Lecture 5: Pharmaceutical Extraction Methods PDF

Outline Summary of last lecture Methods of extraction Other pharmaceutical preparations prepared by extraction processes Clarification; principles, methods and applications Summary & discussion Department of Pharmacy /Al...

Outline Summary of last lecture Methods of extraction Other pharmaceutical preparations prepared by extraction processes Clarification; principles, methods and applications Summary & discussion Department of Pharmacy /Al-Kunooze University College 2  Methods of extraction Maceration Percolation Decoction Digestion Infusion Department of Pharmacy /Al-Kunooze University College 3  Maceration The term maceration comes from the Latin ‘macerare’ meaning ‘to soak’. It is a process in which the properly comminuted drug is permitted to soak in the menstruum with shaking until the cellular structure is softened and penetrated by the menstruum and the soluble constituents are dissolved. An alternative to repeated shaking is to place the drug in a porous cloth bag that is tied and suspended in the upper portion of the menstruum, “ the same as a tea bag is suspended in water to make a cup of tea”. Maceration is usually conducted at a temperature of 15°C to 20°C for 3 days or until the soluble matter is dissolved. Department of Pharmacy /Al-Kunooze University College 4  Maceration In the maceration process, the drug to be extracted is generally placed in a wide-mouth container with the prescribed menstruum, the vessel is stoppered tightly, and the contents are agitated repeatedly over a period usually ranging from 2 to 14 days. The agitation permits the repeated flow of fresh solvent over the entire surface area of the comminuted drug. Department of Pharmacy /Al-Kunooze University College 5  Percolation The term percolation, from the Latin ‘per’ meaning through, and ‘colare’ meaning to strain, may be described generally as a process in which a comminuted drug is extracted of its soluble constituents by the slow passage of a suitable solvent through a column of the drug. The drug is packed in a special extraction apparatus termed a percolator, with the collected extractive called the percolate. Department of Pharmacy /Al-Kunooze University College 6  Percolation In the process of percolation, the flow of the menstruum over the drug column is generally downward to the exit orifice, drawn by the force of gravity as well as the weight of the column of liquid. In certain specialised and more sophisticated percolation apparatus, additional pressure on the column is exerted with positive air pressure at the inlet and suction at the outlet or exit. Department of Pharmacy /Al-Kunooze University College 7  Percolation Percolators for drug extraction vary greatly as to their shape, capacities, composition, and utility. Percolators employed in the large-scale industrial preparation of extractives are generally stainless steel or glass-lined metal vessels that vary greatly in size and operation. Percolators used to extract leaves may be 6 to 8 ft in diameter and 12 to 18 ft high. Department of Pharmacy /Al-Kunooze University College 8  Percolation Percolation on a small scale generally involves the use of glass percolators of various shapes for extraction of small amounts (up to 1 kg) of crude drug. The shapes of percolators in common laboratory and small-scale use are: 1. Cylindrical 2. Roundish 3. Conical or funnel shaped Each type has a special utility in drug extraction. Department of Pharmacy /Al-Kunooze University College 9  Percolation The cylindrical percolator is particularly suited to the complete extraction of drugs with a minimal expenditure of menstruum. By the passage of the menstruum over the drug contained in a high, narrow column (rather than in a lower, wider column), each drug particle is more repeatedly exposed to the passing solvent. A funnel-shaped percolator is useful for drugs that swell during maceration, because the large upper surface permits expansion of the drug column with little risk of a too tightly packed column or breakage of a glass percolator. Department of Pharmacy /Al-Kunooze University College 10  Infusion This method involves the placement of plant material in water, then boiling the mixture for about 15 minutes, followed by filtration to obtain the extracted material and removing the marc. Digestion Maceration with continued heating during the maceration period. The temperature is usually maintained between 40 ˚C – 60 ˚C. Decoction Involves first macerating the drug with cold water, followed by the addition of boiling water in an amount equals to 90 % of the desired volume. Department of Pharmacy /Al-Kunooze University College 11  Other pharmaceutical preparations prepared by extraction processes Fluidextracts Fluidextracts are liquid preparations of vegetable drugs prepared by percolation. They contain alcohol as a solvent, preservative, or both and are made so that each mL contains the therapeutic constituents of 1 g of the standard drug they represent. Department of Pharmacy /Al-Kunooze University College 12  Do you think that fluidextracts are commonly used in practice or not and why? Department of Pharmacy /Al-Kunooze University College 13  Fluidextracts Because of their concentrated nature, many fluidextracts are considered too potent to be safely self-administered, and their use is almost nonexistent in medical practice. Many fluidextracts are simply too bitter tasting or unpalatable to be accepted by the patient. Therefore, most fluidextracts are either modified by the addition of flavouring or sweetening agents before use or used as the drug source of other liquid dosage forms, such as syrups. Department of Pharmacy /Al-Kunooze University College 14  Official examples of fluidextracts Senna Fluidextract N.F. (cathartic) Cascara Sagrada Fluidextract U.S.P. (cathartic) Liquorice Fluidextract N.F. (flavoring agent) Note: fluidextracts should be stored in tightly closed containers and protected from light! Why? Department of Pharmacy /Al-Kunooze University College 15  Extracts Extracts are concentrated preparations of vegetable or animal drugs obtained by removal of the active constituents of the respective drugs with suitable menstrua, evaporation of all or nearly all of the solvent, and adjustment of the residual masses or powders to the prescribed standards. Department of Pharmacy /Al-Kunooze University College 16  Extracts Extracts are potent preparations, usually between two and six times as potent on a weight basis as the crude drug. They contain primarily the active constituents of the crude drug, with a great portion of the inactive constituents and structural components of the crude drug having been removed. Their function is to provide in small amounts and in convenient, stable physical form the medicinal activity and character of the bulkier plants that they represent. They are normally used in pharmaceutical products formulation. Department of Pharmacy /Al-Kunooze University College 17  Extracts In the manufacture of most extracts, percolation is employed to remove the active constituents from the drug, with the percolates generally being reduced in volume by distillation under reduced pressure to reduce the degree of heat and to protect the drug substances against thermal decomposition. Department of Pharmacy /Al-Kunooze University College 18  Extracts Extracts are made in three forms: 1. Semiliquid extracts or those of a syrupy consistency prepared without the intent of removing all or even most of the menstruum, 2. Solid extracts of a plastic consistency prepared with nearly all of the menstruum removed, and 3. Powdered extracts prepared to be dry by the removal of all of the menstruum. The pilular (solid) extract is preferred in compounding a semisolid dosage form such as an ointment or paste, whereas the powdered form is preferred in the compounding of such dosage forms as powders, capsules, and tablets. Department of Pharmacy /Al-Kunooze University College 19  Example of extracts Belladonna Extract U.S.P.: Each 100 g contains 1.15-1.35 g of the alkaloids of belladonna leaves. It may be in the form of a firm extract (Pilular Belladonna Extract) or a dry extract (Powdered Belladonna Extract). Department of Pharmacy /Al-Kunooze University College 20  Resins Natural resins are solid or semisolid exudations from plant or from insects feed on plants. Chemically, these exudations are oxidised terpenes of the volatile oils of the plants. Prepared resins are produced exhaustive percolation of a plant having a resin as the major ingredient using alcohol as solvent. Example: Podophyllum resin USP: It has an antimitotic action and is used principally as a topical treatment for anogenital warts. It is applied as a 15% (Indian podophyllum) or up to a 25% solution (American podophyllum) Department of Pharmacy /Al-Kunooze University College 21  Oleoresins They are mixture of volatile oils and resins. They are prepared by percolation using selective solvent “usually alcohol, ether or acetone”. Example: Capsicum Oleoresin U.S.P. An alcoholic extract of the dried ripe fruits of Capsicum. It contains not less than 8% of total capsaicins. It is a dark red oily liquid, soluble in alcohol, acetone, chloroform, ether, and volatile oils. It is used externally as a counter-irritant. Capsaicin, the active ingredient of capsicum, is also used in topical preparations in the treatment of painful skin conditions. Department of Pharmacy /Al-Kunooze University College 22  Clarification Clarification is a term used to describe processes that involve the removal or separation of a solid from a fluid, or a fluid from another fluid. Department of Pharmacy /Al-Kunooze University College 23  What are the reasons for using clarification in the field of pharmaceutics generally and during solution preparation? Department of Pharmacy /Al-Kunooze University College 24  Clarification In pharmaceutical processing there are two main reasons for clarification processes, these include: To remove unwanted solid particles from either a liquid product or from air, To collect the solid as the product itself (e.g. following crystallisation) Department of Pharmacy /Al-Kunooze University College 25 There are different techniques to achieve clarification. What are the parameters that decide which one is the most suitable method? Department of Pharmacy /Al-Kunooze University College 26 The parameters that decide the most suitable method of clarification 1. The particle size of the suspended matter 2. The physical state of the suspended matter 3. The quantity of the suspended matter 4. The characteristics of the fluid medium 5. The speed of operation Department of Pharmacy /Al-Kunooze University College 27 What are the principle operations used to achieve clarification? Department of Pharmacy /Al-Kunooze University College 28 Methods of clarification Settling Filtration Absorption and adsorption Department of Pharmacy /Al-Kunooze University College 29 1) Settling It is the simplest method of clarification. It is done by allowing the liquid to stand in a suitable container until the suspended matter is settled down or risen to the top of the liquid. Department of Pharmacy /Al-Kunooze University College 30 1) Settling Acceleration of settling can be done by centrifugation. In this process the liquid is rotated in a special container at high speed. The device used for centrifugation is called centrifuge. The centrifugal forces developed inside the centrifuge drive the suspended particles to the bottom and sides of the device. Department of Pharmacy /Al-Kunooze University College 31 1) Settling c=2.01 x dn2 where: c: centrifugal effect d: diameter of rotation n: speed of rotation. The effective force “centrifugational effect” is proportional to the square of speed of rotation and may be several thousand times as the gravitational force involved in natural settling. Department of Pharmacy /Al-Kunooze University College 32  2) Filtration Filtration is the process by which the suspended matter is removed from fluid by passing the mixture through porous, fibrous or granular substances. Department of Pharmacy /Al-Kunooze University College 33 2) Filtration Filtration can be classified into the following categories depending on the physical state of the suspended matter and medium: a. Solid-liquid filtration b. Solid-gas filtration c. Liquid-liquid filtration d. Liquid-gas filtration Department of Pharmacy /Al-Kunooze University College 34  Give examples “applications” for each type of filtration mentioned previously? Homework Department of Pharmacy /Al-Kunooze University College 35  What are the factors that affect the rate of filtration? Department of Pharmacy /Al-Kunooze University College 36 Factors affecting the rate of filtration Department of Pharmacy /Al-Kunooze University College 37  Factors affecting the rate of filtration The rate of filtration (volume of filtered material (V, m3) obtained in unit time (t, s) depends on the following factors: The area available for filtration (A, m2), which in this case is the cross-sectional area of the funnel, The pressure difference (∆P, Pa) across the filter bed (filter medium and any cake formed), The viscosity of the fluid passing through the filter, i.e. the filtrate (Pa s), The thickness of the filter medium and any deposited cake (L, m). Department of Pharmacy /Al-Kunooze University College 38 Factors affecting the rate of filtration The above factors are combined in the Darcy’s equation: Department of Pharmacy /Al-Kunooze University College 39  Factors affecting the rate of filtration The proportionality constant K (m2) expresses the permeability of the filter medium and cake and will increase as the porosity of the bed increases. where: k : the permeability of the filter medium and cake e : the porosity of the filter medium and the cake s : the surface area of the particles comprising the cake Department of Pharmacy /Al-Kunooze University College 40  Filter Media The filter medium used for clarification must have the following properties:  Capable of delivering a clear filtrate at suitable production rate It must withstand the mechanical stress which may be imposed on it without rupturing or being compressed significantly. No chemical or physical interactions with the components of the filtrate should occur. Department of Pharmacy /Al-Kunooze University College 41  Types of Filter Media 1. Depth filters 2. Membrane filters Department of Pharmacy /Al-Kunooze University College 42 Depth filters Depth filters retain suspended matter within the depth of the filter matrix. In this case, suspended particles have to move through the tortuous path of the fiber matrix and eventually will collide with a fiber and separate from the medium. Due to the depth retention, such filters have a very high load capacity and are able to separate a high load of suspended matter of different sizes. Department of Pharmacy /Al-Kunooze University College 43 Depth filters Depth filter are fibrous materials: for example, polypropylene, borosilicate, or glassfibre materials. Borosilicate and glassfibre materials are highly adsorptive and commonly used to remove colloidal substances, like iron oxide from water or colloidal particles from sugar solutions. SEM of the random fiber matrix of a depth filter Department of Pharmacy /Al-Kunooze University College 44 Membrane Filters Membrane filters are surface retentive filters and, therefore, have the distinct disadvantage to clog faster. In comparison to depth filters, membrane filters have a narrow pore size distribution, which results in a sharper retention rate. Another advantage of membrane filters is the fact that these are integrity testable. Therefore, defects can be detected, which is critical, due to the function of membrane filters, mainly in separating microorganisms from pharmaceutical solutions ‘sterilization’. Department of Pharmacy /Al-Kunooze University College 45 Membrane Filters Membrane filters are made in a wide variety of pore sizes. The effective pore size for membranes vary, and membranes can be used in reverse osmosis (RO), nanofiltration (NF), ultrafiltration (UF), and microfiltration (MF). Q: what are the particle size ranges for each one of the techniques mentioned above? Department of Pharmacy /Al-Kunooze University College 46 Examples of Membrane Filters Filter fabrics: They are commonly woven from natural fibers such as cotton and from synthetic fibers and glass. Examples: Cotton fabric which is most common and widely used as a primary medium. Nylon is often superior for pharmaceutical use, since it is unaffected by molds, fungi, or bacteria; provides extremely smooth surface for good cake discharge; and has negligible absorption properties. Teflon is superior for most liquid filtrations because it is almost chemically inert, provides sufficient strength and can withstand elevated temperature. Department of Pharmacy /Al-Kunooze University College 47  Examples of Membrane Filters Porous structure of cellulose acetate membrane Department of Pharmacy /Al-Kunooze University College 48 Filter Aids They are special type of filter media that forms a fine surface deposit that screens out all solids and preventing them from contacting and plugging the supporting filter medium. Usually, the filter aid acts by forming a highly porous, and non-compressible cake that retains solids as does any depth filter. Filter aids are insoluble adsorbent materials that may be added to liquid prior to its filtration to increase the efficiency of filtration. Department of Pharmacy /Al-Kunooze University College 49 Filter Aids These filter aids can be used in two different ways: 1. They can be used as a precoat before the slurry is filtered. This will prevent solids from plugging the filter medium and also give a clearer filtrate. 2. They can also be added to the slurry before filtration. This increases the porosity of the cake and reduces resistance of the cake during filtration. Note : the use of filter aids is usually limited to cases where the cake is discarded or where the precipitate can be separated chemically from the filter aid. Department of Pharmacy /Al-Kunooze University College 50  The characteristics of filter aid It should have a structure that permits the formation of porous and non-compressible cake It should have a particle size distribution suitable for the retention of solids as required It should be able to remain suspended in the liquid to be filtered It should be free of impurities It should have high adsorption capacity It should be inert to the liquid being filtered It should be free of moisture in cases where the addition of moisture to the liquid is undesirable. Department of Pharmacy /Al-Kunooze University College 51  Examples of filter aids Purified talc Diatomite Charcoal Perlite Department of Pharmacy /Al-Kunooze University College 52  3) Absorption and adsorption Filter media can affect clarification through absorption and adsorption processes in addition to their sieving effect. In absorption, the foreign particles are trapped within the medium, while in adsorption, the foreign substances adhere to the surface of the media. Frequently, filter aids provide the absorption and adsorption functions. Department of Pharmacy /Al-Kunooze University College 53