Pharmaceutical semisolid dosage forms creams and gels: Pharmaceutical semisolid dosage forms creams and gels Raghunadha sarma s.v.s M.Pharmacy pharmaceutical Technology Srinivasa Rao College of Pharmacy Visakhapatnam: Raghunadha sarma s.v.s M.Pharmacy pharmaceutical Technology Srinivasa Rao College of Pharmacy Visakhapatnam PowerPoint Presentation: Pharmaceutical semisolid preparations may be defined as topical products intended for application on the skin or accessible mucous membranes to provide localized and sometimes systemic effects at the site of application. PowerPoint Presentation: In general, semisolid dosage forms are complex formulations having complex structural elements. They are often composed of two phases (oil and water), one of which is a continuous (external) phase and the other a dispersed (internal) phase. W/O O/W oil water o il water PowerPoint Presentation: Semisolid dosage forms include, Ointments Pastes Creams Gels All these preparations cling to surface of application for reasonable duration. This adhesion is due to plastic rheologic behaviour. PowerPoint Presentation: All these semisolid preparations cling to surface of application for reasonable duration. This adhesion is due to plastic rheologic behaviour. And mostly the surface of application is skin. CREAMS: CREAMS BP DEFINITION: “Creams are formulated to provide preparation that are essentially miscible with skin secretion. they are intended to be applied to the skin or certain mucous membranes for protective, therapeutic, or prophylactic purposes especially when occlusive effect is not necessary.” BRIEF HISTORY: BRIEF HISTORY Claudius Galen (131–201) prepared the first unguentum refrigerans or ‘‘cold cream,’’ an ointment containing olive oil, rose oil, white wax, and a small quantity of water. This was a prototype for other cosmetic ointments introduced by Johann Mesue, Jr., in the thirteenth century. BRIEF HISTORY: BRIEF HISTORY A modern version, consisting of almond oil, spermaceti, white wax, and rose water, passed into the United States Pharmacopeia as ‘‘Rose Water Ointment’’ or ‘‘Galen’s Cerate.’’ Pharmaceutical creams became official with the introduction of the formula for a ‘‘Sun Cream’’ in the National Formulary VIII (1946), a product designed to prevent sunburn but permit tanning. TYPES OF CREAMS: TYPES OF CREAMS Hydrophilic creams (Oil-in-Water creams) contain large amounts of water in their external phase. Example: Vanishing cream. Hydrophobic creams (Water-in-Oil creams) contain water in the internal phase. Example: Cold cream. TYPES OF CREAMS: TYPES OF CREAMS Types of creams depending on formulation are as follow, 1) Sterol Creams: They are water in oil emulsions where emulgent is wool fat or wool alcohol. Classical example is lanolin. TYPES OF CREAMS: TYPES OF CREAMS Types of creams (contd.), 2) Soap Creams: Triethanolamine Creams are neutral soaps, produces o/w emulsion with oleic acid and triethanolamine (good emulsifying agents gents for liquid paraffin). TYPES OF CREAMS: TYPES OF CREAMS Types of creams depending on formulation are as follow, (contd.) 3) Anionic Emulsifying Wax Creams: These emulsifiers produce oil in water type. 4) Cationic Emulsifying Wax Creams: These emulsifiers produce water in oil type. 5) Creams Emulsified with Non-ionic Surfactants: Cream bases prepared with Self emulsifying monostearin, a sorbitan ester, a macrogol ester, a non emulsifying wax containing a macrogol ether etc. TYPES OF CREAMS: TYPES OF CREAMS Types of creams depending on formulation are as follow, (contd.) 6) Divalent Creams: Classical example is Lime creams which is of water in oil type. Emulgent in these is Oleic acid and Calcium hydroxide. 7) Vanishing Creams: They are oil in water type creams which when rubbed onto the skin and disappear with little or no trace of their former presence. GELS: GELS DEFINITION: Gels are semisolid organic or inorganic colloids rich in liquid, consisting of hydrated threads or granules of the dispersed phase intimately associated with the dispersion medium. BRIEF HISTORY: BRIEF HISTORY Although Francesco Selmi studied inorganic colloids in the 1840s, modern colloid science began in 1861 with the work of Thomas Graham, who investigated diffusion and dialysis and introduced such terms as colloid, glue, sol, gel, peptization, and syneresis. In the early 1900s, Freundlick introduced the terms lyophilic and lyophobic to describe colloids in which the dispersed phase has a high or a low affinity, respectively, for the dispersion medium. BRIEF HISTORY: BRIEF HISTORY In 1950, Weiser divided gels into inorganic gels, which include gelatinous precipitates (such as Milk of Magnesia) and inorganic jellies (such as Bentonite Magma), organic gels or jellies (such as Pectin Paste), and crystalline or amorphous jellylike networks in which both solid and liquid phases are continuous TYPES OF GELS: TYPES OF GELS Gels may be classified into two primary types: Hydrogels, which have an aqueous continuous phase, and Organogels, which have an organic solvent as the liquid continuous medium. TYPES OF GELS: TYPES OF GELS Gels may also be classified based on the nature of the bonds involved in the three-dimensional solid network: Chemical gels and, Physical gels. TYPES OF GELS: TYPES OF GELS Chemical gels form when strong covalent bonds hold the network together, and, physical gels form when hydrogen bonds and electrostatic and van der Waals interactions maintain the gel network. TYPES OF GELS: TYPES OF GELS Gels may also be classified as, Two-phase systems and, Single-phase systems. TYPES OF GELS: TYPES OF GELS TWO PHASE SYSTEM: A two-phase gel system consists of floccules of small distinct particles rather than large molecules, thus called a two-phase system often referred to as a magma. The gel structure in the two-phase systems is not always stable and thus may thicken on standing, forming a thixotrope, and must be shaken before use to liquefy the gel and enable pouring. TYPES OF GELS: TYPES OF GELS TWO PHASE SYSTEM (Contd.): Milk of magnesia (or magnesia magma), which comprises a gelatinous precipitate of magnesium hydroxide, is an example of such a system. TYPES OF GELS: TYPES OF GELS SINGLE PHASE SYSTEM : Single-phase systems are gels in which the macromolecules are uniformly distributed throughout a liquid with no apparent boundaries between the dispersed macromolecules and the liquid. Examples of Single phase system gels include, Tragacanth and, Carboxymethylcellulose. FORMULATION COMPONENTS OF SEMI SOLID DOSAGE FORMS: FORMULATION COMPONENTS OF SEMI SOLID DOSAGE FORMS ANTIOXIDANT Prevents or slows oxidation of other components. Examples: Tocopherol , butylated hydroxy toluene, or a reducing agent such as ascorbic acid FORMULATION COMPONENTS: FORMULATION COMPONENTS BASE: Bases act as vehicles to deliver the drug and to impart emollient and lubricant properties to the preparation. Examples: Petrolatum, white petrolatum, yellow or white ointment, or mineral oil, Lanolin, cholesterol. FORMULATION COMPONENTS: FORMULATION COMPONENTS BUFFER: Acid-conjugate base mixture employed to control pH and therefore control ionization state of drug and impart stability. Examples: Citrate buffer, Phosphate buffer, Tartarate buffer. FORMULATION COMPONENTS: FORMULATION COMPONENTS CHELATING AGENT: Have the ability to bind metal ions; prevents auto-oxidation phenomena frequently catalyzed by metal ions and enhances action of preservatives by binding iron and copper ions essential to microbial growth. FORMULATION COMPONENTS: FORMULATION COMPONENTS CHELATING AGENT: Some common examples of chelating agents include, EDTA, Citric acid. FORMULATION COMPONENTS: FORMULATION COMPONENTS EMULSIFYING AGENT: Emulsifying agent helps in reducing the surface tension of two phases in an emulsion, preventing coalescence of individual phases. Examples: Detergent, Emulsifying wax (detergent-treated wax), Cetostearyl alcohol, Polysorbate 20. FORMULATION COMPONENTS: FORMULATION COMPONENTS HUMECTANT: Promotes retention of water in a mixture. Examples: Glycerin, propylene glycol, polyethylene glycols (low MW). FORMULATION COMPONENTS: FORMULATION COMPONENTS PERMEATION ENHANCER: Permeation enhancer facilitates diffusion process of active ingredient across the stratum corneum by chemical modification. FORMULATION COMPONENTS: FORMULATION COMPONENTS PERMEATION ENHANCER: Examples: Ethanol, Oleic acid, Propylene glycol, Polyethylene glycol (400). FORMULATION COMPONENTS: FORMULATION COMPONENTS PRESERVATIVE: Prevents or slows microbial growth; may be one of 4 major compound types: acid, alcohol, quaternary ammonium compounds, or organic Mercurial. FORMULATION COMPONENTS: FORMULATION COMPONENTS PRESERVATIVE: Examples: Acid: benzoic acid; Alcohol: phenyl ethyl alcohol; Quaternary ammonium: stearyl dimethyl benzyl ammonium chloride; Organic mercurial: thimerosal. FORMULATION COMPONENTS: FORMULATION COMPONENTS THICKENING AGENT: Thickening agent increases viscosity of the semisolid preparation. They may be derived from natural, semi-synthetic, or synthetic sources. FORMULATION COMPONENTS: FORMULATION COMPONENTS THICKENING AGENT: Examples: Natural: cellulose, pectin; Semi-synthetic: methylcellulose, (sodium) carboxymethylcellulose; Synthetic: Carbopol. FORMULATION COMPONENTS: FORMULATION COMPONENTS FRAGRANCES: Give agreeable odour to the formulation. Examples: Examples of widely use fragrances are Lavender oil, Rose oil, Lemon oil, Almond oil further look on some components BASES: further look on some components BASES A base should be compatible with skin, stable, smooth and pliable, non-irritating, non-sensitizing, inert, capable of absorbing water or other liquid preparations, and of releasing the incorporated medicament, readily. It should also be sterilizable conveniently. BASES: BASES Appropriate Selection of Base: Selection of ointment base depends on following. 1. Desired release rate of the drug substance from the ointment base. 2. Rate and extent of topical or percutaneous drug absorption. BASES: BASES Appropriate Selection of Base(contd.): Selection of ointment base depends on following. 3. Desirability of occlusion of moisture from skin. 4. Stability of the drug in the ointment base. BASES: BASES Appropriate Selection of Base(contd.): Selection of ointment base depends on following. 5. Effect of drug on the consistency of base. 6. Easy removal of base on washing. 7. Characteristic of the surface to which it is applied. BASES: BASES Bases may be classified in several ways but the following classification based on composition is generally used which are as follow, A) Hydrocarbon bases. B) Absorption bases. C) Emulsion bases. D) Water soluble bases. E) Water removable bases. BASES: BASES HYDROCARBON BASES: Also known as oleaginous bases, the hydrocarbon bases are essentially water-free, incorporating aqueous preparations only in small amounts and with considerable difficulty. BASES: BASES HYDROCARBON BASES: The primary features of this type of base include its emollient effect, retention on the skin for prolonged periods, prevention of escape of moisture from the skin to the atmosphere, and difficulty in washing off. BASES: BASES Common examples of these bases include: Petrolatum, USP, White petrolatum, USP, Yellow ointment, USP, Mineral oil. BASES: BASES ABSORPTION BASES: These are essentially anhydrous systems composed of hydrophobic ingredients already discussed under oleaginous bases. They are called as emulsifiable bases because they initially contain no water but are capable of taking it up to yield W/O and O/W emulsions. BASES: BASES ABSORPTION BASES: Absorption bases are W/O type emulsions and have capacity to absorb considerable quantities of water or aqueous solution without marked changes in consistency. BASES: BASES ABSORPTION BASES: Absorption bases are mostly mixtures of animal sterols with petrolatum. Combinations of cholesterol and/or other suitable lanolin fractions with white petrolatum are available under different commercial names e.g. Eucerin and Aquaphor. BASES: BASES ABSORPTION BASES: A typical example of an anhydrous absorption base is hydrophilic petrolatum, USP. Hydrophilic petrolatum, USP (anhydrous absorption base) White petrolatum 86.0 (% w/w) Cholesterol 3.0 (% w/w) Stearyl alcohol 3.0 (% w/w) White wax 8.0 (% w/w) BASES: BASES EMULSION BASES: According to the type of emulsion, these bases are classified as either W/O or O/W. All W/O emulsions are not water-washable as the oil is in the external phase and O/W emulsions. These are used in dermatological preparations and cosmetic creams. BASES: BASES WATER REMOVABLE BASES: Water - removable bases are basically oil - in - water emulsions. Unlike hydrocarbon and absorption bases, a large proportion of aqueous phase can be incorporated into water - removable bases with the aid of suitable emulsifying agents. BASES: BASES WATER REMOVABLE BASES: It is easy to remove these bases from the skin due to their hydrophilic nature. Hydrophilic ointment USP is an example of a water - removable ointment base. BASES: BASES WATER REMOVABLE BASES: The water-removable bases form a semi permeable film on the site of application after the evaporation of water. As such, the base consists of three component parts: the oil phase, the emulsifier, and the aqueous phase. BASES: BASES WATER REMOVABLE BASES: A typical example of water removable bases is Hydrophilic ointment, USP. Hydrophilic ointment, USP Stearyl alcohol 25.0 (% w/w) White petrolatum 25.0 (% w/w) Methylparaben 0.025(% w/w) Propylparaben 0.015 (% w/w) Sodium lauryl sulfate 1.0 (% w/w) Propylene glycol 12.0 (% w/w) Purified water 37.0 (% w/w) BASES: BASES WATER SOLUBLE BASES: Water - soluble bases do not contain any oily or oleaginous phase. Solids can be easily incorporated into these bases. They may be completely removed from the skin due to their water solubility. BASES: BASES WATER SOLUBLE BASES: These bases contain only water-soluble components. Water-soluble bases are also referred to as greaseless because of a lack of oleaginous materials. Incorporation of aqueous solutions is difficult because they soften greatly with the addition of water. BASES: BASES WATER SOLUBLE BASES: They are better used for non-aqueous or solid substances. Polyethylene glycols (PEG) make up the majority of components of the water-soluble base. BASES: BASES WATER SOLUBLE BASES: PEGs may exist as liquids or waxy solids, identified by numbers that are an approximate indication of their molecular weight. The lowest number signifies a liquid state, which transitions to a waxy solid state as the numbers increase. For example, PEG 400 is a liquid, whereas PEG 4000 is a waxy solid. IDEAL EMULSIFIER: IDEAL EMULSIFIER Ideal properties of emulsifier includes, a) Must reduce surface tension for proper emulsification. b) Prevents coalescence should quickly absorb around the dispersed phase. c) Ability to increase the viscosity at low concentration. d)Effective at low concentration. IDEAL EMULSIFIER: IDEAL EMULSIFIER ANIONIC EMULSIFIERS: The active portion of this class of emulsifiers is the anion. In general, these emulsifiers are more acid-stable and permit adjustment of the emulsion pH level to the desirable range of 4.5 and 6.5. Examples: Common examples include sodium lauryl sulfate and soaps such as triethanolamine stearate. IDEAL EMULSIFIER: IDEAL EMULSIFIER CATIONIC EMULSIFIERS: Cationic compounds are highly surface-active but are used less frequently as emulsifiers. The cation portion of the molecule is usually a quaternary ammonium salt including a fatty acid derivative such as dilauryl dimethyl ammonium chloride. IDEAL EMULSIFIER: IDEAL EMULSIFIER NON-IONIC EMULSIFIERS: This class of emulsifiers shows excellent pH and electrolyte compatibility in emulsions, owing to the fact that they do not ionize in solution. Examples: Glyceryl fatty acid esters Sucrose fatty acid esters. IDEAL EMULSIFIER Emulsifier-HLB : IDEAL EMULSIFIER Emulsifier-HLB EMULSIFIER APPLICATION HLB RANGE Antifoaming 1–3 Emulsifiers (w/o) 3–6 Wetting agents 7-9 Emulsifiers (o/w) 8-18 Solubilizers 15-20 Detergents 13-15 Gelling agents: Gelling agents Gelling agents commonly used are, Synthetic macromolecules, Cellulose derivatives, and , Natural gums. Gelling agents: Gelling agents Synthetic macromolecules: The most common member of this type of gelling agents is carbomer. (e.g., carbomer 934), Gelling agents: Gelling agents Cellulose derivatives: Examples: Carboxymethylcellulose, and Hydroxy propylmethyl cellulose. and , Natural gums (e.g., tragacanth). Gelling agents: Gelling agents Natural gums: These substances include gelling agents of natural origin, like gums. Example: Tragacanth. Gelling agents: Gelling agents CARBOMER: Carbomers in particular are high molecular weight water-soluble polymers of acrylic acid cross-linked with allyl ethers of sucrose and/or penta erythritol. The NF contains monographs for six such polymers: carbomers 910, 934, 934P, 940, 941, and 1342. Gelling agents: Gelling agents CARBOMER They are used as gelling agents at concentrations of 0.5–2.0% in water. Carbomer 940 yields the highest viscosity: between 40,000 and 60,000 CP as a 0.5% aqueous dispersion. Depending on their polymeric composition, different viscosities result. Gelling agents: Gelling agents CARBOMER 941 GEL Carbomer 941 0.5 (% w/w) Glycerine 10.0 (% w/w) Triethanolamine 0.5 (% w/w) Water 89.0 (% w/w) Preservative Q.S Gelling agents: Gelling agents CARBOMER 941 GEL Procedure: Water, glycerine , and preservative are mixed and the carbomer added by sprinkling on the surface while constantly mixing at high speed. Triethanolamine is added with slow agitation until a clear viscous gel forms. MANUFACTURE: MANUFACTURE CREAMS: TRITURATION METHOD: Used for finely divided insoluble powder particles or liquids insoluble powder are added by geometric dilution Liquids are added by making well in centre. MANUFACTURE: MANUFACTURE TRITURATION METHOD (contd.): Air pocket formation avoided. Involved the use of glass slab when small quantities are used Mortar and pestle used when we have large quantities. MANUFACTURE: MANUFACTURE CREAMS: LEVIGATION: Incorporation of insoluble coarse particles. Also known as “ Wet grinding ”. insoluble coarse powder is rubbed with molten base or liquid or a semi solid base. MANUFACTURE: MANUFACTURE LEVIGATION (contd.): A considerable shearing force is applied to avoid grittiness. Aseptic conditions should be maintained. All equipment & spatula to be cleaned by ethanol. Melt the fatty base .substances with the highest melting point to be melt first. These bases then cooled to 60°C. MANUFACTURE: MANUFACTURE LEVIGATION (contd.): Temperature of the aqueous phase to be adjusted to 60°C. The disperse phase to be incorporated to the continuous phase at the same temperature. Avoid air pockets & hasty cooling. MANUFACTURE: MANUFACTURE FUSION METHOD: The fusion method is followed when the drugs and other solids are soluble in the ointment bases. The base is liquefied, and the soluble components are dissolved in the molten base. MANUFACTURE: MANUFACTURE FUSION METHOD: The mixture is then allowed to congeal by cooling. Fusion is performed using steam - jacketed vessels or a porcelain dish. MANUFACTURE: MANUFACTURE FUSION METHOD: The congealed mixture is then spatulated or triturated to obtain a smooth texture. Care is taken to avoid thermal degradation of the base or other components during the fusion process. MANUFACTURE: MANUFACTURE Absorption – type creams are prepared by incorporating large quantities of water into hydrocarbon bases with the aid of a hydrophobic emulsifying agent. Water - insoluble drugs are added by mechanical addition or fusion methods. MANUFACTURE: MANUFACTURE Incorporation of water - soluble components is achieved by slowly adding the aqueous drug solution to the hydrophobic base using pill tile and spatula. If the proportion of aqueous phase is larger, inclusion of additional quantities of emulsifier and application of heat may be needed to achieve uniform dispersion. MANUFACTURE: MANUFACTURE MECHANICAL ADDITION: Water - removable creams are basically hydrophilic - type emulsions. They are prepared by fusion followed by a process called mechanical addition approach. Hydrocarbon components are melted together and added to the aqueous phase that contains water - soluble components with constant stirring until the mixture congeals. MANUFACTURE: MANUFACTURE MECHANICAL ADDITION: A hydrophilic emulsifying agent is included in the aqueous phase in order to obtain stable oil - in - water dispersion. Sodium lauryl sulfate is used in the preparation of hydrophilic ointment USP. MANUFACTURE: MANUFACTURE A wide range of machines are available for the large - scale production of creams. Each of these machines is designed to perform certain unit operations, such as milling, separation, mixing, emulsification, and deaeration. MANUFACTURE: MANUFACTURE Creams are produced with the help of low-shear and high-shear emulsifiers. These emulsifiers are used to disperse the hydrophilic components in the, Hydrophobic dispersion phase (e.g., water-in-oil creams) or Oleaginous materials in aqueous dispersion medium (oil-in-water creams). MANUFACTURE: MANUFACTURE Emulsifiers MANUFACTURE: MANUFACTURE Bematek, Fryma, Koruma (Romaco), Lightnin, Moorhouse, and Ross supply various types of emulsifiers. MANUFACTURE: MANUFACTURE GELS: Gels are relatively easier to prepare compare to ointments and creams. In addition to the gelling agent, medicated gels contain drug, antimicrobial preservatives, stabilizers, dispersing agents, and permeation enhancers. MANUFACTURE: MANUFACTURE GELS: 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 the formation of gel. MANUFACTURE: MANUFACTURE ORDER OF MIXING: 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 the drug and additives are also considered. MANUFACTURE: MANUFACTURE ORDER OF MIXING : 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. MANUFACTURE: MANUFACTURE GELLING MEDIUM: Purified water is the most widely used dispersion medium in the preparation of gels. Under certain circumstances, gels may also contain cosolvents or dispersing agents. MANUFACTURE: MANUFACTURE GELLING MEDIUM: A mixture of ethanol and toluene improves the dispersion of ethylcellulose. Dichloromethane and methanol increase the viscosity of hydroxypropyl cellulose dispersions. MANUFACTURE: MANUFACTURE GELLING MEDIUM: Alcohol improves the rheological stability of polyethylene oxide gels. Inclusion of glycerin, propylene glycol, sucrose, and alcohol improves the dispersion of sodium alginate dispersions. MANUFACTURE: MANUFACTURE PROCESSING CONDITIONS: 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. MANUFACTURE: MANUFACTURE PROCESSING CONDITIONS: 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 form gels at weakly acidic or near - neutral pH conditions (pH 5 – 8). MANUFACTURE: MANUFACTURE PROCESSING CONDITIONS: Gelling agents such as carboxymethyl cellulose sodium, hydroxypropylmethyl cellulose, and sodium alginate form gels over a wide pH range (4 – 10). Hydroxyethyl cellulose forms gel at alkaline pH condition. MANUFACTURE: MANUFACTURE 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. MANUFACTURE: MANUFACTURE 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. MANUFACTURE: MANUFACTURE 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 agents. MANUFACTURE: MANUFACTURE REMOVAL OF ENTRAPPED AIR: In large-scale production, vacuum vessel deaerators are used to remove the entrapped air. PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS An ideal container should protect the product from the external atmosphere such as heat, humidity, and particulates, be nonreactive with the product components, and be easy to use, light in weight, and economic. PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS PACKAGING OF CREAMS: As tubes made of aluminum and plastic meet most of these qualities, they are extensively used for packaging semisolids. Aluminum tubes with special internal epoxy coatings are commercially available for improving the compatibility and stability of products. PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS PACKAGING OF CREAMS: Various modified plastic materials are used for making ointment tubes. Tubes made of low - density polyethylene (LDPE) are generally soft and flexible and offer good moisture protection. PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS PACKAGING OF CREAMS: Tubes made of high - density polyethylene (HDPE) are relatively harder but offer high moisture protection. PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS PACKAGING OF CREAMS: Polypropylene containers offer high heat resistance. Plastic containers made of polyethylene terephthalate (PET) are transparent and provide superior chemical compatibility PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS PACKAGING OF CREAMS: A recent method known as blow fill sealing (BFS) performs fabrication of container, filling of product, and sealing operations in a single stage and hence is gaining greater attention. PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS PACKAGING OF CREAMS: The products can be sterile filled, which makes BFS a cost - effective alternative for aseptic filling. All plastic materials are suitable for BFS processing. PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS PACKAGING OF CREAMS: As the container is formed inside the BFS machine, upstream handling problems are avoided. The BFS machine can hand the container off to any secondary packaging operation that needs to be performed. PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS PACKAGING OF CREAMS: Typically a secondary overwrap is added to the containers prior to cartooning. An additional advantage of BFS containers is the integrated design of the applicator into the product container. PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS PACKAGING OF GELS: Being viscous and non - Newtonian systems, gels need high attention during packing into containers. Usually they are packed into squeeze tubes or jars made of plastic materials. PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS PACKAGING OF GELS: Aluminum containers are also used when the product pH is slightly acidic. Pump dispensers and prefilled syringes are sometimes used for packing gels. PACKAGING OF SEMISOLIDS: PACKAGING OF SEMISOLIDS PACKAGING OF GELS: As most of the gels contain an aqueous phase, preservation in airtight containers helps in protecting them from microbial attack. Usually they are preserved at room temperature and protected from direct sunlight and moisture. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS EVALUATION OF CREAMS: MINIMUM FILL TEST: This test is performed to compare the weight or volume of product filled into each container with their labeled weight or volume. It helps in assessing the content uniformity of product. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS MINIMUM FILL TEST: A minimum - fi ll test is applied only to those containers that contain not more than 150 g or mL of preparation. It is performed in two steps. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS MINIMUM FILL TEST: Initially, labels from the product containers are removed. After washing and drying the surface, their weights are recorded ( W1 ). In the second step, the entire product from each container is removed. After cleaning and drying, the weight of empty containers is recorded ( W2 ). EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS MINIMUM FILL TEST: The difference between total weight ( W1 ) and empty - container weight ( W2 ) gives the weight of product. The USP recommends that the average net content of 10 containers should not be less than the labeled amount . EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS MINIMUM FILL TEST: If the product weight is less than 60 g or mL, the net content of any single container should not be less than 90% of the labeled amount. If the product weight is between 60 and 150 g or mL, the net content of any single container should not be less than 95% of the labeled amount. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS MINIMUM FILL TEST: If these limits are not met, the test is repeated with an additional 20 containers. All semisolid topical preparations should meet these specifications. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS WATER CONTENT TEST: The presence of minor quantities of water may alter the microbial, physical, and chemical stability of ointments and creams. Titrimetric methods are usually performed for determining the water content in these preparations. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS WATER CONTENT TEST: These methods are based on the quantitative reaction between water and anhydrous solution of sulfur and iodine in the presence of a buffer that can react with hydrogen ions. Special titration setups and reagents (Karl Fischer, KF) are used in these determinations. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS MICROBIAL SCREEING: Semisolid preparations are required to be free from any microbial contamination. Hence, most of the topical ointments are screened for the presence of Staphylococcus aureus and Pseudomonas aeruginosa . EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS MICROBIAL SCREEING: In some cases, screening for Escherichia coli, Salmonella species, and total aerobic microbial counts is recommended by the USP. For instance, clobetasol propionate ointment USP and mometasone furoate ointment USP are screened for all these organisms. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS EVALUATION OF GELS: Some of the tests recommended by the USP for gels include, Minimum fill, pH, Viscosity, Microbial screening. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS EVALUATION OF GELS: pH: Many gelling agents show pH - dependent gelling behavior. They show highest viscosity at their gel point. Determination of pH is therefore important to maintain consistent quality. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS pH: Conventional pH measurements are difficult. They may often give erratic results. Hence special pH electrodes are used for viscous gels. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS pH: Some commercially available pH measurement systems for semisolid Formulations are, Flat - surface digital pH electrodes from Crison. Combination pH puncture electrodes with spear - shaped tip from Mettler. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS pH: Combination electrodes that contain a built - in temperature probe, a bridge electrolyte chamber and movable sleeve junction from Mettler. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS VISCOSITY: Viscosity measurement is often the quickest, most accurate, reliable method to characterize gels. It gives an idea about the ease with which gels can be processed, handled, or used. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS VISCOSITY: Cup - and - bob viscometers and cone - and - plate viscometers are widely used for viscous liquids and gels. They measure the frictional force that is created when gels start flowing. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS VISCOSITY: These viscometers are usually calibrated with certified viscosity standards before each measurement. General - purpose silicone fluids which are less sensitive to temperature change are used as standards. EVALUATION OF SEMISOLIDS: EVALUATION OF SEMISOLIDS VISCOSITY: Commercially available viscometers include, Brookfi eld rotational viscometers, Haake rheometers, Schott viscoeasy rotational viscometers, Malvern viscometers, and Ferranti - Shirley cone-and-plate viscometers. COMMERCIAL PRODUCTS: COMMERCIAL PRODUCTS CREAMS: BECLOMETHASONE AND NEOMYCIN AND CLOTRIMAZOLE CREAM INDICATIONS : Eczema, Psoriasis, Otitis, Externa, Lichen, Simplex & Planus , Anal & Vulval Pruritus,Contact Dermatitis. Composition: Beclomethasone Dipropionate Neomycin Sulphate Clotrimazole COMMERCIAL PRODUCTS: COMMERCIAL PRODUCTS CREAMS: Compound Ketoconazole Cream(OEM/OBM) Indications: mycotic infection of skin : tinea manuum , athlete's foot, tinea corporis, tinea cruris. COMMERCIAL PRODUCTS: COMMERCIAL PRODUCTS CREAMS: Zovirax cream (aciclovir) Contains: Aciclovir BP ....... 5% w/w Manufacturer: GSK (Glaxo Smith Kline) COMMERCIAL PRODUCTS: COMMERCIAL PRODUCTS CREAMS: Betamethasone dipropionate. Anti –inflammatory Indications: Eczema, dermatitis, allergies, and rash. COMMERCIAL PRODUCTS: COMMERCIAL PRODUCTS GELS: Benzocaine Local anesthetic In mouth to relieve pain or irritation caused by many conditions. COMMERCIAL PRODUCTS: COMMERCIAL PRODUCTS GELS: Desoximetasone Anti - inflammatory Eczema, dermatitis, allergies, and rash. COMMERCIAL PRODUCTS: COMMERCIAL PRODUCTS GELS: Erythromycin Antibiotic Acne and skin infection due to bacteria. COMMERCIAL PRODUCTS: COMMERCIAL PRODUCTS GELS: Fluocinonide Anti - inflammatory Psoriasis, eczema, dermatitis, allergies, and rash. NOVEL ADVANCES AND RECENT DEVELOPMENT: NOVEL ADVANCES AND RECENT DEVELOPMENT CREAMS: Creams containing microspheres: Albumin microsphere containing vitamin A can be administered by using creams topically. 222 ± 25 μm size of microsphere of vitamin A were produced by emulsion method. NOVEL ADVANCES AND RECENT DEVELOPMENT: NOVEL ADVANCES AND RECENT DEVELOPMENT CREAMS: Lamellar faced creams: They are liquid paraffin in water emulsion prepared from cetrimide / fatty alcohol NOVEL ADVANCES AND RECENT DEVELOPMENT: NOVEL ADVANCES AND RECENT DEVELOPMENT CREAMS: Cream containing lipid Nanoparticles: The development of a water-in-oil cream containing small particles of solid paraffin was studied. A high degree of occlusivity was obtained with smooth, flexible films prepared by drying aqueous dispersions of solid paraffin particles with a mean size of 200 nm (nanoparticle dispersion). NOVEL ADVANCES AND RECENT DEVELOPMENT: NOVEL ADVANCES AND RECENT DEVELOPMENT GELS: Controlled release gels: Gel formulations with suitable rheological and mucoadhesive properties increase the contact time at the site of absorption. However, drug release from the gel must be sustained if benefits are to be gained from the prolonged contact time. NOVEL ADVANCES AND RECENT DEVELOPMENT: NOVEL ADVANCES AND RECENT DEVELOPMENT GELS: Some other recent advances in gels being, Extended release gels Bioadhesive Gels Thermosensitive sol-gel reversible hydrogels. REFERENCES: REFERENCES Theory and Practice of Industrial Pharmacy by, Leon Lachman Herbert A. Liebermann. Encyclopedia of PHARMACEUTICAL TECHNOLOGY, Third Edition. Edited by James Swarbrick. Handbook of Pharmaceutical Manufacturing Formulations by Sarfaraz K. Niazi REFERENCES: REFERENCES PHARMACEUTICAL MANUFACTURING HANDBOOK, Production and Processes, by SHAYNE COX GAD.