1. Faraza Javed Mphil Pharmacology

2. What is Gel? Pharmaceutical gels are semisolid systems in which there is interaction (either physical or covalent) between colloidal particles within a liquid vehicle. The vehicle is continuous and interacts with the colloidal particles within the three- 3. The vehicle may be: Aqueous Hydroalcoholic Alcohol based Or Non Aqueous 4. Brief History Franceso Selmi studied Inorganic Colloids in 1840. Modern Colloid Sciences- 1861. Thomas Graham introduced Colloids, Gels, Syneresis etc. Freundlick Research Weiser research on Gel- 1950 5. Gels Criteria The term Gel represents a physical state with properties intermediate b/w those of solids and liquids. It is often wrongly used to describe any fluid system that exhibit some degree of rigidity. 6. Gels Criteria Hermans in 1949 suggested some criteria for Gels: They are colloidal systems of at least two components (the Gelling agent and the fluid component). They exhibit the mechanical characteristics of the solid 7. Structure Of Gels 1. By Dispersion Of Solid Wander walls forces Electrostatic forces 2. By Dispersion Of Polymers Covalent Bonding 8. Types Of Gels Gels are classified in 2 ways. On the Basis of Continuous Phase. On the Basis of Nature of Bond involved in 3 Dimensional Solid Network. 9. Types Of Gels On the basis of continuous phase, gels are classified as: Organogels Hydrogels Xerogels 10. Organogels Solid material composed of liquid organic phase entrapped in three dimensional cross linked network. Non-crystalline Non-greasy Thermoplastic 11. Organogels Uses: In pharmaceutical industry. In cosmetics and food industry. 12. Hydrogels It is a network of polymer chains that are hydrophilic or colloidal gel in which water is the dispersion medium. Highly absorbent Degree of flexibility 13. Hydrogels Uses: As scaffolds in tissue engineering. As environment sensitivity detector. Sustained release DDS. Provide absorption and debriding. Contact lenses. ECG medical electrode. 14. Xerogels Gels in which vehicles has been removed, leaving a polymer network (e.g.) polymer film. Use: In DDS 15. Types Of Gels On the Basis of Nature of Bond involved in 3 Dimensional Solid Network. 1)Dispersed solids 2)Hydrophilic polymers i) Type I ii) Type II 16. Dispersed Solids Dispersed solids will undergo flocculation. The nature of interaction between particles in network may be vander waals or electrostatics interaction. Examples: Al-hydroxide gel USP 17. Hydrophilic Polymers Hydrophilic polymers are dispersed within appropriate aqueous phase. a)Type I: Irreversible system with 3 dimensional network formed by a covalent bonds between macromolecules. Example: Network is formed by 18. b) Type II: Reversible system in which interaction occurred between polymers by a hydrogen bonding. Temporary destruction of bonds when stress applied thus formulation enable to flow. 19. Pharmaceutical Consideration Of Pharmaceutical Gels Choice of vehicles Inclusion of buffers Preservatives Antioxidants Flavoring and coloring agents 20. Gelling Agent These are substances which, when added to an aqueous mixture, increase its viscosity without substantially modifying its other properties, such as taste. They provide body, increase stability, and improve suspension of added 21. Gelling Agent 3 types of Gelling Agents: 1. Natural Polymers Proteins Polysaccharides 2. Semi synthetic Polymers Cellulose Derivatives 3. Synthetic Polymers 22. Formulation There are 3 methods: Fusion Method Cold Method Dispersion Method 23. Fusion Method In this method various waxy materials employed as gellant in non polar media. Drug was added when waxy materials melted by fusion. stirred slowly until uniform gel formed. 24. Cold Method Water was cooled to 4-10c and placed it in mixing container. Gelling agent was slowly added and agitating until solution is complete. Maintained temperature below 10c . Drug was added in solution form slowly with gentle mixing. Immediately 25. Dispersion Method Gelling agent was dispersed in water with stirring at 1200 rpm for 30 min . Drug was dissolved in non-aqueous solvent with preservative. This solution was added in above gel with continuous stirring. 26. Preparation Of Gels 1. By freshly precipitating the dispersed phase upon reacting an inorganic agent, a gelatinous precipitate results. Example: Preparation of Al(OH)3 gel is by reacting AlCl3+NaHCo3. 27. Preparation Of Gels 2. By direct hydrating the inorganic material in water. Al2O3 + H2O Al(OH)3 28. Manufacturing Parameters Order of Mixing: The order of mixing of these ingredients with the gelling agent is based on their influence on the gelling process. If they are likely to influence the rate and extent of swelling of the gelling agent, they are mixed after 29. Manufacturing Parameters In the absence of such interference, the drug and other additives are mixed prior to the swelling process. In this case, the effects of mixing temperature, swelling duration, and other processing conditions on the physicochemical stability of 30. Manufacturing Parameters Ideally the drug and other additives are dissolved in the swelling solvent, and the swelling agent is added to this solution and allowed to swell . 31. Manufacturing Parameters Gelling Medium: Purified water is the most widely used dispersion medium in the preparation of gels. Under certain circumstances, gels may also contain co solvents or dispersing agents. A mixture of ethanol and toluene improves the dispersion 32. Manufacturing Parameters Alcohol improves the rheological stability of polyethylene oxide gels. Inclusion of glycerin, propylene glycol, sucrose, and alcohol improves the dispersion of sodium alginate dispersions. 33. Processing Condition The processing temperature, pH of the dispersion, and duration of swelling are critical parameters in the preparation of gels. These conditions vary with each gelling agent. 34. Processing Condition For instance, hot water is preferred for gelatin and polyvinyl alcohol, and cold water is preferred for methylcellulose dispersions. Carbomers, guar gum, hydroxypropyl cellulose, poloxamer, and tragacanth 35. Duration Of Swelling A swelling duration of about 24 48 hours generally helps in obtaining homogeneous gels. Natural gums need about 24 hours and cellulose polymers require about 48 hours for complete hydration. 36. Removal Of Entrapped Air Entrapment of air bubbles in the gel matrix is a common issue. Especially when the swelling process involves a mixing procedure or the drug and other additives are added after the swelling process. 37. Removal Of Entrapped Air Positioning the propeller at the bottom of the mixing container minimizes this issue to a larger extent. Further removal of air bubbles can be achieved by long - term standing, low-temperature storage, sonication, or inclusion of silicon antifoaming 38. Examples Of Topical Gels No . Active Ingredients Propriet ary Gelling Agent Route & Use 1. Clindamycin Cleocin T Gel Carbome r Acne Vulgaris 2. Cyanocobalami n Nascoba l Methyl Cellulos e Nasal: Hematol ogic 3. Metronidazole Metro- Gel Carbome r Vaginal: Bacteri a 4. Progesteron Suppliment Crinone- Gel Carbome r Progest eron 39. Properties Of Gels Swelling Syneresis Ageing Adsorption of vapours by Xerogel Rheological properties Chemical reactions in gels Diffusion in gels 40. Swelling Xerogel comes in contact with liquid(solvates it) Liquid taken up by the gel Volume of xerogel increases 41. A A A A A A A A A NETWORK SWELLING: DRUG CAN BE RELEASED = DRUG A =ANALYTE P = PROTEIN 42. Depends On: No. of linkages b/w molecules of gelling agent. Strength of linkages e.g. iso- electric point Presence of ions in swelling liquid e.g. Sulphate ions increases resistance to swelling by forming additional 43. Network consisting of primary valence bond e.g. in SILICIC ACID GEL the strength of bond is sufficient to prevent swelling. 44. Syneresis The contraction of the gel to exude some of the fluid medium Depends On: Conc. Of the gelling agent i.e. syneresis decreases as the conc. of gelling agent increases. Thermodynamic stability or 45. Ageing The slow spontaneous aggregation In gels ageing results in formation of denser network of gelling agent. Experiment: Theimer (1960) observed formation of additional thin 46. Adsorption Of Vapors By Xerogels Porous nature of xerogel leads to increased surface area as well as increased adsorption e.g. SILICA GEL used therefore as drying agent. The hysteresis loop b/w curves showing absorption and desorption shows 47. Reason Pores are filled with liquid in ABSORPTION. Pores are emptied in DESORPTION. 48. Chemical Reactions In Gels Leis gang rings Precipitates formed throughout the gel Gel acts as medium in which reaction can be studied Gel components inert towards substances involved in chemical reaction 49. Diffusion In Gels The soluble substances tend to permeate through gel by diffusion. Rate Of Diffusion Depends On: Diffusion in solution Presence of gel network 50. Diffusion In Solution SpontaneouS tranSference of solute from regions of higher conc. to lower conc. until uniform diStribution. Rate Of diffusion of solute explained by fickS first law: dm = -DAdc dt dx D of spherical particles is given 51. Presence Of Gel Network a. Sieve Effects: When the size of diffusing particles becomes larger than the pores the diffusion is retarded and ceases . It depends on conc. of gelling agent and the age of the gel. b.Other Effects: Adsorption of the diffusing solute onto the walls of the 52. Evaluation Of Gels pH determination Drug content Viscosity Spreadability Extrudability study In vitro release Stability 53. Drug content Amount of drug = conc. dilution factor conversion factor %age purity = Amount of drug 100 54. Spreadibility S = M. L/M M = wt. tied to upper slide L = Length of glass slide T = Time taken to separate the slides 55. Extrudability Studies Extrudability = Applied wt. to extrude gel from tube Area (in inches) 56. Application Of Gels Glycogelatin gels are used as a basis for medicated pestilles. Formulation of some suppositories e.g. Glycerin suppositories B.P. Used in Hard and soft gel capsules. Gelatin gels use as solid media 57. Application Of Gels Avoid oral drug degradation Extend the product for economical reasons e.g. paint Used in gel filtration Aerogels 58. References Tutorial Pharmacy Edited by S.J. Carter. Pharmaceutical Dosage Form by Howard C. Ansel. bentleyS Book Of Pharmaceutics, 8th Edition, Edited by E.A Rawlion. aultonS Pharmaceutics, 3rd Edition, Edited by E. Aulton. Pharmaceutics Dosage Form & Design by David Jones. www.pubmed.com