Physical Pharmacy Lecture 2 PDF

Faculty of Pharmacy & Drug Manufacturing PHYSICAL PHARMACY Surfactants or surface active agents S.A.A Are solutes or molecules that are adsorbed at the surface of a liquid or at the interface between two liquids, reducing the surface or interfacial tension. Composition...

Faculty of Pharmacy & Drug Manufacturing PHYSICAL PHARMACY Surfactants or surface active agents S.A.A Are solutes or molecules that are adsorbed at the surface of a liquid or at the interface between two liquids, reducing the surface or interfacial tension. Composition of soluble surfactants: all soluble surfactants consist of a lipophilic or hydrophobic group consisting of a long chain carbon which has little affinity for aqueous (polar) solvents + plus a hydrophilic or lipophobic group consisting of polar group such as –COOH or –OH …etc. which has affinity for polar solvents. These surfactants have both polar and non polar groups contributing to affinity for both aqueous and non aqueous (polar and non polar solvents), these are termed "amphiphils". 2  HLB- system Surfactants contain both polar and non polar groups in their molecules. Surfactants with more polar groups hydrophilic, mostly. Surfactants with more non-polar groups lipophilic, mostly. The balance between the hydrophilic and lipophilic nature of surfactants is given by HLB-system which consists of arbitrary scale of values to different surfactants based on their HLB = 20 𝑀ℎ 𝑀𝑡 Mh: molecular weight of hydrophilic group. Mt molecular weight of the whole molecules. In the HLB-system, each surfactant has a number typically between 1-20 representing the relative proportions of lipophilic and hydrophilic parts of molecule. The higher the number more hydrophilic. The lower the number more lipophilic. 3  𝟏𝟎𝟒𝟒 HLB = 20 x = 17 𝟏𝟐𝟐𝟔 Depending on HLB value for each surfactant different uses will be shown. HLB-values Surfactants 1 Oleic acid 3.8 Glyceryl monostearate (pure) 4.3 Sorbitan monooleate (Span 80) 4.7 Sorbitan monostearate (Span 60) 6.7 Sorbitan monopalmitate (Span 40) 8 Glyceryl monostearate (Self emulsifying) 8.6 Gum acacia 12 Sorbitan monolaurate (Span 20) 15 Triethanolamine oleate 16 Polyoxyethylene sorbitan monooleate (Tween 80) 17 Polyoxyethylene sorbitan monolaurate (Tween 20) 40 Sodium lauryl sulphate 5  Classification of surfactants (1)Anionic (2)Cationic (3)Nonionic (4)Amphoteric (1) Anionic Surfactants: which on dissociation long chain anion giving the surface activity with general formula of sulfate (OSO3-) while the cationic part inactive. These surfactants are not suitable for oral use because they have unpleasant taste and irritant action to the mucosa. Examples:- a- Alkali soaps: they are unstable below pH 10, are incompatible with acids e.g. potassium and sodium stearate. b. Amine soaps: as triethanolamine oleate produced from reactions of amines (triethanolamine) with fatty acids as oleic acid. c. Metallic soaps: salts of divalent or trivalent metals with long chain fatty acids as oleic acid. d. Alkyl sulfates and phosphates: are esters formed by reaction of fatty alcohols with sulfuric or phosphoric acid e.g. sodium lauryl sulfate. e. Alkyl sulfonate: including Dioctyl sodium sulfo succinate. (2) Cationic surfactants: They must be ionized or dissociated to be effective. In aqueous solutions dissociate to form +ve cations which give the surface activity ( emulsifying properties) with general formula of trimethyl ammonium N(CH3)3+. Example: quaternary ammonium compounds such as cetrimide (Cetyl trimethyl ammonium bromide ) and benzalkonium chloride (Benzyl trimethyl ammonium chloride). They are used as antiseptic, emulsifiers and preservative. (3)Ampholytic (Amphoteric) surfactants: They are substances whose ionic characters depend on the pH of the system. Below a certain pH( acidic) cation, and above the defined pH (alkaline) anionic, while at intermediated pH zwitterions. Example: lecithin, N-dodecyl-alanine.. (4) Non-ionic surfactants: are the largest group used in the pharmaceutical preparations. Advantages:- compatible with anionic and cationic S.A.A. resist the PH changes. resist the effect of electrolytes. less irritant. Disadvantages:- tend to inactivate preservation of phenolic or carboxylic groups. Example: 1-Brij & merj 2-Spans 3 Tweens 4 Macrogol esters or polyethylene glycol (PEG) 5 Glycerol monostearate How micelles are formed? 1. On addition of surfactants to water → the surfactant molecules (monomers) orient themselves at the liquid-air interface. 2. On adding more surfactants → the monomers adsorbed at the surface will be crowded till occupy the interface → the molecule of surfactant is compressed at the surface → crowded monomers. 3. On further addition of surfactant → the molecules of surfactant aggregate into micelles. Monomers Spherical micelle cylindrical micelle CRITICAL MICELLE CONCENTRATION 🞭 The concentration at which micelles are formed. 🞭 It is the concentration of the surfactant above which it will migrate to the bulk and start to form micelles and show the minimum value of surface tension.  WHY MICELLES ARE FORMED? 1. To achieve a state of minimum free energy (more stability). 2. To remove hydrophobic group form aqueous solution. Factors affecting CMC 1) Molecular structure of the surface active agent (A) The hydrocarbon chain the hydrophobic part: Chain length: the increase in chain length → ↑ micelle size so CMC. Branched hydrocarbon chain: branching → ↑ in CMC. Since the chain must come together in the micelle Unsaturation: the CMC is increased 3 - 4 times by the presence of double bond compared with saturated compounds. (B) The hydrophilic group: Type of hydrophilic group: if the ionic dissociation is complete → small effect on CMC. Number of hydrophilic groups: increase in number → ↑ in solubility of surfactant → ↑ in CMC. Position of hydrophilic group: when polar groups move from the terminal position to the middle → ↑ in CMC. 2) Effect of additives (A)Simple electrolytes: addition of salts → ↓ in CMC. (B) Alcohols: ↓ in CMC → aids the micelle formation. (C) Hydrocarbons: ↓ in CMC and micelle formation is facilitated. (D) Other surfactants: ↓ or ↑ in CMC. 3) Effect of temperature: Non-ionic surfactants → CMCs are decreasing monotonically with increasing temperature at first and increase afterward with increasing temperature. As the temperature increases, hydrogen bonding between the ethylene oxide chain and the surrounding water molecules is weakened and dehydration of the ethylene oxide groups occurs. Thus, the surfactant molecule becomes more hydrophobic shifting the onset of micelle formation toward lower concentrations. Now alkyl chain of the surfactant molecules starts to become more soluble with increasing temperature. Hence, the contribution of the hydrophobic alkyl chain is shifting the onset of micelle formation toward higher concentrations with increasing temperature. Temperature has a small effect on the micelle property of ionic surfactants. Applications of surface active agents (1) Medical applications: A- As antimicrobials: quaternary ammonium compounds such as benzalkonium chloride has useful antibacterial properties and used as disinfectant for instruments and as antimicrobial agents in eye drops and creams. B- As expectorants: by decreasing the viscosity of bronchial mucous on inhalation of sprays containing surfactants in cases of acute and chronic infections of upper respiratory tract. C- As cleansing agents: surfactants have detergent properties. (2) Pharmaceutical applications: A- As solubilizing agents are used extensively as solubilizing agents for a number of poorly soluble drugs such as oil soluble vitamins, volatile oils, hormones…etc. also as solubilizers for many disinfectants compounds as cresol or chloroxylenol and the disinfectant property is increased by the use of surface-active agents by altering (changing) the permeability of the cell membrane of microorganism. B- As wetting agents: surfactants adsorbed at the solid /liquid interface between the powder particles and the solvent leading to increase in affinity of hydrophobic powder of water. C- As flocculating agents: surfactants make controlled flocculation for powder particles in suspensions preventing cake formation. D- As emulsifying agents: acting by reducing the interfacial tension between the oil phase and water phase by forming the stable interfacial film between them e.g. tween and span. E- As additives in semisolid preparations: are added to ointments and creams to change the release characteristic of the incorporated drug resulting increase in absorption through the skin.