Lecture 2: Manufacturing of extractive preparations. TINCTURES

Extraction process depends on many factors, most important of which: hydrodynamic conditions surface of separation of phases difference of BAS concentration time of extraction process viscosity of extragent temperature adding of surfactants, nature of extragent, porosity and the size of cavities between pieces of crushed HRM, influence of vibrations, pulsations, electric pulse discharge in a liquid medium.

Extraction

Extraction - as the term is used pharmaceutically, involves the separation of medicinally active portions of plant or animal tissues from the inactive or inert components by using selective solvents in standard extraction procedures. The products so obtained from plants are relatively impure liquids, semisolids or powders intended only for oral or external use.

These include classes of preparations known as: decoctions,infusions,tinctures, fluid extracts, pilular (semisolid) extracts powdered extracts. Such preparations popularly have been called Galenicals, named after Galen, the second century Greek physician.

Solid-phase extraction (SPE) is a separation process by which compounds that are dissolved or suspended in a liquid mixture are separated from other compounds in the mixture according to their physical and chemical properties.

Molecular diffusion- often called simply diffusion, is the thermal motion of all (liquid or gas) particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size (mass) of the particles. Diffusion explains the net flux of molecules from a region of higher concentration to one of lower concentration, but it is important to note that diffusion also occurs when there is no concentration gradient.

Molecular diffusion

Diffusion is part of the transport phenomena. Of mass transport mechanisms, molecular diffusion is known as a slower one. Molecular diffusion is characterized by coefficient of molecular diffusion D, which is derived from the equation of Einstein: D= RT/6Nπrµ

R - universal gas constant, is equal to 8.32 J / (mol deg); N 0 - constant of Avogadro (6, ); T - absolute temperature, K; µ - viscosity of solution, N s/m2; r - radius of Diffusing particles, m. r - radius of Diffusing particles, m. D= RT/6Nπrµ

Coefficient of molecular diffusion describes the ability of a given substance to penetrate due to diffusion in the stationary environment. As seen from equation, they is increased with increasing of temperature and decreased with increasing viscosity of medium and particle size of BAS molecules. D= RT/6Nπrµ

Layer of extragent is present about the wall of part of HRM. It called diffusion boundary layer, on the surface of slices of HRM. This layer makes a great resistance to further transfer of extracted substances in the extragent. Its thickness depends on the hydrodynamics of the process, especially rate of mixing during extraction. If the mixing speed is higher, the boundary layer is thinner.

First law of Fiks expresses transferring of substances within the diffusion boundary layer : S=βF (C 1 -C 2 )τ/dl S=βF (C 1 -C 2 )τ/dl S – amount of substances that is diffused, kg; β – coefficient of convective diffusion, m/s; F - surface of separation phases, m 2 ; d - thickness of diffusion boundary layer, m; τ - time of diffusion, s; C 1 - C 2 – difference of concentration of BAS, kg/m 3 ; l – thickness of HRM part throw which BAS are diffused.

Tinctures are referred to galenicals obtained by extraction of plant raw material (crude drugs) with an appropriate solvent. The main object of manufacturing process is separation of the soluble principles from drugs by treating them with a liquid capable of dissolving them, which is called the menstruum or extragent.

Tinctures – is a liquid alcohol or water-alcohol extract are obtained from dried or fresh plant or animal raw materials, while production of which heat and remove of the solution for extraction are not carried out. At the manufacture of tinctures from 1 mass part of PRM you can produce 5 volume parts of finished product, from a potent drug – 10 parts.

Advantages of tinctures Ethanol is able to dissolve substances which are less soluble in water, while at the same time the water content can dissolve the substances less soluble in ethanol. Ethanol is able to dissolve substances which are less soluble in water, while at the same time the water content can dissolve the substances less soluble in ethanol. It is possible to vary the proportion of ethanol and water to produce tinctures with different qualities because of different substances. It is possible to vary the proportion of ethanol and water to produce tinctures with different qualities because of different substances. The solvent also acts as a preservative. The solvent also acts as a preservative.

Tinctures Simple Complex are derived from one type of HRM mixture of extracts from several plants, sometimes with the addition of drugs

Methods obtaining of tinctures Maceration and its improved types Percolation Dissolution of soft and dry extracts

Maceration This method of tinctures production is officially used in the case of resins, balsams, gums, soap, etc., where the practical difficulties likely to be encountered in percolation would offset any advantages that the latter process might possess.

Stages of the maceration: 1. Loading of crushed PRM with the prescribed volume of extragent in the tank for maceration and allowed to stand at room temperature 15 – 20 °C, with frequent agitation. If there are not special instructions, the infusion continues during 7 days. 2. The mixture then is strained, the marc (the damp solid material) is pressed, washing raw by a small volume of extragent, wring out again. 3. Flowing together all infusions and communicating by solution for extraction to the desired volume. 4. The combined liquids are clarified by filtration or decantation after standing.

Disadvantages of maceration: this method is slow, raw material is not fully exhausted. Methods of intensify of the maceration: 1. Repeated maceration (bismaceration) 2. Maceration with forced circulation of extragent 3. Vortex extraction (turboextraction) 4. Ultrasound maceration 5. Maceration in the medium of milling (bolls mill and rotating pulsation apparatus are used)

Repeated maceration may be more efficient than a single maceration, since an appreciable amount of active principle may be left behind in the first pressing of the marc. The repeated maceration is more efficient in cases where active constituents are more valuable. Double maceration is used for concentrated infusions which contain volatile oil, e.g.

Bismaceration or repeated maceration. Dividing of the total volume of the extragent on 3 or 4 parts and successively infusing of the PRM with each parts of the menstruum. Each time the extracts are poured out and flowed together.

Maceration with circulation of the extragent. It is performed in the tank 1 for maceration with a perforated bottom 3, on which there is the filter material 2. 4 – pump.

Solution for extraction (extragent) is smoothed through PRM which is on perforated bottom by the pump (4) for the several times to achieve of the equilibrium.

Vortex extraction or turboextraction, is based on using of turbine stirrer which is rotates with speed about 8000 – times for 1 minute. Turbine stirrer causes very intensive mixing of raw material with the extragent and crushing of raw material. Extraction time is shortened to 10 min.

Ultrasonic extraction. The procedure involves the use of ultrasound with frequencies ranging from 20 kHz to 2000 kHz; this increases the permeability of cell walls and produces cavitation. Source of ultrasound is attached to the body of the tank and immersed in the medium of the extraction. Pressure with variable, cavitation and "wind sound“ are created due ultrasound.

Digestion  is the form of maceration which consists in the application of a gentle heat to the substance which is being treated.  It is used in those cases where a moderately elevated temperature is unobjectionable; the heat increases the solvent powers of the menstruum.  If the solvent or menstruum is volatile it is necessary to attach a reflux condenser to the vessel in which the lotion is being conducted so that the solvent may be recovered and returned.

Percolation (from Lat. Rer c olatio - filtering through) is the method obtaining of extracts while simultaneous loading of the extragent and pouring out of the extract. Stages of the Percolation: 1. Moistening of plant raw material (swelling materials), 4- 8 hours 2. Infusion, hours 3. Obtaining the extract by simultaneous loading the extragent and pouring out of the extract. Percolator (a narrow, cone shaped vessel open at both ends) is used.

Percolators

Moistening The solid ingredients are moistened with an appropriate amount of the specified menstruum and allowed to stand for approximately 4 h in a wellclosed container, after which the mass is packed and the top of the percolator is closed.

Infusion Additional menstruum is added to form a shallow layer above the mass, and the mixture is allowed to macerate in the closed percolator for h. Raw material is poured over with the extragent to creation a "mirror” - thickness layer of solution above the raw material which should be mm

Obtaining tinctures The inlet and outlet of the percolator are opened and the liquid contained therein is allowed to drip slowly and additional menstruum is added as required, until the percolate measures about three-quarters of the required volume of the finished product. The mixed liquid is clarified by filtration or by standing followed by decanting.

Obtaining of infusing by percolation continuous passage of extragent through the layer of raw material and the collection of the extract. At the same time pouring out of the extract and loading of extragent from top on PRM are conducted at speeds 1 / 24 or 1 / 48 (for large enterprises) of working volume of percolator for 1 hour. Extract is forced from PRM by flow of fresh extragent, and difference of concentration of BAS is create in PRM and in extragent. Percolations rate should be such that diffusion of extractive BAS in the extract has enough time.

The success of the process of percolation largely depends on the regulation of the flow of the percolate; if this is too rapid, incomplete exhaustion will result, but if too slow, valuable time is wasted and considerable loss of menstruum occurs from evaporation. For fluid extracts using 1000 Gm. of powder, and rate of flow should not exceed 10 drops a minute; for official quantities of tinctures and preparations of about the same strength, 20 drops a minute

Purification of extracts Extracts are a muddy liquid, containing a significant amount of suspended particles. Extracts are clear by standing at above 10 °C to obtain of a transparent liquid. After standing more than 2 days they era filtered by decantation (without shaking sediment). Filterpress, Drook filters, Nootch filters, centrifuges are used for filtration.

Dissolution of soft or dry extracts 1. Calculated amount of dry or soft extract is dissolved in alcohol with required concentration in a reactor with stirrer. 2. The obtained tinctures are filtered. This method is characterized by a significant reduction in the time of tinctures obtaining. It is very simple, are used small number of equipment.

Quality control: 1. Appearance. Color, odor, opacity of the tincture are to be tested. 2. Relative density Where applicable, the tincture complies with the limits prescribed in the monograph. 3. Ethanol content The ethanol content complies with that prescribed. It's determined by distillation method. 4. Methanol and 2-propanol Not more than 0.05 per cent. 5. Dry residue Where applicable, the tincture complies with the limits prescribed in the monograph. 6. Identity. This test is carried out by chemical reactions (assays) and by chromatography 7. Quantitative determination of BAS. 8. Heavy metals. Not more than 0.001%. 9. Microbiological purity.