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HERBAL DRUGS

          Herbal drugs are mainly whole, fragmented or cut, plants, parts of plants, algae, fungi, lichens, some of which are also derived from animal or mineral sources. They are usually in dried forms, but sometimes fresh, and also including certain unprocessed plant exudates. Herbal drugs are precisely defined by their scientific name (genus, species,variety and author).

          Production Herbal drugs are obtained from natural or cultivated/domesticated origins. Suitable collection, cultivation, harves ting, drying, fragmentation and storage conditions are essential to guarantee the quality of herbal drugs.

          Herbal drugs are, as far as possible, free from impurities such as soil, dust, dirt and other contaminants such as fungal, insect and other animal contaminations

          If a decontaminating treatment has been used, it is necessary to demons trate that the constituents of the plant are not affected and that no harmful residues remain.

          Foreign matter Where applicable, the herbal drugs comply with the limits prescribed in the monograph.

          Pesticide residues Herbal drugs comply with the “Pesticide Residues” (Appendix 7.22H) taking into account the nature of the plant, where necessary the preparation in which the plant might be used, and where available the knowledge of the complete record of treatment of the batch of the plant.

          Loss on drying or Water Where applicable, the herbal drugs comply with the limits prescribed in the monograph. A determination of water is carried out for herbal drugs with a high volatile oil content.

           Heavy metals See under Arsenic and Heavy Metals in the General Notices of the Thai
Herbal Pharmacopoeia.

          Microbial limit The products consis ting of herbal drugs comply with the “Limits for Microbial Contamination” (Appendix 10.5).

          Packaging and storage Herbal drugs should be kept in well-closed containers, protected from light.

CAPSULES

          This appendix should be read in conjunction with Appendix 1.16 under Capsules. 
          Capsules are solid dosage forms with hard or soft shells.The different categories of capsules that exist include hard, soft and delayed-release capsules (enteric capsules). Hard capsules and delayed-release capsules contain crude drug powder or crude drug extract(s) or a combination of both, all with or without suitable excipient(s). Soft capsules usually contain crude drug extract(s), with or without suitable excipients(s).

          Disintegration Capsules comply with the “Disintegration Test for Tablets and Capsules” (Appendix 4.23).

          Weight variation Weigh individually ten capsules. Open each capsule without losing anypart of the shell and remove the contents as completely as possible. For hard capsules, clean the shell with a small brush. For soft capsules, wash the shell with ether or other suitable solvent and allow to s tand until the odour of the solvent is no longer perceptible. Weigh the shell. The weight of the contents in each capsule is the difference between the weighings.

          Compare the weight of the contents in each capsule with the labelled weight or with the average weight for the capsules in which assay required or no labelled weight stated. Unless otherwise directed in the monograph, not more than two of the individual weights deviate from the labelled weight or the average weight by more than the percentage deviation of 10 per cent and none deviates by more than twice that percentage.

EXTRACTS

          Extracts are liquid (liquid extracts), semi-solid (soft extracts and oleoresins) or solid (dry extracts) preparations, obtained from herbal drugs. The constituents of interest are completely or partially separated from other components with the aid of water, ethanol or other suitable solvents. 

          For this Pharmacopoeia, the solvents preferred are ethanol, water or ethanol-water mixtures. In case of other solvents being used, the test for residual solvents shall be demonstrated by the acceptable validated methods. This extraction process involves the removal of the desired constituents from the herbal matter with suitable menstrua, the evaporation of all or nearly all of the solvent, and the adjustment of the residual fluids, masses, or powders to the prescribed standards. Extracts may be subjected to processes that increase the content of characterized constituents, decrease the content of unwanted constituents, or both. Extracts with no added excipients or inert substances and no processing beyond the extraction are called native or genuine extracts.

          Production

          Herbal drugs, solvents and other materials used for the preparation of extracts are of suitable quality and where applicable comply with the requirements of any relevant monograph in the Pharmacopoeia. Where justified, herbal drugs used for the production of extracts may exceed the limits for heavy metals specified in the “Herbal Drugs” (Appendix 1.16H) provided that the resulting extract satisfies the requirements for heavy metals (Appendix 5.2).
           Different batches of the herbal drug which are compliant with the relevant monograph, or in the absence of an individual monograph with other suitable specifications, may be combined prior to extraction to achieve a certain range of content for one or more constituents in the herbal drug to be extracted. The herbal drug may also undergo a preliminary treatment, for example, grinding, inactivation of enzymes or defatting. In addition, unwanted constituents
(e.g., toxic constituents) or unwanted matter (e.g., insoluble matter) may be removed at a suitable stage in the production process.  
           Where solvents are recovered from the production process, such recovered or recycled solvents may be used, provided that the recovery procedures are controlled and monitored to ensure that solvents meet appropriate standards before re-use or admixture with other approved materials. Water used for preparation of extracts is of suitable quality such as Purified Water.
           Where applicable, extraction liquors are concentrated to the intended consistency using suitable methods, usually under reduced pressure and at a temperature at which deterioration of the constituents is reduced to a minimum. Essential oils that have been separated during processing may be restored to the extracts at an appropriate stage in the production process. Suitable excipients or inert substances may be added at various stages of the production process for technological reasons (for example, as part of the drying process or to improve the homogeneity or consistency of an extract). For some extracts, suitable inert excipients may also be added to adjust one or more constituents to a defined content. Suitable inert substances may be added as carriers or diluents to improve physical characteristics. Suitable stabilizers, antioxidants, antimicrobials, and other preservatives may be added to preserve the integrity, where justified and authorized. 
            Extraction with a given solvent leads to a typical content of selected constituents in the extracted dry matter; during production of extracts, purification procedures may be applied that increase the content of these selected constituents with respect to the expected values; such extracts are called refined extract.
             Where applicable, as a result of analysis of the herbal or animal matter used for the production of extracts, tests for microbiological quality, heavy metals, aflatoxins, and pesticide residues in the extracts have to be carried out.  

             Pesticide residues Unless otherwise stated in the monograph, the extracts comply with the “Pesticide Residues” (Appendix 7.22H). Where justified, this test may be totally or partially exempt when the complete history (nature and quantity of the pesticides used, date of each treatment, during cultivation and after harvest) of the treatment of the batch is known and can be checked precisely and according to good agricultural and collection practice (GACP).

              Labelling  The label on the container states (1) the herbal or animal matter used; (2) whether the extract is liquid, soft, oleoresin, or dry; (3) the composition of the extraction solvent; (4) where applicable, that fresh herbal or animal matter has been used; (5) where applicable, that the extract is “refined”; (6) the name and amount of any excipient or inert substance used; (7) where applicable, that the content of constituents (markers) have been
used for quantification and (8) the range of starting material: final extract (Drug: Extract Ratio or DER).

Liquid Extracts

          Liquid extracts are liquid preparations of which, in general, one part by mass or volume is equivalent to one part by mass of the original dried herbal or animal matter. These preparations are adjusted, if necessary, so that they satisfy the requirements for content of solvent, and, where applicable, for constituents or dry residue.

         Production Liquid extracts are prepared using ethanol of a suitable concentration and/or water together with, where necessary, other substances to extract the herbal drug, or by dissolving a soft or dry extract of the herbal drug (which has been produced using the same extraction solvent as would be used to prepare the liquid extract by direct extraction) in either ethanol of the required concentration or water. 
          Liquid extracts produced from soft or dry extracts do not contain any excipients other than those that would be present in the liquid extract prepared by direct extraction. However, exceptions may be justified in certain cases such as when the soft extract used to produce the liquid extract contains stabilizers, antioxidants or antimicrobial preservatives that have been added to ensure its stability.
          Liquid extracts are adjusted, if necessary, so that they satisfy the requirements for content of solvent. Liquid extracts may be filtered, if necessary. A slight sediment may form on standing.

          Relative density Where applicable, the liquid extract complies with the limits prescribed in the monograph.

          Ethanol content For ethanolic liquid extracts, carry out the “Determination of Ethanol” (Appendix 6.5). The preparation complies with the limits prescribed in the monograph.

          2-propanol Not more than 0.05 per cent v/v of 2-propanol for ethanolic liquid extracts unless otherwise prescribed.

          Dry residue In a flat-bottomed dish about 50 mm in diameterand about 30 mm in height, introduce rapidly 2.0 g or 2.0 mL of the extract to be examined. Evaporate to dryness on a water-bath and dry at 105º for 3 hours. Allow to cool in a desiccator over self-indicating silica gel or other suitable desiccants and weigh. Calculate the result as a percentage or in grams per litre.

          Packaging and storage Liquid extracts shall be kept in well-closed containers, protected from light.

          Labelling The label on the container states in addition to the requirements listed above (1) where applicable, the ethanol in per cent v/v in the final extract; (2) the concentration of any added antimicrobial preservative.

Soft Extracts

          Soft extracts are semi-solid preparations obtained by evaporation of the solvent used for preparation. Soft extracts generally have a dry residue of not less than 70 per cent w/w. They may contain suitable antimicrobial preservatives.

          Dry residue In a flat-bottomed dish about 50 mm in diameter and about 30 mm in height, weigh rapidly 2.0 g of the extract to be examined. Heat to dryness on a water-bath and dry at 105º for 3 hours. Allow to cool in a desiccator over self-indicating silica gel or other suitable desiccants and weigh. Calculate the result as a percentage weight in weight. Where applicable, a monograph on a soft extract prescribes a limit test for the solvent used for extraction.

          Packaging and storage Soft extracts should be kept in tightly closed containers, protected from light.

          Labelling In addition to the requirements listed above, the label on the container states the concentration of any added antimicrobial preservative.

Oleoresins

          Oleoresins are semi-solid preparations composed of a resin in solution in an essential and/or fatty oil and are obtained by evaporation of the solvent(s) used for their production.
          The following requirements apply to oleoresins produced by extraction and not to natural oleoresins.
          Water The oleoresin complies with the limits prescribed in the monograph.
          Packaging and storage Oleoresins shall be kept in tightly closed containers, protected from light.

Dry Extracts

          Dry extracts are solid preparations obtained by evaporation of the solvent used for their production. Dry extracts generally have a dry residue of not less than 95 per cent w/w.

          Loss on drying Where applicable, the dry extract complies with the limits prescribed in the monograph. In a flat-bottomed dish about 50 mm in diameter and about 30 mm in height,weigh rapidly 500 mg of the extract to be examined, finely powdered. Dry at 105° for 3 hours. Allow to cool in a desiccator over self-indicating silica gel or other suitable desiccants and weigh. Calculate the result as a percentage weight in weight. Where applicable, a monograph on a drug extract prescribes a limit test for the solvent used for extraction.

          Water Where a test for loss on drying is not applicable, the dry extract complies with the limits prescribed in the monograph.

          Packaging and storage Dry extracts should be kept in tightly closed containers, protected from light.

HERBAL TEAS

          Herbal Teas consist exclusively of one or more herbal drug(s) intended for oral aqueous preparations by means of decoction, infusion or maceration. They are usually supplied in bulk form or in sachets.

          Microbial limit Herbal Teas comply with the “Limits for Microbial Contamination” (Appendix 10.5), taking into account the prescribed preparation method (use of boiling or non-boiling water).

          Weight variation Determine the average weight of twenty randomly chosen units as follows: weigh a single full sachet of herbal tea, open it without losing any fragments. Empty it completely using a brush. Weigh the empty sachet and calculate the weight of the contents by subtraction. Repeat the operation on the nineteen remaining sachets. Unless otherwise justified not more than two twenty individual weights of the contents deviate from the average weight of the contents by more than the percentage deviation shown in the table below and none deviates by more than twice that percentage.

          Packaging and storage Herbal Teas should be kept in well-closed containers, protected from light.

TOPICAL PREPARATIONS

          Topical preparations are drugs intended for topical application in a wide variety of dosage forms.

          Minimum fill Topical preparations except plasters comply with the test described in the “Minimum Fill” (Appendix 4.26).

Topical Semi-Solid Preparations​

          Topical semi-solid preparations are intended to be applied to the skin or to certain mucous surfaces for local action or percutaneous penetration of medicaments, or for their emollient or protective action. They are of homogeneous appearance. Topical semi-solid preparations consist of a simple or compound base in which, usually, one or more active substances are dissolved or dispersed. According to its composition, the base may influence the action of the preparation and the release of the active substance(s).

          The bases may consist of natural or synthetic substances and may be single-phase or multi-phase systems. According to the nature of the base the preparation may have hydrophilic or hydrophobic (lipophilic) properties; it may contain suitable additives such as antimicrobial preservatives, antioxidants, stabilizers, emulsifiers and thickeners.

          If a preparation is specifically intended for use on large open wounds or on severely injured skin, it should be sterile. Preparations required to be sterile must comply with the test for sterility.

          If the particle size of the ingredients is of importance for the therapeutic purpose of a topical semi-solid preparation, the test to be applied should be specified.

          Topical semi-solid preparations can be distinguished into four categories: (1) creams (hydrophobic or hydrophilic); (2) gels (hydrophobic or hydrophilic); (3) ointments (hydrophobic, water-emulsifying or hydrophilic); (4) pastes.

           Sterility Where the preparation is labelled as sterile and unless otherwise directed in the individual monograph, it complies with the “Sterility Test” (Method I, Appendix 10.1).

           Packaging and storage Topical semi-solid preparations should be stored in well-closed containers or, if the preparation contains water or other volatile constituents, in a tightly closed container. The containers are preferably collapsible metal tubes from which the preparation may be readily extruded. Other types of container may be used. Containers for preparations for nasal, aural, vaginal, or rectal use should be adapted to deliver the product to the site of application or should be accompanied by a suitable applicator. They should be stored at a temperature not exceeding 30º unless otherwise prescribed. For creams and gels, they shall not be frozen.

           Labelling The label of topical semi-solid preparations states (1) the name and concentration of any added antimicrobial preservative(s); (2) where applicable, that the preparation is sterile.

          CREAMS Creams are homogeneous, semi-solid preparations consisting of opaque emulsion systems. They are multiphase preparations composed of a lipophilic phase and an aqueous phase.

           Hydrophobic creams Hydrophobic creams have the lipophilic phase as the continuous phase. They contain water-in-oil emulsifying agents such as wool fat, sorbitan esters and monoglycerides.

           Hydrophilic creams Hydrophilic creams have the aqueous phase as the continuous phase. They contain oil-in-water emulsifying agents such as sodium or triethanolamine soaps, sulfated fatty alcohols and polysorbates, combined, if necessary, with water-in-oil emulsifying agents.

          GELS Gels are usually homogeneous, clear, semi-solid preparations consisting of a liquid phase within a three-dimensional polymeric matrix with physical or sometimes chemical cross-linkage by means of suitable gelling agents.

           Hydrophobic gels Hydrophobic gel (oleogel) bases usually consist of liquid paraffin with polyethylene or fatty oils gelled with colloidal silica or aluminium or zinc soaps.

          Hydrophilic gels Hydrophilic gel (hydrogel) bases usually consist of water, glycerol, or propylene glycol gelled with suitable agents such as tragacanth, starch, cellulose derivatives, carboxyvinyl polymers and magnesium aluminium silicates.