solubility experimental methods.pptx

solubility: experimental methods

1. Solubility experimental methods Prepared by Dr. Anumalagundam Srikanth Dept. of .Pharmaceutical analysis

2. The solubility of a substance refers to the amount of substance that passes into solution to achieve a saturated solution at constant temperature and pressure . The solvent is generally a liquid, which can be a pure substance or a mixture of two liquids . One may also speak of solid solution, but rarely of solution in a gas . Solubility = Maximum volume/mass of thesolute volume of a solvent

3. One way of measuring solubility is to determine the maximum mass of solute that can be dissolved in 100 ml of solvent at a particular temperature. Solubility should ideally be measured at two temperatures: 4 ° c and 37 ° c. 4 ° c to ensure physical stability. 37 ° c to support biopharmaceutical evaluation. If solubility is <1mg/ml indicates poor absorption, need to improve solubility by preformulation studies.

4. Reasons for Determining Solubility: During recent years, considerable change in the solubility of pharmaceutical R&D compounds and drugs towards lower solubility. Clearly a trend towards higher percentages falling into BCS class II (high permeability, low solubility) and IV (low permeability, low solubility) is observed Solubilites of a drug represent the Bioavailability of the drug. For efficient drug delivery

5. Types of SOLUBILITY Qualitative Solubility: solubility is defined as “ the spontaneous interaction of two or more substances to form a homogenous molecular dispersion ”. Quantitative solubility: it is defined as “ concentration of a solute in saturated solution at a constant temperature”.

6. USP & IP Solubility Criteria Descriptive term Part of solvent required per part of solute Very soluble Less than 1 Freely soluble From 1 to 10 Soluble From 10 to 30 Sparingly soluble From 30 to 100 Slightly soluble From 100 to 1000 Very slightly soluble From 1000 to 10,000 Practically insoluble 10,000 and over

7. Solubility Studies include Intrinsic Solubility o pH solubility Profiling Solubility in Pharmaceutical solvent Effects of Surfactants

8. Intrinsic Solubility Intrinsic solubility is the equilibrium solubility of the free acid or free base form of an ionisable compound at a pH where it is fully un- ionised . Equilibrium solubility is the concentration of compound in a saturated solution when excess solid is present, and solution and solid are at equilibrium.

9. pH Solubility Profiling Changes in pH- Altered the solubility of acidic /basic compounds. The solubility of an acidic or basic drug depends on the pKa of the ionizing functional group and the intrinsic solubilites for both the ionized and un- ionized forms. pH so l u b il i t y pr o file o f a dr u g ca n be e stablis h e d by r u nn i ng the equilibrium solubility experiment within pH range of 3-4.

10. Solubility in Pharmaceutical solvents To enhance the solubility of Pharmaceutical products, add Co-solvents e.g . ethanol, methanol By adding surfactants

11. Effect of Surfactants Surfactants are wetting agents that lower the surface tension of a liquid, allowing easier spreading, and lower the interfacial tension between two liquids types: Ionic Surfactnats : Cationic: e.g. Cetyl Trimethyl Ammonium Bromide , Hexadecyl Trimethyl Ammonium Bromide, and other Alkyltrimethyl Ammonium Salts, Cetylpyridinium Chloride Anionic: e.g. Sodium Dodecyl Sulphate , Ammonium Lauryl Sulphate and other alkyl sulfate salts, Sodium Lauryl Sulphate , also known as Sodium Lauryl Ether Sulphate (SLES). Zwitterionic : e.g. Phospholipids, phosphatidylethanolamine, phosphatidylcholine

12. Solubility Analysis Preformulation solubility studies focus on drug solvent system that could occur during the delivery of drug candidate. For e.g. A drug for oral administration should be examined for solubility in media having isotonic chloride ion concentration and acidic pH.

13. Preformulation solubility Studies Determination of pKa value (Ionization Constant) Temperature dependence pH Solubility profile Solubility products Ksp Solubilization Mechanisms Rate of Dissolution.

14. Determination of Solubilities : The following points should be considered: The solvent & solute must be pure. A saturated solution must be obtained before any solution is removed for analysis. The method of separating a sample of saturated solution from undissolved solute must be satisfactory. The method of analyzing solution must be reliable Temperature must be adequately controlled .

15. Method to determine solubility Shake Flask Method Advantages Most accurate method Accurate for broadest range of solutes Disadvantages Time consuming (>30 min /sample) Difficult to detect small amount of undissolved solute Large amount of material is required

16. Analytical Methods for Solubility Measurements: HPLC ( High Performance Liquid Chromatography) UV (ultraviolet Spectroscopy) Fluorescence Spectroscopy Gas Chromatography

17. Advantages of Analytical methods: Direct analysis of aqueous samples High sensitivity Specific determination of drug conc. due to chromatographic separation of drug from impurities or degradation products