Published on March 24, 2009
Slide 1: SEMISOLIDS Amit M. Gupta Lecturer Agnihotri Collage of pharmacy, Wardha Slide 2: Management of illness through medication has entered an era of rapid growth. The goal of any drug delivery system is to provide therapeutic level of drug at the target site in the body and also to achieve and maintain the desired concentration. Today, there are a most of drug for combating virtually every disease or condition known to man and a variety of means by which these drugs are delivered to human body for therapy such as tablet, capsules, injection, aerosols, creams, ointments, suppositories, liquids etc., often referred to as conventional drug formulation Slide 3: Semisolids -Ointments -Pastes -Cream emulsion, -Gels -And ridgid forms Slide 4: Ointments Ointments, are composed of fluid hydrocarbons While most ointment are based on mineral oil and petrolatum Polyethylene can be incorporate into mineral oil to yield a plastic matrix. Mixture of polyethylene glycol can yield product of ointment consistency i.e. water- soluble. Slide 5: -Common property is the availability to cling to the surface of application for reasonable duration before washed off. -This adhesion is due to their plastic rheologic behavior, which allows semisolids to remain their shape and cling ad a film until acted upon by an outside force, in which case they deform and flow. Slide 6: Skin and drug permeation For understanding the concept, it is important to review the structural and biochemical features of human skin and those characteristics which contribute to the barrier function and the rate of drug access into the body via skin. Slide 7: The skin The skin is one of the most extensive organs of the human body covering an area of about 2m2 in an average human adult. The multilayered organ receives approximately one third of all blood circulating through the body. The skin is composed of three layers: the epidermis, the dermis, and the hypodermis. Slide 9: The epidermis results from an active epithelial basal cell population and is approximately 150 micromeres thick. It is the outer most layer of the skin and process of differentiation results in migration of cell from basal layer towards the skin surface. The end result of this process is the formation of thin, stratified and extremely resilient layer (the stratum corneum) at the skin surface. Below this layer is the outer most layer of epidermis - the stratum lucidum, stratum granulosum, stratum spinosum, stratum gerinativum. Slide 10: Together this other layers constitute the viable epidermis. The stratum corneum or horny layer is the rate limiting barrier that restricts the inward and outward movement of chemical substances. The innermost layer is the 2 to 3 mm thick dermis, which is a matrix of various cells including those that produced collagen and other fiber proteins. Hair follicles, subcutaneous glands and sweat glands are also part of dermis. Slide 11: Percutaneous Absorption Percutaneous absorption involves the transfer of drug from skin surface in to stratum corneum, under the aegis of a concentration gradient and its subsequent diffusion through the dermis and in to microcirculation the skin behaves as a passive barrier to diffusing molecules. Slide 12: The process of percutaneous absorption can be described as follows, when a drug system is applied topically the drug diffuse, passively out of its carrier or vehicle and depending on where the molecules are placed down, it partitions in to either the stratum corneum or the sebum-filled ducts of the pilosebaceous epidermal and dermal points of entry in this way, a concentration gradient’s established across the skin up to the outer reaches of the skin’s microcirculation, where the drug is swept away by the capillary flow and rapidly distributed throughout the body. The greatest resistance to penetration is met in the stratum corneum i.e. diffusion through the stratum corneum tends to be the rate limiting step in percutaneous absorption. Slide 13: Kinetics of permeation Skin permeation kinetics is vital for successful permeation of drug, involve following steps. · Sorption by stratum corneum · Penetration of drug through viable epidermis · Uptake of drug by capillary network in dermal papillary layer This permeation can be possible only if drug possesses certain physicochemical properties .The rate of permeation across the skin (dQ/dt) is given by dQ ----- = Ps (Cd -Cr) -----------------------eqn (1) dt Where Cd and Cr are, the concentrations of skin penetrate in donor compartment and receptor compartment respectively. Ps is the overall permeability coefficient of the skin tissue to penetrant. Slide 14: Skin structure 2.Epidermal diffusion ?Clearance from dermis Clearance from dermis depends on Effective blood flow Intestinal fluid movement Lymphatic Other factor with dermal constituents 3.Drug solubility characteristics Factor affecting Percutaneous absorption Slide 15: 4. Concentration of medication (Conc. of drug) (DA) dq/dt = p.c ------------------------------- L p.c is the effective partition coefficient of the penetrant between the vehicles and the barrier of the skin D is the effective average diffusivity of the penetrant in the barrier phase A effective cross section area L thickness of barrier Slide 16: 5. Vehicles 6. Skin condition 7. Penetration enhancers 8. Miscellaneous factor Slide 17: Route of Penetration Follicular region Through the sweat ducts Through the unbroken stratum corneum between these appendages Slide 18: Study methods In vitro technique Using artificial or animal skin on diffusion cell In vivo technique Use of tracers Analysis of body tissue and fluids Elicitation of biological response Slide 19: Factors in skin penetration 1.physicochemical properties of drug Ø Solubility of drug Ø Water/lipid partition coefficient Ø Molecular size and weight 2. physicochemical properties of vehicles, pH and concentration Slide 20: Penetration enhancer Penetration enhancer or promoter are agents that have therapeutic properties of these own but can transport the sorption of drug from drug delivery system, on to the skin or their subsequent site through skin. The acceleration across the keratin to swell and leaches out essential structural materials from the stratum corneum, thus reducing diffusional resistance and increasing the permeability of drug through skin. Ideal properties of penetration enhancers : Ideal properties of penetration enhancers It should be non toxic, non irritant, non allergenic. The action should be immediate and the effect should be suitable and predictable. Upon removal of the material, skin should be immediately and completely recover it’s normal barrier properties. Slide 22: The enhancer should not cause loss of body fluids, electrolytes or other endogenous materials. It should be comparable with all drug and excipients. The substance should be good solvent for drug. The material should having good spreadability and skin “feel”. It should be odour less, tasteless, colourless, and inexpensive. Chemical should formulate in all the verity of preparation used topically. Slide 23: No single material should posses all these desirable properties in development of penetration enhancers, to improve low permeability of drug across the skin. An effective amount of penetration enhancer increases the skin permeability and correspondingly the desired depth of permeation rate and amount of drug delivered. Slide 24: Mechanism of penetration enhancer These are compounds which promotes skin permeability by altering the skin as a barrier to the flux of a desired penetrant. The flux, J of drug across the skin can be written as: dc J = D ------ dx Where D is the diffusion coefficient and is a function of size, shape and flexibility of the diffusing molecules as well as the membrane resistance; C is the concentration of the diffusing species; x is the co-ordinate. Slide 25: Vehicles and skin penetration Vehicles alter the activity of water in the stratum corneum and influence the stratum corneum /vehicles partition coefficient ex. Greases and oil, emulation of w/o Humectants which have a high affinity for water may under certain circumstances dehydrates the stratum corneum and decreases penetration Powders increases the surface area and increases the rate of evaporation of water and so decreases the extends of hydration. Slide 26: Materials have been externally studied in attempted to increase the weight of absorption of topically applied drug. These agents are also called as accelerants. Examples: Dimethylsulfoxide DMSO Dimethylformamide DMF Diethylacetamide DMA Urea Propylene glycol Surface- active agents Slide 27: All strongly hygroscopic and it is likely that the presence of these substance in stratum corneum increases the hydration and permeability. When penetration occurs anion penetrates best fallowed by cationic and nonionic surfactants Penetration of fatty acid soap varies inversely with pH. At high pH (approximately 11), the action of the anionic surfactant appears to be attenuated or overshadowed by the influence of the more alkaline pH itself. Slide 28: Ointment Bases Hydrocarbons Petrolatum and Mineral oil 2.Hydrocarbons contains aliphatic cyclic, saturated, unsaturated, Branched and unbranched substances. 3.Hydrocarbons Waxes To increase viscosity of Mineral oil and also to prevent its separation from an ointment. Eg. Ozokerite Paraffin wax Ceresin ( Mixture of Ozokerite and Paraffin wax) Synthetic waxes : They exhibits thermoplasticity Eg. Synchrowaxes Slide 29: Oleaginous substances Vegetable oils Peanut oil Almond oil Sesame oil Olive oil Slide 30: Fatty acids and Alcohols Stearic acid-used in water–removable cream as an emulsifiers to developed a certain consistency in the cream to give matt effect on the skin. Stearyl alcohol and cetyl alcohol are used in cream as auxiliary emulsifiers and emollients. Palmic acids Slide 31: Emulsifiers To stabilized the emulsion eg. Fatty polar substance like cetyl alcohol and glyceryl monosterate Cationic eg. Cetyl trimethyl ammonium chloride Nonionic eg. Promulgens, SLS Emulsifiers are selected according to HLB systeme The calculation of HLB value to optimize the emulsion. Polyols Glycerine Propylene glycol Sorbitol 70% As humectants in creams, thy also improve the consistency and rub-out qualities of the cream Sorbitol 70%is more hygroscopic than glycerine and used in low conc.n (3% ) Slide 32: Vehicles # Hydrocarbon bases Petrolatum and white ointment, i.e. petrolatum with 5% bees wax are typical of this class of lipophilic vehicles. # Absorption Bases Lanolin, lanolin, isolates, cholesterol, lanosterol, acetylated sterols, polyhydric alcohols # Emulsion form # Water- removable bases # O/w vehicles # Water soluble bases # PEG bases # Low molecular weight bases Slide 33: Paste Gels and jellies Ophthalmic ointments Slide 34: Preservation of ointments Rheologic consideration Equipments Low energy Emulsifiers Homogenizers Storage of semisolids Slide 35: Thank You
some of which deliver foams or semisolid ﬂuids. In the case of Inhalation Aerosols, ... 1260 IN-PROCESS REVISION Vol. 35(5) [Sept.–Oct. 2009]
Modelling of rheological behaviour of semisolid metal slurries Part 4 – Effects of particle morphology Z. Fan and J. Y. Chen In this part ofthe series ...