ISO 23419-2021 pdf free download – Traditional Chinese medicine — General requirements for manufacturing procedures and quality assurance of granules.
4.6Granulation
4.6.1 General
a)Intermediates (dry extracts) can be crushed to obtain a powdery substance if necessary,to
homogenize with diluents, binders, disintegrants or other excipients.
b) Only authorized pharmaceutical excipients described in pharmacopoeias or other official
documents shall be used.
c) The resulting powder is granulated by, for example, dry or semi-dry granulation, wet granulation
or compaction.
NOTE1 Among many excipients used for pharmaceutical products, starch, lactose,maltose, sucrose,dextrin and maltodextrin are frequently used diluents for granules or compactates made from medicinalplants.They are cost-effective and their binding abilities are generally good.
d) The particle size range of granules and compactates for herbal medicine shall be 0,18 mm to
4,0 mm.
NOTE 2 Specified particle size range varies among pharmacopoeia in each country (see Annex B).4.6.2 Dry granulation
a)Granules can be obtained from agglomerated substance prepared by the dry granulation method.b) Blend homogeneously extract powder and excipients such as diluents, binders, disintegrators or
other authorized excipients, and then directly compress with a lubricant into agglomerates or slagtablets by appropriate technics such as a dry granulator or tableting machine.
NOTE These agglomerates or tablets are milled into granules by appropriate mill or crushing apparatus.c)Obtained granules are sieved to give a desired range of particle sizes.
d)In this process,the critical parameters are as follows:
1) dry granulator
– uniformity of mixing (pre-mixing time, post-mixing time, min);-screw rotation speed (r/m);
— rotation speed (r/m);
— roller pressure (kPa);
— temperature (°C);
2) tableting machine
— uniformity of mixing (pre-mixing time, post-mixing time, min);
— disc rotation speed (r/m);
— tableting pressure (kPa);
— temperature (°C);
e) granulation and sieving
— first pass yield (%);
— particle size distribution (μm).
4.6.3 Semi-dry granulation
a) A small amount of water or other solvents, usually less than 5 % (1 % to 4 %, preferably), is added to a mixture of dry extract powder and excipients such as diluents and binders, then mixed.
b) The moistened mixture is granulated with, for example, a device equipped with two shafts extruder and screen for classification.
c) Residual water or solvents are removed by heating to obtain dry granules.
d) In this process, the critical parameters are as follows:
1) uniformity of mixing;
2) type of solvent added and residual solvent content (%);
3) amount of solvent added (%);
4) drying temperature (°C);
5) drying duration (h);
6) residual solvents content (%);
7) water content (%);
8) particle size distribution (μm).
4.6.4 Wet granulation
a) Blend homogeneously extract powder and excipients such as diluents and binders, moisten with a
solvent, form into a desired shape and size and then dry.
b) Sieve the obtained granules to give desired range of particle size.
c) In this process, the critical parameters are as follows:
1) uniformity of mixing;
2) kind of solvent added;
3) amount of solvent added (%);
4) drying temperature (°C);
5) drying duration (h);
6) particle size distribution (μm);
7) residual solvents content (%);
8) water content (%);
9) pressure (Pa).
4.7 Compaction
a) Compactates are obtained directly from the dried extract or herbal powder.
NOTE 1 Extract powder (possibly blended) and excipients such as diluents, binders, disintegrators or other authorized excipients are directly compressed with a roller compactor or a comparable technique to sheets and milled into irregular-shaped particles by an appropriate mill.
NOTE 2 These particles (compactates) are sieved to give the desired range of particle sizes.
b) In this process, the critical parameters are as follows:
1) uniformity of mixing;
2) type of excipients added;
3) rotation speed (r/m);
4) pressure (kPa);
5) temperature (°C);
6) particle size distribution (μm).ISO 23419 pdf download.