucrose in 100 g of solution the ratio remains 1:10. A percentage is the number of parts per one hundred and is probably the commonest expression of concentration used in pharmacy. Returning to the example of sucrose above we can express 10 g sucrose in 100 g of solution as 10%. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 5

6. Percentage weight in weight (w/w) A percentage weight in weight (% w/w) is the number of grams of an active ingredient in 100 grams of a mixture. It should be noted that the ingredients in this mixture could be a solid or liquid, but for the latter, its quantity would be measured by weight not volume. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 6

7. Percentage weight in volume (w/v) A percentage weight in volume (% w/v) is the number of grams of an active ingredients in 100 mL of liquid. Again the smaller quantity could be solid or liquid, measured by weight, but the final mixture must be a liquid since a volume is being measured. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 7

8. Percentage volume in volume (v/v) A percentage volume in volume (% v/v) indicates the volume of an active ingredient in 100 mL of a liquid. In this case both ingredients must be liquids since both are to be measured by volume. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 8

9. Miscellaneous examples Sometimes a percentage is specified but no indication given as to whether it is weight in weight, weight in volume or volume in volume. In most situations it is assumed that solids in liquids are percentage weight in volume and liquid in liquids are percentage volume in volume. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 9

10. 2. Parts When active ingredients are included in equal amounts, or simple ratios, rather than using percentages the prescriber may indicate the quantities in parts. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 10

11. Concentrated waters Liquid preparations for oral use are often flavoured to make them more palatable for the patient. In extemporaneously prepared products the flavouring is frequently a flavoured water, e.g. peppermint water, anise water. These flavoured waters are available in a concentrated form and are either used as such, or are diluted to provide the vehicle for the preparation. All concentrated waters have the same dilution factor, i.e. 1part of concentrated plus 39 parts of water to give 40 parts of flavoured water. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 11

12. 3. Molar and Equivalent solutions Moles and equivalents are expressions of quantity. Therefore, they can become part of an expression of a concentration in a mixture. In pharmacy this is always in a volume, normally expressed as mmol/mL, mmol/L,  mol/L or mEq/L. A 1 molar solution contains 1 mole of material dissolved in 1 litre. Starting point it is possible to calculate the amount of material required for different volumes of different strengths of solution. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 12

13. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 13 Molarity

14. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 14 Molarity

15. Molality 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 15

16. Normality 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 16

17. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 17 Mole fraction

18. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 18 Mole fraction

19. Milli-equivalent (mEq) The concentrations of solutes in body fluids and in solutions used as replacements for those fluids are usually expressed in terms of the number of millimoles (1 millimole = one thousandth of a mole) in a litre of solutions. 2014/06/0319 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. mEq= molecular weight (expressed in milligrams) Valence (equivalent weight)

20. Equivalent weight The weight of the substance which combines with 1 gram of hydrogen or 8 grams of oxygen is called as equivalent weight. Equivalent weight is the weight of the substance which loses or gains 1mole of electrons. 2014/06/0320 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. Equivalent weight = molecular weight (expressed in milligrams) valence (equivalent weight)

21. Formality 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 21

22. Tonicity ( Osmosis, Methods of adjusting) Tonicity: Tonicity are characteristics of parenteral preparations. It is important that they be adjusted to be as close as possible to the values for human blood, to prevent damage to blood cells and organs. Osmosis: The osmotic pressure of a solution is the external pressure that must be applied to the solution in order to prevent it being diluted by the entry of solvent via a process known as osmosis. 2014/06/0322 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

23. Tonicity (methods of adjusting) 1.Freezing point depression: The freezing point depression of blood plasma and tears is 0.52 0 C. Thus solutions that freeze at -0.52 0 C have the same osmotic pressure as body fluids. Hypotonic solutions have a smaller freezing point depression and require the addition of a solute to depress the freezing point to - 0.52 0 C 2.Some methods of calculating for isotonicity Sodium chloride equivalents Molar concentrations Serum osmolarity 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 23

24. Making solutions isotonic An isotonic solution is a solution in which body cells can be bathed without a net flow of water across a semipermeable membrane – 0.9% normal saline (NS) Injection solutions are often made isotonic with 0.9% w/v sodium chloride solution. The amount of solute, or the required dilution necessary to make a solution isotonic, can be determined by a number of different methods. 2014/06/03 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 24

25. Buffers (systems, drugs as buffers and applications) Buffer are materials which, when dissolved in a solvent, will enable the solution to resist any change in pH should an acid or an alkali be added. The choice of suitable buffer depends on the pH and buffering capacity required. It must be compatible with other excipients and have a low toxicity. Most pharmaceutically acceptable buffering systems are based on carbonates, citrates, gluconates, lactates, phosphates or tartrates. Borates can be used for external application, but not to mucous membranes or to abraded skin. 2014/06/0325 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

26. THANK YOU e-mail: nanjwadebk@gmail.com 2014/06/0326 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.