Colloidal dosage Forms Dr. rer. nat. Rebaz H. Ali

Transcription

1 University of Sulaimani School of Pharmacy Dept. of Pharmaceutics Third level - Second semester Colloidal dosage Forms Dr. rer. nat. Rebaz H. Ali

2 Outlines Disperse systems Introduction Lyophilic Lyophobic Gels Aerosols Association colloid Micelles Pharmaceutical application of colloidal system 4/3/2017 Pharmaceutical Compounding 2

3 Introduction Dispersion system consist of at least two phases: one or more dispersed or internal phases, and a continuous or external phase called the dispersion medium or vehicle. Colloidal dispersions can be characterized as containing particles in the size range of between approximately 1 nm and 1 micrometer, e.g. blood, milk, micelles and etc. sol is a general term which means dispersion of a colloidal solid substance in a liquid, or gaseous medium Hydrosol, alcosol, and aerosol 4/3/2017 Pharmaceutical Compounding 3

4 Introduction cont. Category Particle Size Characteristics Examples Molecular solution of small molecules and ions < 10 A o lower limit of resolution by electron microscope high rates of diffusion pass through filter paper, ultra filter and dialysis membranes high osmotic pressure NaCl, sucrose in water Colloidal dispersions 10 A o - 1μm Visible in electron microscope and invisible in ordinary microscope low rate of diffusion undergo Brownian motion pass through filter paper, retained by ultrafilter and dialysis membranes low osmotic pressure. Bacterial and virus suspension, sod. CMC in water, surfactant micelles Coarse dispersion > 1μ Visible in ordinary microscope retained by filter paper no diffusion no Brownian motion settle out or cream negligible osmotic pressure Most pharmaceutical suspension and emulsions. 4/3/2017 Pharmaceutical Compounding 4

5 Diffusion and sedimentation The continuous motion of the colloidal particles causing collisions and the random bombardment imparts and erratic movement called brownian motion. Brownian motion prevents sedimentation A common measure of the mobility of a dissolved molecule or suspended particle in a liquid medium is the diffusion coefficient. D = RT 6πηrN As particle size or r increases, brownian motion decreases. With increased vehicle viscosity, the diffusion coefficients are decreased. 4/3/2017 Pharmaceutical Compounding 5

6 Outlines Disperse systems Introduction Lyophilic Lyophobic Gels Aerosols Association colloid Micelles Pharmaceutical application of colloidal system 4/3/2017 Pharmaceutical Compounding 6

7 Lyophilic dispersions A. lyophilic Dispersions The system is said to be lyophilic (solvent-loving) if there is considerable attraction between the dispersed phase and the liquid vehicle. Due to the presence of high concentrations of hydrophilic groups, solids swell, disperse, or dissolve spontaneously in water. Hydrophilic colloidal dispersions can be further subdivided as: True solutions: water-soluble polymers (e.g., acacia). Gelled solutions: Particulate dispersions: solids remain as discrete though minute particles (e.g., bentonite). 4/3/2017 Pharmaceutical Compounding 7

8 The electrical double layer The surface charge influences the distribution of ions in the aqueous medium Ions of opposite charge to that of the surface, termed counter-ions, are attracted towards the surface i Ions of like charge, termed co-ions, are repelled away from the surface. Zeta potential is a property of an electric structure that is usually built up at interfaces i.e. double layer. Higher the zeta-potential, the more stable the colloid. When the zeta-potential equals zero, the colloid will precipitate into a solid. 4/3/2017 Pharmaceutical Compounding 8

9 The electrical double layer cont. Due to Brownian motion, the colloidal particle collision whether result in permanent contact of the particles (coagulation) the particles rebound and remain freely dispersed. These forces can be divided into three groups: Electrical forces of repulsion Forces of attraction Forces arising from solvation. Aggregation is a general term signifying the collection of particles into groups. Coagulation signifies that the particles are closely aggregated and difficult to redisperse. 4/3/2017 Pharmaceutical Compounding 9

10 Outlines Disperse systems Introduction Lyophilic Lyophobic Gels Aerosols Association colloid Micelles Pharmaceutical application of colloidal system 4/3/2017 Pharmaceutical Compounding 10

11 B. Lyophobic dispersion Lyophobic (solvent-hating) dispersions are unstable and irreversible because of the lack of attraction between the dispersed and continuous phases. The van der Waals attractive forces between the particles are stronger than the solvation forces, therefore, the particles tend to aggregate. The dispersed phase is coalesced into large drops. Examples of materials that form hydrophobic dispersions cholesterol, sulfur, paraffin wax and etc. 4/3/2017 Pharmaceutical Compounding 11

12 Outlines Disperse systems Introduction Lyophilic Lyophobic Gels Aerosols Association colloid Micelles Pharmaceutical application of colloidal system 4/3/2017 Pharmaceutical Compounding 12

13 Gels Gels (jellies) are semisolid systems consisting of dispersions colloidal particles in an aqueous liquid vehicle. The particles link together to form a network, thus imparting rigidity to the structure. The flexible chains of dissolved polymers interpenetrate and entangle because of the constant brownian motion of their segments. Each chain is encased in a sheath of solvent molecules that solvate its functional groups. Gels are more rigid than jellies because gels contain more covalent crosslinks, a higher density of physical bonds, or simply less liquid. Gels either single-phase or two-phase (magma) 4/3/2017 Pharmaceutical Compounding 13

14 Gels Imbibition is the taking up of a certain amount of liquid without a measurable increase in volume. Swelling is the taking up of a liquid by a gel with an increase in volume. Syneresis occurs when the interaction between particles of the dispersed phase becomes so great that on standing, the dispersing medium is squeezed out in droplets and the gel shrinks. Xerogel is the removing of the liquid remaining only the gel framework 4/3/2017 Pharmaceutical Compounding 14

15 Classification According to the dispersion Gelation of lyophobic sols Gelation of lyophilic sols Chemical Physical 4/3/2017 Pharmaceutical Compounding 15

16 Gelation of lyophobic sols Clays such as bentonite, aluminium magnesium silicate (Veegum) and kaolin form gels by flocculation. The forces holding the particles together in this type of gel are relatively weak van der Waals forces. They show phenomena of thixotropy. If a thixotropic gel is sheared these weak bonds are broken and a lyophobic sol is formed. This phenomenon of thixotropy is employed in the formulation of pharmaceutical suspensions, e.g. bentonite in calamine lotion. 4/3/2017 Pharmaceutical Compounding 16

17 Gelation of lyophilic sols Type I Type II Chemical gel Physical gel The interaction between the polymer chains is covalent and is mediated by molecules that cross-link the adjacent chains Hydrogen bonds and van der Waals interactions maintain the gel network Reversible Irreversible Cross links Polymer chains Junction zones Polymer chains 4/3/2017 Pharmaceutical Compounding 17

18 Examples Natural polymers include polysaccharides (acacia, agar, pectin, sodium alginate, tragacanth, xanthan gum) and polypeptides (gelatin). Cellulose derivatives are produced by chemically modifying cellulose. MC, NaCMC, HEC, HPC, and HPMC. Water-soluble synthetic polymer: PEG, PEO, PVP, and carbomer. Cellulose 4/3/2017 Pharmaceutical Compounding 18

19 Outlines Disperse systems Introduction Lyophilic Lyophobic Gels Aerosols Association colloid Micelles Pharmaceutical application of colloidal system 4/3/2017 Pharmaceutical Compounding 19

20 Aerosol Pharmaceutical aerosols are pressurized dosage forms that, upon actuation, emit a fine dispersion of liquid and/or solid materials containing one or more active ingredients in a gaseous medium. They differ from most other dosage forms in their dependence upon the function of the container (valve assembly), and an added component (the propellant). They ay be designed to expel their contents as a fine mist; a coarse, wet, or dry solid particles; foam. 4/3/2017 Pharmaceutical Compounding 20

21 Aerosol cont. Medicated or cosmetic aerosol could be used by Inhalation In inhalation aerosol, degree of respiratory penetration depends on the particle size. Topically (skin, vaginal or rectal) 4/3/2017 Pharmaceutical Compounding 21

22 Aerosol cont. Aerosols used to provide an airborne mist are termed space sprays. Room disinfectants and room deodorizers The particle size of the released product is generally quite small Aerosols intended to carry the active ingredient to a surface are termed surface sprays or surface coatings. Deodorant, perfumes, paint spray and etc. 4/3/2017 Pharmaceutical Compounding 22

23 Aerosol formulation An aerosol formulation consists of two component parts: the product concentrate and the propellant. Product concentrate is the active ingredient of the aerosol combined with the required adjuncts The propellant is a liquefied gas like chlorofluorocarbons Dichlorodifluoromethane or dichlorotetrafluoroethane Or compressed gases Carbon dioxide, nitrogen, and nitrous oxide. 4/3/2017 Pharmaceutical Compounding 23

24 Valve assembly The function of the valve assembly is to permit expulsion of the contents of the can in the desired form, at the desired rate, and in the case of metered valves, in the proper amount or dose. 4/3/2017 Pharmaceutical Compounding 24

25 Outlines Disperse systems Introduction Lyophilic Lyophobic Gels Aerosols Association colloid Micelles Pharmaceutical application of colloidal system 4/3/2017 Pharmaceutical Compounding 25

26 C. Association Colloids Organic compounds that contain large hydrophobic moieties on the same molecule with strongly hydrophilic groups are said to be amphiphilic. The individual molecules are generally too small to be in the colloidal size range, but they tend to associate into larger aggregates when dissolved in water or oil. Surfactant (called surface active agents and associated colloid), are compounds which, is soluble in a given a liquid and adsorbed at its interfaces. If the surfactant molecule contains ions, it is classified as ionic otherwise the surfactant is said to be non-ionic Hydrophilic hydrophobic 4/3/2017 Pharmaceutical Compounding 26

27 C. Association Colloids cont. Anionic surfactant Soaps are the oldest surfactants, it is the sodium or potassium salt of lauric or oleic acid. The bile salts sodium glycocholate and sodium taurocholate emulsify triglyceride in the intestine and solubilize monoglycerides. Cationic surfactants: These are quaternary ammonium compounds, They have bacteriostatic activity Examples are ceylpyridinium chloride, benzalkonium chloride. 4/3/2017 Pharmaceutical Compounding 27

28 C. Association Colloids cont. Amphoteric agents They are containing carboxylate or phosphate groups such as the anion, and amino or quaternary ammonium groups such as the cation, e.g. phosphatidylcholine (lecithin). Non ionic surfactant These surfactants do not have any charge. E.g. sorbitan ester (Span), polysorbate (Tween) and poloxamer. Sorbitan monoester Polyethoxylated monosester 4/3/2017 Pharmaceutical Compounding 28

29 Outlines Rheology Surface and interfacial tension Colloidal dispersions Gel formation Micelles Pharmaceutical application of colloidal system 4/3/2017 Pharmaceutical Compounding 29

30 Micelles As the surfactant concentration in a liquid is increased, the amount of the surfactant adsorbed at the liquid-air and liquid interfaces increases and these interfaces become crowded. At a given concentration and temperature all micelles of a given surfactant usually contain the same number of molecules (25 to 100). The diameters of micelles are approximately between 30 to 80 A o. The lowest concentration at which micelles first appear is called the critical micelle concentration. 4/3/2017 Pharmaceutical Compounding 30

31 Micelles cont. The number or concentration of micelles increases proportionally with the total surfactant concentration. Micelles formed in dilute aqueous solutions are approximately spherical. In more concentrated aqueous solutions of surfactants, micelles change from spherical either to cylindrical or lamellar shapes. 4/3/2017 Pharmaceutical Compounding 31

32 Critical micelle concentration Osmotic pressure Solubility Surface tension Interfacial tension Equivalent conductivity 4/3/2017 Pharmaceutical Compounding 32

33 Outlines Rheology Surface and interfacial tension Colloidal dispersions Gel formation Micelles Pharmaceutical application of colloidal system 4/3/2017 Pharmaceutical Compounding 33

34 Pharmaceutical application of colloidal systems Microemulsion Microemulsions are liquid dispersions of water and oil that are made homogeneous, transparent, and stable by the addition of relatively large amounts of a surfactant and a co-surfactant. Microemulsion droplets have a mean diameter range of approximately 6 to 100 nm. Microemulsions require a co-surfactant (linear alcohol). The advantage of microemulsions Smaller droplet size, which increases drug release, superior physical stability. Emulsion Microemulsions 4/3/2017 Pharmaceutical Compounding 34

35 Pharmaceutical application of colloidal systems Liposomes Liposomes are synthetic spherical vesicles consisting of an aqueous core surrounded by one or more concentrically arranged bilayer membranes. These membranes are commonly composed of phospholipids or lipid and surfactant. Small unilamellar Large unilamellar Multilamellar vesicles Due to their bilayer structure liposomes are able to accommodate water- and lipid-soluble molecules. 4/3/2017 Pharmaceutical Compounding 35

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