Acetylsalicylic acid suppositories

Scale (mg/suppository) Item Material Name Quantity/1000 Suppositories (g) 

Allow to cool to 40°C and add item 1 while stirring with a turbine mixer. 

Continue mixing and cooling and pour into molds at 35°C that were previously chilled to 0° to -5°C remove suppositories from molds after 7 minutes. 

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Irritation of the rectal mucosa occurs when large particles are used. A particle size of 180 pm should therefore be the maximum. Irritation of the mucosa may also occur when small particles of an irritating active substance dissolve (too) quickly. This happens for instance when acetylsalicylic acid with a particle size of 45 pm is used in suppositories. It has a fast release of the active substance from the suppository and it dissolves rapidly, but as a result it irritates the mucosa. Therefore acetylsalicylic acid should be used with a particle size of 180 pm. 

Taking into account the mentioned loss of mass and possible content variation. Table 11.11 presents the required excess of suppositories for increasing batch sizes. This table is based on relatively fast settling substances such as acetylsalicylic acid (180) and cyclizine hydrochloride (180). For instance in paracetamol (45) the content variation... 

The validation of a new suppositoiy formulatimi wUl bring about the determination of the cmitent uniformity of a number of batches. Consequently, this deteiminatimi is also necessary if the preparation method is changed. For a process validation, and probably persmmel qualificatimi, of the preparatimi of suspension suppositories in general, acetylsalicylic acid is a good test substance. Acetylsalicylic acid (180) settles easily and is also easy to analyse in suppositories. 

The hydroxyl value is a measure of the number of acylable places and thus the content of mono-and diglycerides. A suppository base (Hard fat) with a low hydroxyl value (<15) is less damaging to the stability of acetylsalicylic acid and ergotamine tartrate than bases with a higher hydroxyl value. Witepsol H15 has a sufficiently low hydroxyl value (5-15) for this preparation. Bases with a high hydroxyl value (up to 50) have a better emulsifying ability and can include aqueous systems in the form of a water-in-oil-emulsion. 

The preparation instructiOTi of standardised individual preparations is validated beforehand. For non-standardised preparations this is not the case, and therefore it is advisable to validate the preparation template of the relevant dosage forms. By choosing a model preparation for each combination of dosage form and method of preparation the validation can be performed. It is not necessary to prepare the model preparation in daily practice. An example is the validation of the manual preparation of suspension suppositories. Suppositories with acetylsalicylic acid 100 mg can serve as a model preparation, because the equal distribution of the active ingredient in this product is difficult (see Sect. 11.5.2). By scheduling the model preparations in a periodic cycle, this validation can be coupled to the permanent qualification of personnel. 

Active substance should be rather troublesome to process but doesn t need to be practically relevant (for instance acetylsalicylic acid in suppositories hydrocortisone acetate to be dispersed in a cream base saHcyhc acid to be dispersed in white soft paraffin). 

The insolubility of acetylsalicylic acid is a contributing factor to its irritant action on the gastric mucosa it is hydrolysed in aqueous solution. It has, however, been incorporated in a suppository base with macrogols 1540 and 6000 which increase its solubility and appear to improve the absorption of the drug [198]. 

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